Ѯᢊϛॳᚂᇬ

Ҭȁᓃ 䫔 1 ⌟ 䫔 3㛇 2019 ⸜ 12 㚰

ࡾġġЕ

2019⎘䀋儎ᷕ桐⬠㚫朆䵕Ṿ␥K㊖㈿∹⎋㚵㈿ↅ埨∹䓐㕤⽫㇧举䵕栓≽か侭ᷕ桐 枸旚㱣䗪㊯⺽ 㜿晭⤪ˣ湫劙⹕ˣⲼ䘦曺ˣ哉≃↙ˣ挦剟厵ˣ悕㚠ⶮˣ⬳䡏⥵ˣ‭䵕ṩˣ ⽫㇧举䵕栓≽枸旚ᷕ桐㱣䗪㊯⺽ℙ嬀⮷䳬...... 143

ᆣġġ፣

㈿ↅ埨∹䚠斄⿏儎↢埨䘬喍䈑㱣䗪 昛⿅㰅ˣ㜿㫋₨ˣ哉≃↙...... 185

2019⸜8㚰⊿⋨儎ᷕ桐暁㚰㚫Highlight

㜄叔列ˣ昛⎛䶗ˣ昛㝷暾...... 194

ijıIJĺԑѮᢊသϛॳᏰོᏰ೚ंଆོ

㚫嬘嬘䦳...... 204

⸜㚫屜屻㺼嫃...... 212

⃒䥨婾㔯䋶⼿䋶⎵╖...... 213

⃒䥨婾㔯䋶㐀天...... 214

⡩⟙婾㔯㐀天...... 221 Formosan Journal of Stroke

Volume 1, Issue 3, DEC 2019 Contents

Guidelines

2019 Taiwan Stroke Society Guideline on the Use of Non-Vitamin K Antagonist Oral Anticoagulants for Prevention of Stroke in Patients with Atrial Fibrillation

Ya-Ju Lin, Ying-Ting Huang, Pai-Ching Tsui, Li-Kai Tsai, Chih-Ping Chung, Shu-Fan Kuo, Pi-Shan Sung, Helen L. Po, Taiwan Stroke Society Guideline Consensus Group...... 143

Review Articles

Medication Treatment in Anticoagulant-Associated Intracerebral Hemorrhage

Szu-Ju Chen, Shin-Yi Lin, Li-Kai Tsai...... 185

Northern Taiwan Bimonthly Stroke Meeting Highlight

Wanliang Du, Yu-Wei Chen, Po-Lin Chen...... 194

2019 Annual Meeting of Taiwan Stroke Society

Meeting Programs...... 204

Plenary Lecture...... 212

Excellent Paper Winners...... 213

Abstracts of Excellent Papers...... 214

Abstracts of Poster Papers...... 221 ၗޟߝٱ౩

჏က୷࿎௲ᙴଣᆶߏ۪ᙴଣᖐՉǴ೭ࢂܭҁԃ11Д22-24Вܭ2019ԃѠ᡼တύ॥ԃ཮ஒ ځεࠠᏢೌࢲ୏Ƕၸ۳Ǵတύ॥ԃ཮ନΑ2011ԃමӧᄆϯᖐՉǴޑᏢ཮ಃ΋ԛӧ჏ကᖐՉ ཀကᆶ੝ՅǴ΋Бय़ࢂတύڀ೿཮୔ᖐՉǴϞԃӧ჏ကᖐՉǴձޑдԃ཮೿ӧчǵύǵଯ Ҟ኱Ƕќ΋Бޑගϲύ॥ݯᕍࠔ፦ǵᕭλࠤໂৡຯࢂᏢ཮ޑǴӄय़ז຾৖ᡂϯࡐޑ॥ບᕍ ѬᙴଣᏢಞǶϞځԋ݀Ǵॶளޑ΢Ǵၸѐ൳ԃԖ࣬྽ӳزᙴৣॺӧύ॥ບᕍᆶࣴޑय़჏ࠄ ᆶߏයྣៈ฻നཥЪ܄යບᘐᆶݯᕍǵ٥࡚܄ଣࡕࢬำǵ࡚ډ࿯Ҟ఼ᇂԾଣ߻௱ៈǵޑԃ ᔈҔǵՈਵ౽ନπբ֝฻Ǵϣ৒ᆒߍǴॶள೭Βǵޑ૸ፕǴΨхࡴΓπඵችӧύ॥ޑ᏾ֹ ೭ᙴᏢ៟৏ᆶӧӦ॥௃Ǵᆃ၈៿߆ாኘϧᆿᖏୖуǶڙΟВӧ჏ကӳӳ٦

ᙣઔ ε཮ԋф Ѡ᡼တύ॥Ꮲ཮౛٣ߏ

ལᗎ

2019ԃ11Д22В

Welcome Message

Dear Colleagues, The 2019 Taiwan Stroke Society (TSS) Annual Meeting will be held at Chiayi Christian Hospital and Chiayi Chang Gung Memorial Hospital from November 22th (Friday) to 24th (Sunday), 2019. This is the first large stroke academic event held in Chiayi. In the past, except for one TSS annual meeting held in Changhua in 2011, the other annual meetings were held in the Taipei, Taichung, and Kaohsiung cities. This year’s meeting in Chiayi has important features. The progress of stroke diagnosis and treatment is fast, and to narrow the gap between urban and rural areas in stroke management is important. Furthermore, excellent performance in stroke management and research by stroke specialists in Chiayi and Tainan is commendable. This meeting's program covers from pre-hospital emergency services, acute phase diagnosis and treatment, post-acute care and long- term care, as well as artificial intelligence in stroke applications, thrombectomy workshops, etc. It is worthwhile to enjoy this medical feast and local style in Chiayi. We sincerely anticipate your attendance. Sincerely yours

President, Taiwan Stroke Society November 22, 2019 σོкৰޟၗ

ӚՏᙴৣǵ஑ৎǵᏢޣϷӃ຾ ໋᠙

៿߆ୖу2019ԃѠ᡼တύ॥Ꮲ཮ԃ཮Ǵҁԛԃ཮ஒܭ2019ԃ11Д22ВԿ24Вܭ჏ကᖐ ΓϯᙴᕍϝԖࡑঁޑ຾৖ǴฅԶଞჹύ॥ੰΓޑݯᕍԖ࣬྽ӭޑՉǶӧၸѐ೭΋ԃǴύ॥ ոΚǶӧԜǴᙣж߄ԃ཮ᝢഢ཮ǴགᖴੇϣѦ܌Ԗୖᆶޑ຦ᇯǶϞԃޑ࿯ҞନΑхࡴύ॥ ࡕයϷߏයྣៈ܄ݯᕍǵ࡚܄ଣ߻ύ॥ᒣ᛽ǵύ॥ቹႽᔠࢗǵ࡚ډӵٯ᏾ၸำǴֹޑៈྣ ୀෳᆶೀ࿼ǵү՟ޑύ॥ёૈٰྍ܄ӵଞჹਵηٯЬᚒǴޑჴҔ׳ܭ჋၂ᆫข׳ॺךѦǴ ޑᙴᏢϐ҂ٰǶགᖴாܭॺΨ߃௖ΓπඵችᔈҔךບᘐǶԜѦǴޑࠠ߄౜ڂύ॥ᆶύ॥ό ԏᛘǶޑᆶ٠׆ఈாԖᅈᅈୖ

ᡏ଼ந ࿤٣ӵཀي ᙣઔ

2019ԃ11Д22В

Dear friends and colleagues,

Welcome to the 2019 Annual Meeting of Taiwan Stroke Society, which will take place in Chiayi on November 22 to 24, 2019. Over the past year, there have been many exciting advances in the treatment of stroke. However, we are way behind when it comes to delivering personalized medicine to patients with stroke. On behalf of the organizing committee, I would like to thank all guest speakers and moderators from overseas and all the attendees. The 2019 program includes the full continuum of stroke care such as prehospital stroke identification, imaging of stroke, acute treatment, post-acute and long-term care. Moreover, we try to organize a meeting to focus on more down-to- earth topics such as detection and management of embolic stroke of possible sources and diagnosis of stroke mimics and chameleons. We also take a glimpse into the future of artificial intelligence in medicine. Thank you for joining us for this event and we hope you enjoy this meeting.

Sincerely yours,

November 22, 2019 ϛॳႱ٩ݽᕛࡾЕޱᡊᆰᠬଢ଼௉ܘᏗՖᏘҢܻЖתᏘο݈תŌࡼڼࡾġġЕ ߨᆰт

ᏗՖתᏘο݈תŌࡼڼijıIJĺѮᢊသϛॳᏰོߨᆰт ϛॳႱ٩ݽᕛࡾЕޱᡊᆰᠬଢ଼௉ܘᏘҢܻЖ

4ǵۇ໡ӵ1ǵ໳म৥1ǵஞԭߙ1ǵጰΚഩ2ǵᗛ߀๩3ǵ೾ਜԁ1ǵֺᅸ݅ ᠼᆢ᠞୏Ⴃٛύ॥ݯᕍࡰЇӅ᛽λಔ܊ഡᆢϘ1, 5ǵЈ

ᙴଣઓ࿶ࣽۺଭିइ 1 2Ѡεᙴଣઓ࿶೽ᄤတύ॥ύЈ 3Ѡчᄪ҇ᕴᙴଣઓ࿶ᙴᏢύЈઓ࿶ϣࣽ 4ԋεᙴଣઓ࿶೽ ᙴଣတύ॥ύЈۺ5ଭିइ

(ࠉȁȁِ 䓐㈿ↅ埨∹⮶农♜慵↢埨䘬桐晒⍲嗽伖烊(5 AFか侭䈡⭂冐⸲䉨㱩䘬嗽伖烉⊭⏓⸜攟侭ˣ㆟ ⽫㇧举䵕栓≽(atrial fibrillation, AF)㗗⮶农 ⫽ˣら⿏儓䗌ˣ⎰Ἕ偅冇䕦䕭ˣ僶冇䕦䕭⍲≽ 仢埨⿏ᷕ桐㚨慵天䘬⌙晒⚈⫸ᷳᶨ炻ḇ㗗䚖⇵ 傰䱍䉨䠔⊾/栙埨䭉䊡䨬䫱烊(6) ἧ䓐NOACs 䘬 䁢㬊炻傥⣈㚱㓰ẍ⎋㚵㈿ↅ埨∹喍䈑ἄ䁢⇅䳂 㲐シḳ枭(⏓喍䈑ṌḺἄ䓐ˣ忚埴Ὕℍ⿏㩊㞍ㆾ 枸旚(primary prevention)䘬冐⸲䉨㱩ˤ娛䳘䘬 ㇳ埻䘬 喍冯ℵ䓐喍㗪㨇ᷳ⺢嬘䫱)ˣ⁛䴙⎋㚵 䚠斄㱣䗪㊯⺽⶚㕤2012⸜䘤Ự炻᷎㕤2016⸜㚜 ㈿ↅ埨∹冯NOACsᷳ攻䘬廱㎃炻⍲䓐慷拗婌䘬 㕘ˤ㚱揹㕤⚃䧖朆䵕Ṿ␥K㊖㈿∹⎋㚵㈿ↅ埨 嗽䎮烊(7) ᶵ㖶⍇⚈ᷕ桐⍲⮵ᷕ桐か侭AF䘬” ∹(non-vitamin K antagonist oral anticoagulants, 㷔䫱ˤ NOACs)ᶲⶪẍἮ炻映临㚱䚠䔞⣂㕘䘬慓⬠⮎ 㛔㫉㊯⺽⮎嫱⺽䓐炻㟡㒂AHA/ACC/HRS 嫱屯㕁䘤堐炻㓭㚱㛔㫉㚜㕘ˤᷣ天㚜㕘⍇2016 ὅ⺢嬘ᷳ⻟⹎↮䁢Class IˣIIaˣIIbˣIII⍲ὅ嫱 ㊯⺽䫔⚃䪈䭨烉AFか侭㈿埨㞻㱣䗪ᷳ嫱㒂冯 㒂⑩岒↮䁢Level of Evidence (LOE) AˣB-Rˣ ⺢嬘炻冯䫔Ḽ䪈VKA (warfarin)冯NOACs䘬㭼 B-NRˣC-LDˣC-EOˤ 庫冯廱㎃悐↮ 墄⃭冯㓡⮓炻ᷣ柴⊭⏓ẍᶳ㔠 溆烉(1) 㖶䡢⭂佑䒋兄⿏冯朆䒋兄⿏⽫㇧举䵕 IJįġġᛞጰܒᇄߨᛞጰܒłŇ௉ޱ Ꮧתޟ栓≽炻᷎ὅ䄏か侭檀Ỷ桐晒Ⰼ䳂(high /low risk ଽճॳᓎቹ઻ຟե burden)䘬姽Ộ䴎Ḱ㈿ↅ埨喍䈑⺢嬘烊(2) ⚃䧖 Ֆ᛾ސ࡚ដ NOACs: dabigatran, rivaroxaban, apixaban and edoxaban 怑⭄∹慷䘬怠㑯冯⺢嬘烊(3) AFか侭 ⤪ỽ枸旚ℵᷕ桐(secondary stroke prevention)烉 IJįIJġġᛞጰܒᇄߨᛞጰܒłŇᅸဎϞᚄ ⊭⏓⿍⿏仢埨⿏ᷕ桐㗪䘬嗽伖ˣỽ㗪怑⎰攳⥳ ఼ ἧ䓐ㆾ䓐⚆⎋㚵㈿ↅ埨∹炻ẍ⍲劍㗗儎↢埨 ẍ⼨斄㕤AF⭡㖻忈ㆸ儎埨䭉㠿⠆⍲℞Ṿ ⼴炻ℵ䓐⎋㚵㈿ↅ埨∹䘬㗪㨇烊(4) AFか侭ἧ ℐ幓⿏㞻⠆ḳẞ炻⺢嬘ἧ䓐⎋㚵㈿ↅ埨∹Ἦ

忂妲ἄ侭烉‭䵕ṩ, 楔´䲨⾝慓昊儎ᷕ桐ᷕ⽫ E-mail: [email protected] DOI: 10.6318/FJS.201912_1(3).0001

143 ϛॳႱ٩ݽᕛࡾЕޱᡊᆰᠬଢ଼௉ܘᏗՖᏘҢܻЖתᏘο݈תŌࡼڼߨᆰт

枸旚䘬䚠斄䞼䨞炻䘮姣㖶䁢朆䒋兄⿏AF (non- ᷳ⇵㇨妶婾䘬炻2010⸜㍸↢䘬CHA2DS2VASc valvular AF, NVAF)ˤ忁ᾳ⎵娆Ụ᷶㊯㗗ᶵ傥㚱 score (0-9)㭼CHADS2 score (0-6)炻昌Ḯ庫Ἓ䘬 ảỽ⽫冇䒋兄䚠斄⓷柴炻Ữ⮎晃冐⸲䉨㱩᷎朆 㞻⠆ḳẞ枸㷔ᷳ⢾炻㚜傥⋨↮↢䛇㬋䘬Ỷ桐晒

⤪㬌炻⍵㖻忈ㆸ婌妋ˤ2016⸜㫸㳚⽫冇⬠㚫ᷳ か侭(CHA2DS2VASc score 0↮䘬桐晒䁢0.78%/

AF㱣䗪㊯⺽(ESC guideline for the management of Ṣ‒⸜炻⮵㭼CHADS2 score 0↮䘬桐晒䁢1.67%/ AF patients)ᷕ炻⌛ᶵℵἧ䓐Ⱦnon-valvular AFȿ Ṣ‒⸜) 6ˤ冒2016⸜⎬⚳䘬㱣䗪㊯⺽炻⊭㊔ 忁ᾳ⎵娆ˤ⛐⎬ᾳ䫔ᶱ㛇NOACs冐⸲娎槿䘬⍿ ESCˣCanadian guidelineˣ2018 ACCPˣNHFA

娎侭炻ṵ㚱役20%か侭⎰Ἕ㚱⎬⺷䒋兄⿏⽫冇 CSANZ䫱炻䘮⺢嬘ἧ䓐CHA2DS2VASc scoreἄ 䕭ㆾ㗗㚦 忶䒋兄ㆸ✳埻ㆾ㎃忶䓇䈑䒋兄炻⛐ 䁢➢㛔䘬姽Ộⶍ℟1-5, 7ˤ℞ᷕ⁛䴙ẍ1↮䁢ᷕ⹎

忁ṃか侭䘬㫉↮㜸栗䣢NOACsṵᾅ㚱䚠䔞䘬㓰 桐晒䘬㤪⾝炻⛐ἧ䓐CHA2DS2-VASc score㗪暨 㝄冯⬱ℐ⿏炻㇨ẍ⍵侴㗗ẌṢ㶟㵮䘬⎵䧙ˤ侴 天⮯⿏⇍⚈⫸䈡⇍㍸↢妶婾ˤ⛐㚨役䘬䞼䨞ᷕ ⼴2018 EHRAˣ2019 AHA/ACC/HRS㚜㕘䘬AF 䘤䎦炻晾䃞⤛⿏AFか侭㚱庫檀䘬ᷕ桐㭼䌯炻Ữ 㱣䗪㊯⺽炻悥ᶵℵἧ䓐non-valvular AF1-5ˤ䎦Ṳ ℞⮎忁桐晒㗗晐叿⸜䲨⡆≈(⯌℞㗗 ≥ 75㬚侭)ㆾ 䒋兄⿏AF (valvular AF)⮰㊯ᷕ⹎军慵⹎Ḵ⮾䒋 㗗⚈䁢⎰Ἕℑ䧖ẍᶲ䘬桐晒⚈⫸侴⡆≈䘬1, 6ˤ 䊡䨬(moderate to severe mitral stenosis炻⼰⎗傥 䔞⤛⿏AFか侭㰺㚱℞Ṿ䚠斄桐晒⚈⫸⬀⛐㗪

暨忚埴䒋兄ㇳ埻)⍲㨇㡘䒋兄(mechanical valve) (⤛⿏CHA2DS2VASc score 1↮)炻℞ᷕ桐桐晒冯 1-3 伖㎃侭 ˤ忁ṃか侭⺢嬘暨攟㛇ἧ䓐warfarin 䓟⿏(䓟⿏CHA2DS2VASc score 0↮)㗗ᶨ㧋䘬ˤ ᷎ᾅ㊩怑䔞䘬INRẍ㚱㓰枸旚埨䭉㞻⠆ˤ侴⮵ ⎗夳⤛⿏⎒傥䬿㗗AFか侭ᷕ桐桐晒䘬≈⻟⚈⫸ ℞ᷕ㨇㡘䒋兄伖㎃か侭(ᶵ⏓䓇䈑䒋兄ㆾ䒋兄 (risk modifier)ᶼ㗗冯⸜䲨䚠斄䘬(age-dependent) ㆸ⼊埻)䈡⇍⻟婧⺢嬘ἧ䓐VKA (warfarin)侴朆 侴朆䌐䩳䘬⌙晒⚈⫸2, 3, 6ˤ㇨ẍ⛐㫸伶㱣䗪㊯ NOACsㇵ傥䡢ᾅ㚱㓰枸旚儎㠿⠆䘬䘤䓇炻㟡 ⺽ᷕ炻斄㕤姽Ộᷕ桐/ℐ幓⿏㞻⠆ḳẞ炻劍䓟⿏

㒂RE-ALIGN trial (Randomized, Phase II Study CHA2DS2VASc score ≥ 2↮炻⤛⿏ ≥ 3↮炻夾䁢檀 to Evaluate the Safety and Pharmacokinetics of 桐晒烊䓟⿏ CHA2DS2VASc score 1↮炻⤛⿏2↮ Oral Dabigatran Etexilate in Patients After Heart 夾䁢ᷕ⹎桐晒1-3, 5ˤỮ㗗㟡㒂⎘䀋‍ᾅ屯㕁⹓䘬 8, 9 Valve Replacement)䘬䳸㝄栗䣢炻⛐ᷣ≽傰䒋ㆾ 䞼䨞 炻CHA2DS2VASc score 0-4䘬⎘䀋AFか侭 㗗Ḵ⮾䒋㨇㡘䒋兄伖㎃か侭ᷕἧ䓐dabigatran炻 䘤䓇ᷕ桐䘬㭼ἳ㖶栗檀㕤䐆℠䘬䘤䓇䌯炻䓂军

ℵᷕ桐⍲↢埨桐晒㖶栗檀㕤warfarin䳬ˤ侴 㗗CHA2DS2VASc score 0↮䘬⸜ᷕ桐䌯Ṏ⎗檀忼 rivaroxabanˣapixaban ẍ⍲edoxaban⯂䃉䚠斄䘬 1.1% (CHA2DS2VASc score 1侭䲬2.7%)炻⮵㕤⚳ 䞼䨞嫱㒂1ˤẍᶳ斄㕤NOACs䘬⺢嬘䘮㌺昌ᷕ慵 ṢAFᷕ桐枸旚喍䈑䘬怠㑯暨天㚜䧵㤝ヶ慵䘬侫 ⹎Ḵ⮾䒋䊡䨬⍲㨇㡘䒋兄伖㎃か侭ˤ ㄖˤ NOACs䚠斄冐⸲娎槿屯㕁栗䣢炻Ṇ㳚AF IJįijġłŇ௉ޱॳᓎቹ઻ޟຟե 㕷佌㭼朆Ṇ㳚㕷佌㚱㚜檀㭼ἳ䘬ᷕ桐/㞻⠆ḳẞ AFか侭桐晒Ⰼ䳂䘬姽Ộ㕡⺷炻ᶨ䚜㚱⼰⣂ 䘬桐晒炻ᶼἧ䓐warfarin↢埨ḳẞ㖶栗庫⣂9ˤ 䚠斄䘬䞼䨞冯䇕嬘炻昌ḮAF㛔幓⮶农䘬ⶎ⽫㇧ 侴⮎晃䓐㕤⎘䀋/Ṇ㳚⛘⋨䘬‍ᾅ屯㕁⹓屯㕁栗 㒜⣏冯埨㳩忇䌯㓡嬲䓊䓇䘬㞻⫸⢾炻㚜⣂㗗AF 䣢9-11炻ᶵ䭉㗗⛐仢埨⿏ᷕ桐䘬枸旚ˣ慵⣏↢埨 か侭ⷠ⎰Ἕ㚱⣂慵ℙ䕭(⤪檀埨⡻ˣ䱾⯧䕭ˣ 䘬䘤䓇炻ㆾ㗗栙ℏ↢埨䘬㭼ἳ炻NOACs悥㖶栗 ⅈ⽫䕭ˣ⽫堘䪕䫱)炻ἧ⼿ᷕ桐桐晒⣏䁢⡆≈ ⃒㕤warfarinˤ 6ˤ⎬桐晒⚈⫸䘬⼙枧䦳⹎ᶵᶨ炻⛐2012/2016 憅⮵AFか侭姽Ộ℞ᷕ桐冯↢埨桐晒⼴炻⮵ ⸜䘬⎘䀋儎ᷕ桐⬠㚫㊯⺽ᷕ⶚ 忶妶婾ˤ婈⤪ 㕤㈿ↅ埨喍䈑怠㑯䘬䵄⎰⺢嬘⤪ᶳ1-4烉

144 ϛॳႱ٩ݽᕛࡾЕޱᡊᆰᠬଢ଼௉ܘᏗՖᏘҢܻЖתᏘο݈תŌࡼڼߨᆰт

(1) CHA2DS2VASc score䓟⿏ ≥ 2↮ㆾ㗗⤛⿏ ≥ Evidence C)ˤ 3↮䘬AFか侭炻⺢嬘ἧ䓐⎋㚵㈿ↅ埨∹⊭ (8) ⽫㇧㑚≽ (atrial flutter)か侭炻⺢嬘㭼䄏AF ㊔烉warfarinˣdabigatranˣrivaroxabanˣ か侭桐晒姽Ộ炻ἧ䓐⎋㚵㈿ↅ埨∹(Class I, apixabanˣedoxaban (Class I, Level of Level of Evidence C)ˤ Evidence A)ˤ (9) ⭂㛇慵㕘姽Ộ AFか侭ᷕ桐冯↢埨桐晒炻 (2) 昌Ḯᷕ军慵⹎Ḵ⮾䒋䊡䨬ㆾ㨇㡘䒋兄伖 ẍ慵㕘㩊夾⎋㚵㈿ↅ埨∹ᷳ⽭天冯怠㑯 ㎃ᷳAFか侭⢾炻℞ṾAFか侭⺢嬘⃒⃰ (Class I, Level of Evidence C)ˤ

ἧ䓐NOACs (dabigatranˣrivaroxabanˣ (10) CHA2DS2VASc score䓟⿏1↮ㆾ⤛⿏2↮䘬 apixabanˣedoxaban) (Class I, Level of AFか侭炻ἧ䓐⎋㚵㈿ↅ埨∹枸旚ᷕ桐㞻 Evidence A)ˤ ⠆ḳẞ㗗⎰䎮䘬怠㑯(Class IIb, Level of

(3) ⺢嬘ẍ CHA2DS2VASc scoreἄ䁢AFᷕ桐 Evidence C-LD)ˤ 桐晒姽Ộ䘬㊯㧁(Class I, Level of Evidence (11) 昌朆㗗ᷕ军慵⹎Ḵ⮾䒋䊡䨬ㆾ㨇㡘䒋兄伖

B)ˤ ㎃⢾䘬AFか侭炻劍CHA2DS2VASc score䓟 (4) 㨇㡘䒋兄伖㎃䘬か侭⺢嬘ἧ䓐 warfarin ⿏0↮ㆾ㗗⤛⿏1↮炻⎗怠㑯ᶵἧ䓐⎋㚵㈿ (Class I, Level of Evidence B)ˤ ↅ埨∹(Class IIa)ˤ (5) ᶵ婾㗗ỽ䧖⼊⺷䘬 AF (paroxysmalˣ ᒵޟpersistentˣpermanent)炻㈿ↅ埨∹䘬怠㑯 ijįġġѲᆍŏŐłńŴᎌۣᏘ໔ 㗗ὅᷕ桐㞻⠆桐晒侴⭂(Class I, Level of ᐅᇄ࡚ដġ Evidence B)ˤ (6) ἧ䓐 NOACs⇵ㅱ⃰姽Ộか侭䘬偅僶≇傥炻 ⺢嬘军⮹㭷⸜㩊槿偅僶≇傥ᶨ㫉(Class I, ijįIJġġŏŐłńŴհҢᐠᙽᇄ᛾ސфᗂ Level of Evidence B-NR)ˤ ĩ୤َߒIJĪ (7) 怠㑯ἧ䓐⎋㚵㈿ↅ埨∹㗪炻ㅱὅか侭ᾳ⇍ 䉨㱩姽Ộ婒㖶䙲嗽冯↢埨桐晒炻⮲慵℞冒 ijįijġġᇄŸŢųŧŢųŪůࣺШӨŏŐłńŴޟਝ ಛޟၐᡛחӵӨᖝܒᇄԊӒݎ ᷣシ栀炻᷎冯䕭Ṣ/⭞Ⱄℙ⎴㰢⭂㱣䗪䘬㕡 ॎၥਟĩ୤َߒijĪ ⎹(shared decision making) (Class I, Level of

堐1ˢNOACsἄ䓐㨇廱冯喍䈑ẋ嫅

喍䈑䈡⿏ Dabigatran Rivaroxaban Apixaban Edoxaban 喍䎮ἄ䓐㧁䘬 䫔Ḵ⚈⫸ 䫔⋩⚈⫸ 䫔⋩⚈⫸ 䫔⋩⚈⫸ ⇵槭喍䈑 㗗 ⏎ ⏎ No⏎ 㚵䓐㕡⺷ ᶨ⣑ℑ㫉 ᶨ⣑ᶨ㫉 ᶨ⣑ℑ㫉 ᶨ⣑ᶨ㫉 䓇橼⎗䓐䌯 6% 80% 60% 62% ⋲堘㛇 12-17 ⮷㗪 5-13⮷㗪 9-14⮷㗪 10-14⮷㗪 僶冇⹻㶭䌯 80% ~33% ~27% ~50% 埨ᷕ㚨檀㽫⹎ 3⮷㗪 2-4⮷㗪 3-4⮷㗪 1-2⮷㗪 喍䈑ṌḺἄ䓐 P-gp inhibitors Strong inhibitors of Strong inhibitors of P-gp inhibitors CYP3A4 and p-gp CYP3A4 and p-gp 晐梸㚵䓐⏠㓞䌯 㰺㚱⼙枧 ⡆≈39% 㰺㚱⼙枧 ⡆≈6-22% 晐梸㚵䓐ᷳ⺢嬘 ᶵ⺢嬘 ⽭枰晐梸㚵䓐 ᶵ⺢嬘 ᶵ⺢嬘 CYP3A4, intestinal cytochrome P450 3A4; P-gp, P-glycoprotein.

145 ϛॳႱ٩ݽᕛࡾЕޱᡊᆰᠬଢ଼௉ܘᏗՖᏘҢܻЖתᏘο݈תŌࡼڼߨᆰт

堐2ˢ冯warfarin䚠㭼⎬NOACs䘬㓰㝄冯⬱ℐ⿏⛐⎬冐⸲娎槿䘬䴙妰屯㕁

NOAC Warfarin Dabigatran Dabigatran Warfarin Rivaroxaban Warfarin Apixaban Warfarin Edoxaban Edoxaban 150 mg 110 mg 60 mg 30 mg ḳẞ⸜ ḳẞ⸜ ḳẞ⸜ ḳẞ⸜ ḳẞ⸜ ḳẞ⸜ ḳẞ⸜ ḳẞ⸜ ḳẞ⸜ ḳẞ⸜ 䘤䓇䌯 䘤䓇䌯 䘤䓇䌯 䘤䓇䌯 䘤䓇䌯 䘤䓇䌯 䘤䓇䌯 䘤䓇䌯 䘤䓇䌯 䘤䓇䌯 %/year %/year %/year %/year %/year %/year %/year %/year %/year %/year ᷕ桐冯 1.72 1.12 1.54 2.40 2.10 1.60 1.27 1.80 1.57 2.04 ℐ幓⿏ 㞻⠆ḳẞ 仢埨⿏ 1.22 0.93 1.34 1.42 1.34 1.05 0.97 1.25 1.25 1.77 ᷕ桐 ↢埨⿏ 0.38 0.10 0.12 0.44 0.26 0.47 0.24 0.47 0.26 0.16 ᷕ桐 ⽫倴㠿⠆ 0.64 0.81 0.82 1.12 0.91 0.61 0.53 0.75 0.70 0.89 慵⣏↢埨 3.61 3.40 2.92 3.45 3.60 3.09 2.13 3.43 2.75 1.61 ḳẞ 儎↢埨 0.77 0.32 0.23 0.74 0.49 0.80 0.33 0.85 0.39 0.26 儠偫忻 1.09 1.60 1.13 1.24 2.00 0.86 0.76 1.23 1.51 0.82 ↢埨

သϛॳܒીՖܒࡨޱ௑ݷĩ୤ ĴįġġłŇ௉ޟҢٺijįĴġġŏŐłńŴ໸෵໔ ߒĴĪġ Ϟ೎ညَ

堐3ˢNOACs枰㷃慷ἧ䓐䘬ね㱩

Dabigatran Rivaroxaban Apixaban Edoxaban

CrCl 30-49 110 mg 15 (20) mg 5 mgᶨ⣑ℑ㫉 30 mg mL/min ᶨ⣑ℑ㫉 ᶨ⣑ᶨ㫉 2.5 mgᶨ⣑ℑ㫉 ᶨ⣑ᶨ㫉 劍ẍᶳảℑᾳ㡅ẞ⬀⛐: ⸜漉≥ 80㬚 橼慵≤ 60 kg Creatinine ≥ 1.5 mg/dL

CrCl 15-30 ᶵ⎗ἧ䓐 10 mg 2.5 mg 30 mg mL/min ᶨ⣑ᶨ㫉 ᶨ⣑ℑ㫉 ᶨ⣑ᶨ㫉

CrCl < 15 ᶵ⎗ἧ䓐 ᶵ⎗ἧ䓐 ᶵ⎗ἧ䓐 ᶵ⎗ἧ䓐 mL/min

儠偫忻↢埨 110 mg 5 mgᶨ⣑ℑ㫉 60 mgᶨ⣑ᶨ㫉 ᶨ⣑ℑ㫉 2.5 mgᶨ⣑ℑ㫉 劍ẍᶳảᶨ㡅ẞ⬀⛐, 劍ẍᶳảℑᾳ㡅ẞ⬀⛐: ∹慷暨㷃⋲: ⸜漉≥ 80㬚 橼慵≤ 60 kg 橼慵≤ 60 kg CrCl: 15-50 ml/min Creatinine ≥ 1.5 mg/dL ⎴㗪ἧ䓐P-gp inhibitor

⸜漉 > 75 110 mg 15 (20) mg 5 mgᶨ⣑ℑ㫉 60 mgᶨ⣑ᶨ㫉 ᶨ⣑ℑ㫉 ᶨ⣑ᶨ㫉 2.5 mgᶨ⣑ℑ㫉 劍ẍᶳảᶨ㡅ẞ⬀⛐, 劍ẍᶳảℑᾳ㡅ẞ⬀⛐: ∹慷暨㷃⋲: ⸜漉≥ 80㬚 橼慵≤ 60 kg 橼慵≤ 60 kg CrCl: 15-50 ml/min Creatinine ≥ 1.5 mg/dL ⎴㗪ἧ䓐P-gp inhibitor

146 ϛॳႱ٩ݽᕛࡾЕޱᡊᆰᠬଢ଼௉ܘᏗՖᏘҢܻЖתᏘο݈תŌࡼڼߨᆰт

AFか侭䘤䓇⿍⿏⽫⚈⿏ᷕ桐ᷳ⼴䘬2忙 䗪㓰㝄炻䳸㝄䘤䎦ℑ侭⛐14⣑ℏ仢埨⿏ᷕ桐⽑ ℏ炻⭡㖻⚈䁢埨㞻㞻⠆侴ℵ⹎ᷕ桐炻㖑㛇䘬奨 䘤䘬㨇䌯䚠Ụ(8.5%㭼7.5%)炻⛐䕯䉨⿏儎↢埨 ⮇⿏䞼䨞⟙⏲栗䣢炻䘤䓇㨇䌯䲬10-20%12炻晾 䘬㨇䌯ḇ䚠Ụ(2.7%㭼1.8%)炻ℑ䳬か侭⛐3ᾳ㚰 䃞役㛇䘬䞼䨞䘤䎦炻⿍⿏㛇ℵ䘤䌯⶚㖶栗旵Ỷ ⼴䘬㬣ṉ䌯炻冯䓇㳣ὅ岜䦳⹎ḇ㰺㚱㖶栗ⶖ䔘 军3.9%13炻Ữṵ庫℞Ṿ朆⽫⚈⿏ᷕ桐䘬ℵ䘤䌯 (66%㭼65%)ˤ 檀ˤ侴ᶼ⚈䁢⽫⚈⿏ᷕ桐⭡㖻⎰Ἕ㠿⠆⼴↢埨 2007⸜䘬ᶨ䭯䲣䴙⿏⚆栏冯䴙⎰↮㜸䘬䞼 (hemorrhagic transformation)䘬Ἕ䘤䕯14炻ℵ≈ᶲ 䨞(⊭⏓7ᾳ晐㨇冐⸲娎槿)㊯↢炻劍㗗⛐仢埨⿏ 䞼䨞㊯↢㖑㛇ἧ䓐㈿ↅ埨∹炻⎗傥冯䕯䉨⿏儎 ᷕ桐⼴䘬48⮷㗪ℏἧ䓐㛒↮⊾偅䳈(UFH)ˣỶ ↢埨ㆾ㗗㠿⠆⼴↢埨䚠斄15, 16ˤ㓭ᶨ凔侴妨炻 ↮⫸慷偅䳈(LMWH)ㆾ栆偅䳈(heparinoids)炻␴ ㈿ↅ埨∹⛐AFか侭⿍⿏ᷕ桐㱣䗪ᶲ䘬奺刚炻ṵ aspirinㆾ⬱ㄘ∹ 㭼庫炻䳸㝄䘤䎦㖑㛇ἧ䓐㈿ ⬀⛐姙⣂䇕嬘ˤ䚖⇵᷎㰺㚱晐㨇冐⸲䞼䨞屯㕁 ↅ埨∹ᶵ傥㷃⮹仢埨⿏ᷕ桐䘬⽑䘤䌯炻Ữ㚫⡆ ⺢嬘AFか侭䘤䓇⿍⿏仢埨⿏ᷕ桐ᷳ⼴炻ỽ㗪㗗 ≈儎↢埨䘬桐晒炻侴ᶼ㬣ṉ䌯ㆾ农㭀䌯᷎㰺㚱 攳⥳ἧ䓐⎋㚵㈿ↅ埨∹䘬怑䔞㗪㨇炻⓷柴䘬斄 㷃⮹20ˤ䚠⮵Ἦ婒炻℞Ṿ⮷✳䞼䨞栗䣢炻㖑㛇 挝⛐㕤埨㞻㞻⠆䘬⽑䘤冯⎗傥↢埨䘬桐晒␴⇑ ἧ䓐VKA (⛐ᷕ桐⼴䫔ᶫ⣑忼⇘㱣䗪㓰㝄)炻㚱 䙲姽Ộᶵ㖶ˤ伶⚳AHA/ASA guidelines⺢嬘⛐ 庫Ỷ䘬仢埨⿏ᷕ桐⽑䘤䌯炻傥㷃⮹㬣ṉ䌯␴农 仢埨ᷕ桐䘤䓇⼴䘬4-14⣑攳⥳㚵䓐⎋㚵㈿ↅ埨 㭀䌯炻侴ᶼ㰺㚱⡆≈儎↢埨䘬䘤䓇21-24ˤ℞Ṿ奨 ∹炻Ữ憅⮵㠿⠆⼴↢埨䘬か侭炻⎗侫ㄖ⺞⼴⎋ ⮇⿏䘬䞼䨞㊯↢炻ἧ䓐LMWHἮ扄㍍(bridging) 㚵㈿ↅ埨∹䘬ἧ䓐17ˤ㫸㳚ESC guidelines䘬⮰ ⎋㚵㈿ↅ埨∹䘬㕡⺷炻㚫㚱庫檀䘬↢埨桐晒25- ⭞シ夳⇯㟡㒂ᷕ桐䦳⹎冯䚠斄桐晒Ἦ㰢⭂㚵䓐 28ˤ ⎋㚵㈿ↅ埨∹䘬㗪攻5ˤ 㔠䭯奨⮇⿏䘬䞼䨞栗䣢炻仢埨⿏ᷕ桐⼴䘬 14⣑ℏἧ䓐NOAC⎗傥㗗⬱ℐ䘬21, 25, 29, 30ˤ㖍㛔 䘬SAMURAI-NVAF䞼䨞㊯↢炻⛐ᷕ桐⼴⸛⛯ ޟϛॳܒીՖܒᏗՖᏘӵࡨתĴįIJġġ ݽᕛᜌᐃ 4⣑䘬㗪攻≈ᶲNOAC炻傥㓡┬䳸㝄ᶼ䃉㖑㛇 13, 18, 19 ⃰⇵䘬晐㨇冐⸲娎槿屯㕁 䳸㝄᷎ᶵ 儎↢埨31, 32ˤ⎎ᶨᾳ奨⮇⿏䘬䞼䨞RAF-NOAC 㓗㊩仢埨⿏ᷕ桐䘬AFか侭⛐⿍⿏㛇ἧ䓐㈿ↅ埨 ⊭⏓1,127⎵⿍⿏仢埨⿏ᷕ桐䘬AFか侭炻栗䣢 18 喍ˤInternational Stroke Trial 姽Ộ⮯役2叔⎵炻 ⛐仢埨ᷕ桐2⣑ℏ攳⥳㚵䓐NOAC䘬か侭炻℞ 48⮷㗪ℏ䘤䓇仢埨⿏ᷕ桐䘬か侭炻↮ㆸἧ䓐偅 ᷕ桐⽑䘤⍲儎↢埨䘬䵄⎰㨇䌯䁢12.4%烊⛐3军 䳈ˣaspirinˣℑ侭䘮ἧ䓐ㆾℑ侭䘮ᶵἧ䓐ℙ⚃ 14⣑ℏ攳⥳㚵䓐NOAC䘬か侭炻℞䵄⎰㨇䌯䁢 䳬ˤ℞ᷕ䘬18,451⎵か侭㚱䚠斄䘬⽫冇䭨⼳屯 2.1%烊⛐14⣑⼴攳⥳㚵䓐NOAC䘬か侭炻℞䵄 13 㕁炻䔞ᷕℙ㚱3,169⎵か侭 (䲬Ỽ17%)㚱AF炻 ⎰㨇䌯䁢9.1%33ˤ䚖⇵᷎䃉⣏✳晐㨇䘬NOAC䞼 ↮㜸忁ṃ℟㚱AF䘬⿍⿏仢埨⿏ᷕ桐か侭炻ἧ䓐 䨞㚱䲵ℍ仢埨⿏ᷕ桐⼴7-14⣑ℏ䘬か侭炻Ữ㚱 偅䳈冯⏎炻Ụ᷶⮵㕤ℑ忙⼴䘬㬣ṉㆾᷕ桐⽑䘤 ᶨᾳ⮷✳䘬晐㨇娎槿Triple AXEL㓞Ḯ195ỵ䘬 䘬⼙枧᷎䃉ⶖ⇍(11.7%㭼12.0%)ˤ⎎⢾炻偅䳈 AFか侭炻⛐庽⽖⿍⿏仢埨⿏ᷕ桐䘬Ḽ⣑ℏ炻晐 䘬ἧ䓐䘬䡢⎗ẍ旵Ỷ㕘䘬仢埨⿏ᷕ桐䘤䓇(2.3% 㨇↮惵ἧ䓐rivaroxabanㆾwarfarin炻䳸㝄䘤䎦ἧ 㭼4.9%)炻Ữ㗗⎴㗪ḇ⡆≈Ḯ↢埨⿏ᷕ桐䘬䘤䓇 䓐rivaroxabanㆾwarfarin䘬か侭炻℞ᷕ桐⽑䘤␴ (2.8%㭼0.4%)ˤ 儎↢埨䘬㨇䌯悥䚠Ụ炻Ữ㗗ἧ䓐rivaroxaban䘬 19 2000⸜䘬HAEST䞼䨞 炻䲵ℍ449⎵㚱AF か侭䘬ỷ昊⣑㔠庫䞕34ˤ 䘬⿍⿏仢埨⿏ᷕ桐か侭炻⛐ᷕ桐⼴30⮷㗪ℏ炻 2018⸜㫸㳚EHRA guidelines2 ⮵㕤⿍⿏仢埨 㭼庫ἧ䓐Ỷ↮⫸慷偅䳈dalteparinㆾaspirin䘬㱣 ᷕ桐ㆾTIA⼴炻ἧ䓐⎋㚵㈿ↅ埨∹㗪㨇䘬⺢嬘

147 ϛॳႱ٩ݽᕛࡾЕޱᡊᆰᠬଢ଼௉ܘᏗՖᏘҢܻЖתᏘο݈תŌࡼڼߨᆰт

⣏农冯2016⸜ESC guidelines䚠⎴炻Ữἧ䓐㗪㨇 (EudraCT, 2018-003859-38烊劙⚳)炻TIMING 㚜䁢⻰⿏烉TIA䘤䓇1⣑ẍ⼴炻侫ㄖἧ䓐⎋㚵㈿ (NCT02961348烊䐆℠) 炻ẍ⍲START ↅ埨∹烊庽⽖ᷕ桐䘤䓇3⣑ẍ⼴炻侫ㄖἧ䓐⎋㚵 (NCT03021928烊伶⚳)ˤㆸ㝄枸妰㕤2021⸜⼴ ㈿ↅ埨∹烊ᷕ⹎ᷕ桐䘤䓇6-8⣑ẍ⼴炻㌺昌㠿⠆ 映临䘤堐ˤ ⼴↢埨炻侫ㄖἧ䓐⎋㚵㈿ↅ埨∹烊♜慵ᷕ桐䘤 ᏗՖᏘתҢο݈ٺҐܖ䓇12-14⣑ẍ⼴炻㌺昌㠿⠆⼴↢埨炻侫ㄖἧ䓐⎋ Ĵįijġġཱིຨᘞ 㚵㈿ↅ埨∹(⚾1)ˤ昌㬌ᷳ⢾炻ㅱ侫慷℞Ṿ䚠斄 ޟłŇ௉ޱีҡࡨܒીՖܒϛॳ Ϟ೎ည 冐⸲桐晒Ἦ㰢⭂㗗⏎㍸㖑ㆾ⺞⼴ἧ䓐⎋㚵㈿ↅ 埨∹ˤ 伶⚳AHA/ASA guidelines17 ⺢嬘AFㆾ⽫㇧ ẍᶲ⺢嬘䘮䁢⮰⭞ℙ嬀シ夳炻䚖⇵㚱 㑚≽か侭炻䘤䓇ᷕ桐ᷳ⼴炻劍儎悐暣儎㕟Ⰼ䃉 㔠ᾳ⣏✳晐㨇⮵䄏冐⸲娎槿忚埴ᷕ炻㍊妶 ↢埨ᶼ䃉℞Ṿ䤩⽴䕯炻⛐4.5⮷㗪ℏ炻⎗侫ㄖ AF⮶农⿍⿏仢埨⿏ᷕ桐䘬か侭炻㖑㛇ㆾ㘂 朄傰㲐⮬埨㞻㹞妋∹rt-PA᷎军⮹⛐24⮷㗪ᷳℏ 㛇ἧ䓐NOAC䘬䳸㝄冯枸⼴炻↮⇍⤪ᶳ烉 ᶵ⎗㚵䓐ảỽ㈿埨㞻喍䈑ˤ劍㰺㚱㲐⮬rt-PA炻 ELAN (NCT03148457烊䐆⢓)炻OPTIMAS ⎗侫ㄖἧ䓐㈿埨⮷㜧喍䈑㱣䗪炻᷎ᶼὅか侭ᷕ

⚾1ˢ䵄⎰ 2016⍲2018⸜㫸㳚⽫冇⬠㚫㊯⺽⮵㕤⿍⿏仢埨⿏ᷕ桐/䞕㙓儎仢埨⼴ἧ䓐⎋㚵㈿ↅ埨∹䘬 㗪㨇㳩䦳⚾

148 ϛॳႱ٩ݽᕛࡾЕޱᡊᆰᠬଢ଼௉ܘᏗՖᏘҢܻЖתᏘο݈תŌࡼڼߨᆰт

桐䦳⹎⍲䚠斄桐晒⛐ᷕ桐⼴4-14⣑㓡䓐⎋㚵㈿ Dabigatran䚖⇵⶚㚱⮰Ⱄ䘬⍵廱∹ ↅ埨∹ἄ㫉䳂枸旚炻Ữ㗗憅⮵㠿⠆⼴↢埨䘬か idarucizumabˤ㟡㒂⽟⚳␴䲸大嗕䘬䕭ἳ⟙⏲ 侭炻⎗傥侫ㄖ⺞⼴⎋㚵㈿ↅ埨∹䘬ἧ䓐ˤ 栗䣢炻ἧ䓐dabigatran䘬⿍⿏仢埨⿏ᷕ桐か侭炻 ⛐㍍⍿idarucizumabᶼ姽Ộↅ埨≇傥ᷳ⼴炻IVT ⟙Ụ᷶㗗⎗⮎埴ᶼ⬱ℐ䘬36, 37ˤ侴⎘䀋䘬䕭ἳ ีޱłŇ௉ޟᏗՖᏘתҢο݈ٺĴįĴġġ ҡࡨܒીՖܒϛॳϞ೎ည ⏲栗䣢炻10ỵἧ䓐dabigatran䘬⿍⿏仢埨⿏ᷕ桐 㟡㒂ᷳ⇵䘬䞼䨞栗䣢炻ἧ䓐⎋㚵㈿ↅ埨∹ か侭炻⛐㍍⍿idarucizumab⼴忚埴IVT炻㚱3ỵ 䘬AFか侭炻仢埨⿏ᷕ桐䘬䘤䓇䌯ṵ䃞㚱㭷⸜ か侭↢䎦儎↢埨(2ỵ䃉䕯䉨炻1ỵ㚱䕯䉨⿏儎↢ 1-2%ˤ䔞㱣䗪ἧ䓐⎋㚵㈿ↅ埨∹⌣ᷕ桐䘬AFか 埨)38ˤ⚈㬌⮰⭞⺢嬘炻ἧ䓐dabigatran䘬⿍⿏仢 侭㗪炻慓ⷓ⽭枰天姽Ộか侭㚵喍枮⽆⿏炻ẍ⍲ 埨⿏ᷕ桐か侭炻⎗侫ㄖ⛐㍍⍿idarucizumab⼴ℵ 喍䈑䧖栆∹慷䘬怠㑯㗗⏎⎰䎮35ˤ昌㬌ᷳ⢾炻 㕥埴IVT9ˤ ㅱ娚天姽Ộ℞Ṿ⎗傥䘬ᷕ桐⍇⚈ˤ 㟡㒂䕭ἳ䲣↿⟙⏲㊯↢炻⛐埨ᷕNOAC喍 䈑㽫⹎庫Ỷ䘬か侭炻IVT⎗傥㗗⬱ℐ䘬40, 41ˤ⛐ Ңᓗ૕Ֆ੃ྙ၌ᏘųŵĮőłϞ 㝸ṃ㚵䓐NOAC䘬⿍⿏仢埨⿏ᷕ桐か侭炻䔞㚱ٺĴįĴįIJġġ ໶ ⎗月䘬NOAC㩊㷔㕡㱽⍰ᶵ俥婌㗪攻炻᷎ᶼ埨ٱݧཎ 㟡㒂2018⸜伶⚳AHA guidelines⺢嬘炻㚵 ᷕ喍䈑䘬㽫⹎< 30 ng/mL (㬌㽫⹎⍫侫ῤ㗗㟡㒂 䓐warfarin䘬か侭炻⛐仢埨⿏ᷕ桐䕯䉨䘤䓇3 ⮰⭞⺢嬘妪⭂炻㗗㊯⛐㚵喍崭忶4⮷㗪⼴㩊㷔 ⮷㗪ℏ炻劍㗗INR ≤ 1.7ㆾPTῤ < 15䥺㗪炻⎗忚 rivaroxabanˣapixabanˣㆾedoxaban䘬埨ᷕ喍䈑 埴朄傰埨㞻㹞妋㱣䗪(intravenous thrombolysis, 㽫⹎)炻⎗ẍ侫ㄖIVT42ˤ䚖⇵忁ᾳ䫾䔍䘬㓰㝄 IVT)炻劍㗗INR > 1.7⇯ᶵ⎗ἧ䓐ˤ ⍲⬱ℐ⿏怬暨天㚜忚ᶨ㬍䘬冐⸲娎槿ˤ⃀䭉⤪ ἧ䓐NOAC䘬か侭炻䘤䓇⿍⿏仢埨⿏ᷕ 㬌炻⎗月㓷デ⍰⾓忇䘬NOAC埨ᷕ喍䈑㽫⹎㩊 桐㗗⏎⎗忚埴IVT炻䚖⇵⯂㛒塓䡢娵Ữ⎗傥㗗 㷔㕡㱽⛐⎘䀋⯂㛒⺋㲃ἧ䓐ˤ劍㗗NOAC䘬ἧ 㚱⭛䘬17ˤ㟡㒂2018 EHRA guidelines炻IVTᶵ 䓐䉨㱩䃉㱽䡢娵(ἳ⤪⣙婆䕯䘬か侭炻䃉㱽䡢娵 ⎗ἧ䓐㕤⇵㫉㚵䓐NOAC㗪攻⮷㕤24⮷㗪䘬か ⇵㫉㚵䓐NOAC䘬㗪攻炻怬㚱仢᷷⾓忇⍰⎗月 侭幓ᶲ炻忁㗗⚈䁢NOAC䘬埨ᷕ㽫⹎⋲堘㛇炻 䘬NOAC㩊㷔㕡㱽)炻⇯ᶵ⺢嬘IVTˤ 侴⋲堘㛇⛐僶≇傥ᶵἛ䘬か侭ˣ侩⸜Ṣˣ␴ ℞Ṿね㱩䓂军㚜䁢⺞攟2ˤ2018伶⚳AHA/ASA ĴįĴįijġġଢ଼૕ϱՖ੃ಋଶĩŦůťŰŷŢŴŤŶŭŢųġ guidelines⺢嬘炻ἧ䓐NOAC䘬か侭ᶵㅱ㍍⍿ ŵũųŰŮţŦŤŵŰŮźġņŗŕĪ IVT炻昌朆か侭㕤忶⍣48⮷㗪ℏ᷎㛒㚵䓐NOAC ⿍⿏仢埨⿏ᷕ桐䘤ἄ6⮷㗪ℏ炻⛐䴻忶䮑 ᶼ㚱㬋ⷠ僶≇傥炻ㆾ㗗埨㵚㩊㞍栗䣢㬋ⷠ䘬䚠 怠ᶼ㰺㚱㚵䓐㈿ↅ埨∹䘬か侭炻劍㗗㚱ℏ柠≽ 斄ↅ埨㊯㧁 (⤪PT INR/aPTT/platelet count/ecarin 傰旣⠆ㆾ㗗ᷕ⣏儎≽傰役䪗旣⠆炻EVT⶚塓嫱 clotting time/thrombin time/ factor Xa activity ⮎㗗㚱㓰43ˤℑᾳ⣂ᷕ⽫晐㨇⮵䄏娎槿嫱⮎炻 䫱)17ˤ ⿍⿏仢埨⿏ᷕ桐䘤ἄ⼴6-16冯6-24⮷㗪ℏ炻怠 䃞侴ἧ䓐ⷠ夷䘬PTㆾaPTTἮ姽ỘNOAC 㑯䈡⭂冐⸲㡅ẞ⍲儎悐⼙⁷㡅ẞ䘬⇵⽒䑘ᷕ桐 䘬喍㓰炻‥昘⿏䘬㨇㚫朆ⷠ檀炻⎒㚱thrombin か侭炻EVTṵ㚱≑㕤か侭䘬䤆䴻≇傥《⽑44, 45ˤ time (TT)⮵dabigatran⼰㓷デ炻⌛ἧ⼰Ỷ㽫⹎䘬 䚖⇵㫸㳚儎ᷕ桐䳬䷼(European Stroke dabigatranḇ㚫ἧTT⺞攟炻㇨ẍ㬋ⷠ䘬TT⎗ẍ Organization)⺢嬘炻⮵㕤䃉㱽忚埴IVT䘬か侭炻 ㌺昌dabigatran䘬喍㓰⬀⛐2炻ỮTT㩊㞍⣏⣂䃉 EVT㗗椾怠䘬㱣䗪㕡⺷炻侴伶⚳AHA䚖⇵⮵㕤 㱽彭忇⼿⇘䳸㝄ˤ 忁栆か侭㰺㚱䈡⇍䘬⺢嬘17, 46ˤ晾䃞忁ṃEVT䘬

149 ϛॳႱ٩ݽᕛࡾЕޱᡊᆰᠬଢ଼௉ܘᏗՖᏘҢܻЖתᏘο݈תŌࡼڼߨᆰт

䞼䨞炻㚱ṃ㗗㌺昌㚵䓐㈿ↅ埨∹䘬か侭炻㚱ṃ NOACỮ⍰ℵ㫉ᷕ桐㗪天㎃ㆸ⇍䧖NOACˤ怑 ⎒⊭⏓⮹㔠㚵䓐㈿ↅ埨∹䘬か侭炻Ữ㗗忁⮹㔠 䔞䘬NOAC∹慷ẍ⍲か侭㛔幓䘬㡅ẞ悥暨天塓 䘬䞼䨞䳸㝄㊯↢炻㚵䓐㈿ↅ埨∹䘬か侭炻㕥埴 Ṽ䳘姽Ộ4, 48, 49ˤ斄㕤AFか侭⛐TIAㆾ㗗⿍⿏仢 EVTḇ⎗傥㗗⬱ℐ䘬ˤ⛐ᶨ䭯大䎕䈁䘬⇵䝣⿏ 埨⿏ᷕ桐⼴炻ỽ㗪天≈⚆NOAC䘬⣏夷㧉䞼䨞 奨⮇䞼䨞栗䣢炻劍か侭ἧ䓐㈿ↅ埨∹㗪㍍⍿Ḯ 㔠㒂㗗仢᷷䘬ˤ EVT炻␴䃉ἧ䓐㈿ↅ埨∹䘬か侭䚠㭼炻䕯䉨⿏ ⚈㬌炻䚖⇵䘬⺢嬘㗗㟡㒂⮰⭞ℙ嬀シ夳炻 儎↢埨(16.7%㭼8.3%炻p = 0.13)ㆾᶱᾳ㚰㬣ṉ䌯 侴ᶼ≈⚆NOAC䘬冐⸲䉨㱩ㅱ娚冯warfarin栆 (6.7%㭼19%炻p = 0.08)䘮䃉栗叿ⶖ䔘47ˤ⚈㬌炻 Ụˤ⛐⿍⿏仢埨⿏ᷕ桐⼴≈⚆NOAC炻⽭枰天 劍か侭⚈ἧ䓐㈿ↅ埨∹侴ᶵ怑⎰㍍⍿IVT炻⎗ 堉慷ℵ㫉ᷕ桐冯㠿⠆⼴↢埨䘬桐晒5, 33ˤ⺢嬘⤪ 侫ㄖ忚埴EVTˤ2018 EHRA guidelines2 ㍸↢ἧ ⎴⇵朊㍸⇘䘬2018 EHRA guidelines2炻㟡㒂ᷕ 䓐NOAC䘬AFか侭䘤䓇⿍⿏仢埨⿏ᷕ桐ᷳ嗽伖 桐䦳⹎⍲℞Ṿ䚠斄桐晒Ἦ㰢⭂≈⚆NOAC䘬㗪 㳩䦳堐⤪⚾2ˤ 攻ˤ ⺢嬘烉 ĴįĵġીՖܒϛॳࡨܒࡣ෈ޟ೎ည (1) AFか侭䘤䓇⿍⿏仢埨⿏ᷕ桐㗪炻ᶵ⺢嬘㕤 䚖⇵᷎㰺㚱晐㨇⮵䄏䘬䞼䨞嫱㒂栗䣢㝸 ᷕ桐㖑㛇(⮷㕤48⮷㗪)ⷠ夷ἧ䓐偅䳈⍲Ỷ 䧖NOAC⃒㕤⎎ᶨ䧖NOAC炻ㆾ㗗䔞か侭㚵䓐 ↮⫸慷偅䳈 (Class III No Benefit, Level of

*䚖⇵⎘䀋⎒㚱dabigatran㚱⍵廱∹ (idarucizumab) #䔞㰺㚱℞Ṿ䤩⽴䕯䘬ね㱩ᶳㇵἧ䓐埨㞻㹞妋∹ %䔞㚱䈡⭂埨䭉旣⠆ᶼ䫎⎰䈡⭂冐⸲㡅ẞ㗪炻⎗侫ㄖ≽傰ℏ埨㞻䦣昌 **㟡㒂⮰⭞ℙ嬀

⚾2ˢ2018⸜㫸㳚⽫⼳⬠㚫㊯⺽ἧ䓐NOAC䘬AF䕭Ṣ䘤䓇⿍⿏仢埨⿏ᷕ桐ᷳ嗽伖㳩䦳⚾

150 ϛॳႱ٩ݽᕛࡾЕޱᡊᆰᠬଢ଼௉ܘᏗՖᏘҢܻЖתᏘο݈תŌࡼڼߨᆰт

Evidence A)ˤ ᷳ䵲⿍嗽伖⍲⼴临㱣䗪ὧ䚠䔞慵天ˤẍᶳ㇨媪 (2) ⮵㕤⣏悐↮⿍⿏仢埨⿏ᷕ桐䘬 AFか侭炻㕤 儎ℏ↢埨炻ᶵ⊭⏓㠿⠆⼴↢埨炻AF䘬か侭䘤䓇 䕯䉨䘤䓇⼴14⣑ℏ攳⥳ἧ䓐⎋㚵㈿ↅ埨∹㗗 㠿⠆⼴↢埨炻晾䃞䚖⇵⯂䃉冐⸲娎槿㍸ὃ㚨Ἓ ⎰䎮䘬(Class IIa, Level of Evidence B-NR)ˤ 䘬㈿ↅ埨∹ἧ䓐⍇⇯炻Ữ⣂⺢嬘⃰ẍ儎㠿⠆䘬 (3) AFか侭䘤䓇⿍⿏仢埨⿏ᷕ桐㗪炻IVTἧ䓐⍇ ♜慵⹎㰢⭂ἧ䓐㈿ↅ埨∹䘬㗪㨇炻ℵ⎎夾儎↢ ⇯烉 埨䘬♜慵⹎䴎Ḱ怑⹎⺞怚2ˤ A. 㚵䓐 warfarin䘬か侭炻䕯䉨䘤ἄ3⮷㗪 ᏗՖᏘᏲमᝒ१юՖϞתҢٺℏ炻劍INR ≤ 1.7炻⎗侫ㄖIVT (Class IIb, ĵįIJġġ Level of Evidence B-NR)ˤ ॳᓎ B. か侭劍⛐ᷕ桐䘤䓇⇵ 48⮷㗪ℏ㚦㚵䓐 ἧ䓐warfarin⍲NOAC䘤䓇♜慵↢埨∗ἄ䓐 NOAC (dabigatran, rivaroxaban, apixaban, 䘬桐晒↮⇍䲬䁢㭷⸜3.1-3.4%␴1.6-3.6%50-53炻 edoxaban)炻⇯ᶵ⺢嬘IVT (Class III, Level 侴栙ℏ↢埨䁢℞ᷕ㚨♜慵䘬Ἕ䘤䕯(46-74%䁢儎 of Evidence C-EO)炻侴㬌栆か侭劍㆟䔹 ℏ↢埨)炻℞䘤䓇䘬桐晒↮⇍䁢㭷⸜0.7-0.85% 㚱䈡⭂⣏埨䭉旣⠆㗪炻⎗侫ㄖ忚埴EVT ␴0.23-0.5%炻䘤䓇栙ℏ↢埨⼴ᶨᾳ㚰ℏ䘬㬣ṉ 54-57 (Class IIb, Level of Evidence B-NR)ˤ军 䌯↮⇍䁢35-50%␴38-48% (堐4)炻シ␛叿晾 㕤㚵䓐dabigatran䘬か侭炻⎗侫ㄖἧ䓐⍵ 䃞NOAC㭼warfarin䘬ἧ䓐㚱庫Ỷ䘬栙ℏ↢埨 廱∹idarucizumab⼴ℵ㕥埴IVT (Class IIb, 䘤䓇䌯炻Ữᶨ㖎䘤䓇栙ℏ↢埨炻ℑ侭䘬枸⼴䘮 Level of Evidence C-EO)ˤ ᶵ䎮゛ˤ⎘䀋╖ᶨᷕ⽫䞼䨞Ṏ栗䣢炻⎋㚵㈿ↅ 埨∹䚠斄䘬冒䘤⿏儎ℏ↢埨ᷳ㬣ṉ䌯␴枸⼴⛐ ᏗՖᏘᏲम warfarin⍲NOACℑ䳬㗗栆Ụ䘬58ˤ䃞侴劍傥㕤תҢٺޱĵįġġłŇ௉ ᝒ१юՖޟॳᓎЅ೎ည 㚵䓐⎋㚵㈿ↅ∹侴䘤䓇栙ℏ↢埨䘬か侭䵲⿍ἧ 䓐怑䔞䘬㈿ↅ埨∹ᷳ⍵廱∹炻℞㬣ṉ䌯⎗⣏ⷭ AF䘬か侭⣂暨攟㛇ἧ䓐⎋㚵㈿ↅ埨∹ẍ 䓙35-48%ᶳ旵军14-19%57, 59, 60 (堐4)ˤ 枸旚㛒Ἦ仢埨⿏ᷕ桐䘬䘤䓇炻晾䃞warfarin␴ ἧ䓐⎋㚵㈿ↅ埨∹侴䘤䓇栙ℏ↢埨䘬⌙ NOAC䘮㚱䘤䓇♜慵↢埨ḳẞ䓂军栙ℏ↢埨䘬 晒⚈⫸⊭㊔⸜䲨ˣ檀埨⡻ˣᷕ桐䕭⎚ˣ偅僶≇ 桐晒炻Ữ䓙㕤ἧ䓐⎋㚵㈿ↅ埨∹⮵か侭䘬㔜橼 傥ᶵ列ˣ↢埨䕭⎚ˣ⎰Ἕら⿏儓䗌ˣ惿惺ˣ ⤥嗽㖶栗⣏㕤⢆嗽炻⚈㬌䫎⎰怑ㅱ䕯䘬AFか侭 ㈿ↅ埨∹䘬喍䈑∹慷ˣ儎⮎岒ℏ䘬⽖⮷↢埨 䘮ㅱ侫ㄖ攟㛇ἧ䓐ˤỮ劍䘤䓇♜慵↢埨⿏Ἕ䘤 (microbleeds)ˣ儎䘥岒䕭嬲ˣ栆㽙䰱⿏儎埨䭉 䕯㗪炻㬋⛐ἧ䓐㈿ↅ埨∹䘬か侭炻㚫ἧ↢埨㚜 䕭嬲 (amyloid angiopathy)ˣ⎰Ἕ㈿埨⮷㜧喍䈑 ≈暋ẍ㍏⇞炻⚈㬌䔞㬌栆か侭䘤䓇♜慵↢埨㗪 ἧ䓐(⤪aspirin)䫱5, 54, 55ˤHAS-BLED score䁢姽

堐4ˢ⎋㚵㈿ↅ埨∹ᷳ↢埨䌯⍲栙ℏ↢埨㬣ṉ䌯

Warfarin Dabigatran Rivaroxaban Apixaban Edoxaban (150/110 mg) (60/30 mg) ♜慵↢埨(%/⸜) 3.1-3.4 3.1/2.7 3.6 2.1 3.8/1.6 栙ℏ↢埨(%/⸜) 0.7-0.85 0.3/0.23 0.5 0.33 0.39/0.26 栙ℏ↢埨ᶨᾳ㚰 35 vs. 19 38 vs. 16 48 (rivaroxaban), 㬣ṉ䌯(%) (FFP vs. PCC) *(䃉vs.ἧ䓐 45 (apixaban) vs. 14* idarucizumab) (䃉vs.ἧ䓐andexanet alpha) * 朆㕤冐⸲娎槿ᷕ䚜㍍㭼庫ˤFFP, fresh frozen plasma; PCC, prothrombin complex concentrate.

151 ϛॳႱ٩ݽᕛࡾЕޱᡊᆰᠬଢ଼௉ܘᏗՖᏘҢܻЖתᏘο݈תŌࡼڼߨᆰт

Ộἧ䓐⎋㚵㈿ↅ埨∹ᷳ↢埨桐晒䘬㊯㧁61炻㗗 ⎰Ἕἧ䓐℞⬫䚠斄喍䈑(⤪㈿埨⮷㜧喍䈑䫱)ˣ 䚖⇵㫸㳚⽫⼳⬠㚫⍲伶⚳⽫冇⬠㚫庫⺢嬘ἧ ⎗傥䘬↢埨⍇⚈(⤪⢾ 䫱)⍲㗗⏎㚱僶≇傥ᶵ 䓐䘬⍫侫㊯㧁2, 62炻↮㔠䁢0-9↮(堐5)炻HAS- 列䘬䕭⎚ˤ幓橼㩊㞍昌Ḯ䓇␥⽝尉⍲シ嬀≇ BLED score劍 ≥ 3↮⇯Ⱄ㕤檀↢埨桐晒䘬か侭炻 傥炻ㅱ夾↢埨䘬悐ỵ忚埴ᶵ⎴䘬姽Ộˤ㉥埨㩊 冐⸲ᶲ⎗傥暨庫⮷⽫⛘䚋㍏↢埨䘬䘤䓇炻侴㈿ 槿⊭㊔ẍᶳ枭䚖烉PT/aPTT/INRˣCBC/DCˣ 埨㞻喍䈑䘬䧖栆␴∹慷䘬怠㑯Ṏ⎗Ḱẍ⍫侫ˤ troponinˣ偅僶≇傥⍲暣妋岒㩊槿䫱ˤ⤪㝄㗗ἧ 䓐warfarin䘬か侭炻⇯ẍPT/INRḮ妋喍䈑䘬㽫 ᏗՖᏘᏲमᝒ१юՖϞ ⹎䉨㱩烊侴ἧ䓐dabigatran䘬か侭炻㩊㷔aPTT⍲תҢٺĵįijġġ ᆧࡨ೎ည TT㗗䚖⇵庫⭡㖻ἧ䓐䘬⭂⿏㕡㱽ˤ ἧ䓐⎋㚵㈿ↅ埨∹劍䘤䓇↢埨Ἕ䘤䕯炻䵲 ⮵㕤庽⹎↢埨Ἕ䘤䕯(⤪堐䙖⢾ ㆾ䈁漎 ⿍嗽伖䘬⍇⇯ᷣ天⍾㰢㕤↢埨䘬♜慵⹎炻᷎侫 ↢埨䫱)炻昌Ḯ⎗忚埴⯨悐㊱⡻㬊埨炻⎗⛐姽Ộ 慷⎋㚵㈿ↅ埨∹䘬䧖栆⍲∹慷ˣ㚨役ᶨ㫉㚵䓐 ↢埨⍲埨㞻桐晒⼴炻⺞⼴ㆾ㙓 ᶳᶨᾳ㈿ↅ埨 喍䈑䘬㗪攻ˣ僶≇傥䉨ンˣ㉥埨㩊槿䳸㝄(⤪ ∹ᷳ∹慷ˤ憅⮵ᶵ⎴↢埨䘬ỵ伖炻⎗忚埴䚠斄 INRˣPTT⍲hemoglobin䫱)ˣ⍲か侭ℵ䘤䓇埨 䘬㱣䗪⍲⼴临㩊㞍炻⤪偫↢埨炻⎗䴎Ḱproton 㞻ḳẞ䘬桐晒䫱ˤ劍䘤䓇⌙⿍䓇␥䘬♜慵↢埨 pump inhibitor (PPI)炻᷎夾ね⼊侫ㄖ㗗⏎⬱㌺ℏ (⤪栙ℏ↢埨)炻昌ᶨ凔䵲⿍嗽伖⢾炻⣂暨ἧ䓐 夾掉㩊㞍ˤ劍か侭慵央䘤䓇↢埨炻㚧㎃ᶵ⎴䧖 ⎋㚵㈿ↅ埨∹䘬⍵廱∹(堐6)2, 5, 63ˤ䃞侴ẍᶲ嗽 栆䘬⎋㚵㈿ↅ埨∹㗗⎰䎮䘬2, 5炻ᶼ暨㲐シ㗗⏎ 伖暨⸛堉か侭⍇伡かᷳAF䘤䓇⼴临埨㞻ḳẞ䘬 㚱儠偫忻儓䗌䘬⎗傥⿏ (䲬⌈儠偫忻↢埨か侭 桐晒炻忚埴㔜橼侫慷ẍἄ↢㰢䫾炻᷎␴か侭⍲ 䘬8%)64ˤ ⭞Ⱄ婒㖶␴妶婾ˤ ⮵㕤ᷕ⹎↢埨侭炻℞嗽伖昌ẍᶲ⍇⇯⢾炻 怬⊭㊔㬊埨(↢埨溆⡻従ˣℏ夾掉㬊埨ˣㇳ埻 ĵįijįIJġΙૡᆧࡨຟեЅ೎ညġ 㬊埨䫱)ˣ廠㵚㓗㊩(廠㵚ˣ廠埨䫱)⍲旵Ỷ㈿ↅ ᶨ㖎䘤䓇⎋㚵㈿ↅ埨∹ᷳ↢埨Ἕ䘤䕯炻 埨∹⼙枧ᷳ䚠斄㱣䗪ˤ劍㚱暨天炻廠埨⎗⊭㊔ 昌Ḯ慸㶭↢埨䘬♜慵⹎炻ㅱ⾓忇Ḯ妋䚠斄䕭 䲭埨䎫㽫⍂㵚(packed RBC)ˣ埨⮷㜧(劍埨㵚 ⎚炻⤪㇨ἧ䓐喍䈑䘬䧖栆⍲∹慷ˣ㗪攻ˣ㗗⏎ 埨⮷㜧㽫⹎< 60000/uLㆾ㚱埨⮷㜧≇傥䔘ⷠ)ㆾ

堐5ˢHAS-BLED score姽↮堐

↢埨⌙晒⚈⫸ ↮㔠 Hypertension: 㛒㍏⇞䘬檀埨⡻炻SBP > 160 mmHgˤ 1 Abnormal renal and liver function (1 point each): 1 or 2 僶≇傥䔘ⷠ⊭㊔ㄊ⿏㲿僶ˣ僶冇䦣㢵ㆾ倴惸愠>200 mmol/L (䲬2.26 mg/dL)烊偅≇傥䔘ⷠ ⊭㊔ㄊ⿏偅冇䕦䕭ㆾ湫䕠檀㕤㬋ⷠῤ2᾵ẍᶲㆾ偅㊯㔠檀㕤㬋ⷠῤ3᾵ᶲˤ Stroke: 忶⍣㚱ᷕ桐䕭⎚炻⯌℞㲐シ⮷攻晁㠿⠆ˤ 1 Bleeding history or predisposition: 忶⍣㚱↢埨䘬䕭⎚ㆾ℟↢埨⁦⎹ˤ 1 Labile INRs: ᶵ䨑⭂䘬INR (ἧ䓐 warfarin 㗪)炻TTR < 60%ˤ 1 Elderly: ⸜漉 > 65㬚ˤ 1 Drugs or alcohol (1 point each) 1 or 2 ⎴㗪⎰Ἕἧ䓐⎗傥⭡㖻⮶农↢埨䘬喍䈑 (⤪㈿埨⮷㜧ㆾ朆栆⚢愯㴰䀶喍䈑䫱)ㆾ忶慷梚惺ˤ INR, international normalized ratio; TTR, time in therapeutic range.

152 ϛॳႱ٩ݽᕛࡾЕޱᡊᆰᠬଢ଼௉ܘᏗՖᏘҢܻЖתᏘο݈תŌࡼڼߨᆰт

堐6ˢ⎋㚵㈿ↅ埨∹䚠斄↢埨Ἕ䘤䕯ᷳ䵲⿍冐⸲嗽伖

↢埨Ἕ䘤䘬♜慵⹎ 䵲⿍冐⸲嗽伖

庽⹎ ⯨悐㊱⡻㬊埨 ⺞⼴ᶳᶨᾳ㈿ↅ埨∹ᷳ∹慷ㆾ㙓㗪 䓐 侫慷⼴临ἧ䓐㈿ↅ埨∹ᷳ䧖栆␴∹慷⍲暨Ἕ䓐䘬℞⬫喍䈑

ᷕ⹎ 昌ẍᶲ䵲⿍嗽伖炻⎎侫ㄖ烉 廠㵚⍲廠埨 (夾ね㱩䴎Ḱ䲭埨䎫㽫䷖㵚ˣ埨⮷㜧ㆾFFP) 㕤2⮷㗪ℏ㚦㚵䓐NOAC㗪⎗侫ㄖἧ䓐⎋㚵㳣⿏䡛50⃳㲿偫 䵕㊩嵛⣈䘬⯧慷 ᷳ⇵ἧ䓐warfarin侭炻⎗侫ㄖ㲐⮬vitamin K (1-10 mg, IV) ᷳ⇵ἧ䓐dabigatran侭炻⎗侫ㄖ㲐⮬idarucizumab (5 g, IV)ㆾ忚埴㲿僶 Tranexamic acid⎗侫ㄖἄ䁢庼≑㱣䗪(1 g, IV, 夾ね㱩⎗㭷6⮷㗪ἧ䓐) ㇳ埻㬊埨ㆾℏ夾掉㬊埨

慵⹎ 昌ẍᶲ䵲⿍嗽伖炻⎎⎗ἧ䓐䚠斄㈿ↅ埨∹ᷳ⍵廱∹ warfarin烉侫ㄖ㲐⮬vitamin K (10 mg, IV) + PCC (25-50U/kg, IV) dabigatran烉侫ㄖ㲐⮬idarucizumab (5g, IV) rivaroxaban, apixaban, edoxaban烉侫ㄖ㲐⮬PCC (25-50U/kg, IV) * FFP: fresh frozen plasma; PCC: prothrombin complex concentrate; IV: intravenous. *㛒Ἦ劍㚱andexanet-α⎗ὃἧ䓐㗪⇯⎗侫ㄖ䴻朄傰䴎Ḱandexanet-αˤ

FFPˤ劍か侭㚵䓐㈿ↅ埨喍䈑⯂㕤2⮷㗪ℏ炻⎗ ἧ䓐䴻朄傰vitamin K㲐⮬㱣䗪(10 mg)⎗ 侫ㄖἧ䓐⎋㚵㳣⿏䡛50⃳㲿偫ˤ侴ᾅ㊩嵛⣈䘬 ⍵廱warfarin䘬㓰㝄炻㲐⮬ㅱ崭忶20-30↮揀ẍ ⯧㵚慷⎗⸓≑喍䈑䘬ẋ嫅ˤ㕤ἧ䓐warfarin䘬 㷃⮹忶㓷䘬桐晒炻侴䴻⎋ㆾ䴻䙖ᶳ/倴倱㲐⮬ か侭炻⎗侫ㄖ䴻朄傰㲐⮬vitamin K (1-10 mg)烊 ↮⇍„㚱㚵䓐⚘暋⍲⏠㓞ᶵ䨑⭂䘬⓷柴侴庫ᶵ 侴㕤ἧ䓐dabigatran䘬か侭炻⎗侫ㄖ䴻朄傰㲐⮬ ⺢嬘ˤỮ⌛ἧ⤪㬌炻vitamin K暨天6-12⮷㗪ㇵ idarucizumab (5 g)ㆾ忚埴㲿僶ẍ旵Ỷdabigatran 傥䞗㬋INR炻⚈㬌⎎暨⎰Ἕↅ埨⚈⫸墥∹䘬㱣 喍䈑㽫⹎ˤ㬌⢾炻晾䃞䚖⇵䞼䨞嫱㒂㚱旸炻ẍ 䗪ˤFFP䁢忶⍣ⷠ䓐䘬墥∹炻℞仢溆㗗暨⣏慷 㲐⮬tranexamic acidἄ䁢庼≑㱣䗪㗗⎰䎮䘬怠㑯 廠㵚㿴㲐⍲㱣䗪便㗪ˤᶼ役⸜Ἦ䞼䨞䘤䎦炻 (1 g炻夾ね㱩⎗㭷6⮷㗪ἧ䓐)2ˤ 4-factor PCC (⏓䫔2ˣ7ˣ9ˣ10⚈⫸)庫FFP䘬䗪 㓰Ἓ烉㕤50ỵwarfarin䚠斄ᷳ栙ℏ↢埨か侭䘬 ᏗՖᏘϞІᙽᏘ ↮㜸䳸㝄䘤䎦炻vitamin K⎰Ἕ4-factor PCC㱣䗪תҢٺĵįijįijġ 憅⮵慵⹎䓂军⌙⍲䓇␥ᷳ↢埨炻昌ẍ ␴vitamin K⎰ἝFFP㱣䗪䚠㭼炻4-factor PCC傥 ᶲ嗽伖⢾炻⣂暨ἧ䓐䚠⮵ㅱ䘬⍵廱∹ˤἧ䓐 ⾓忇䞗㬋INR (3⮷㗪炻64%㭼9%炻p = 0.0003)⍲ warfarin䘬か侭炻侫ㄖ䴻朄傰㲐⮬vitamin K 㷃⮹栙ℏ↢埨慷䘬⡆≈(8㭼22 ml炻p = 0.018)庫 ⎰ἝPCC烊ἧ䓐dabigatran䘬か侭炻侫ㄖ䴻朄 FFP栗叿57ˤ⎎㕤202ỵwarfarin䚠斄ᷳ♜慵↢埨 傰㲐⮬idarucizumab烊ἧ䓐䫔⋩⚈⫸㈹⇞∹ か侭↮㜸栗䣢炻4-factor PCC䚠⮵庫plasma傥⾓ (rivaroxaban, apixaban, edoxaban)䘬か侭炻⛐℞ 忇䞗㬋INR (30↮揀炻62%㭼10%)炻Ữℑ䳬忼⇘ ⮰ᶨ⍵廱∹andexanet-α䞕㛇ℏ怬⯂㛒傥ἧ䓐䘬 㬊埨䚖㧁䘬㭼䌯(72%㭼65%)䚠Ụ65ˤ⚈㬌炻ἧ ね㱩ᶳ炻⎗侫ㄖ䴻朄傰㲐⮬PCCˤ 䓐warfarinか侭䔞䘤䓇⌙⿍䓇␥ᷳ♜慵↢埨炻ㅱ ẍ⎰Ἕἧ䓐朄傰廠㲐vitamin K (10 mg)⍲4-factor ŘŢųŧŢųŪůІᙽᏘ PCC (⤪BeriplexˣFeiba炻25-50 U/kg)䁢椾怠炻

153 ϛॳႱ٩ݽᕛࡾЕޱᡊᆰᠬଢ଼௉ܘᏗՖᏘҢܻЖתᏘο݈תŌࡼڼߨᆰт

⎘䀋䚖⇵‍ᾅ会憅⮵㬌怑ㅱ䕯⶚㚱䴎Ẁ炻Ữἧ ↮㜸炻℞䳸㝄栗䣢60炻ἧ䓐andexanet-α⎗旵Ỷ 䓐ᶲṵ暨㲐シ䘤䓇㞻⠆ḳẞ䘬⎗傥⿏ˤ侴╖䲼 䫔⋩⚈⫸㳣⿏忼92% (rivaroxabanㆾapixaban)炻 䫔ᶫ⚈⫸墥∹(NovoSeven)⚈䗪㓰㚱旸66炻ᶼṎ ᶼ85%儠偫忻↢埨⍲80%栙ℏ↢埨䘬か侭㕤 ⎗傥䘤䓇㞻⠆ḳẞ炻䚖⇵ᶵ⺢嬘ⷠ夷ἧ䓐ˤ andexanet-αἧ䓐12⮷㗪⼴⎗忼⇘列⤥䘬㬊埨䉨 ンˤ㕤ἧ䓐rivaroxaban (嶅㚨役㚵喍㗪攻崭忶7 ŅŢţŪŨŢŵųŢůІᙽᏘ ⮷㗪ẍᶲ)⍲apixaban䘬か侭炻andexanet-α䘬∹ Idarucizumab㗗dabigatran䘬⮰ᶨ⍵廱∹炻 慷䁢400 mg⾓忇廠㲐(15-30↮揀)炻ℵ㕤2⮷㗪ᷕ ℞䁢Ṣ栆⊾㈿橼(humanized antibody)䘬䇯㭝炻 䶑ㄊ㺜㲐480 mg (4 mg/min)烊㕤ἧ䓐rivaroxaban 傥䱦㸾䳸⎰dabigatran侴ἧ℞⣙⍣ἄ䓐ˤ㕤⣏✳ (嶅㚨役㚵喍㗪攻⮷㕤7⮷㗪ㆾ㗪攻ᶵ㖶侭)⍲ 冐⸲娎槿REVERSE-ADᷳ503ỵか侭䘤䎦54炻 edoxaban䘬か侭炻℞∹慷䁢800 mg⾓忇廠㲐 䃉婾㗗㚵䓐dabigatran⼴䘤䓇⌙⿍⿏↢埨(301 (15-30↮揀)炻ℵ㕤2⮷㗪ᷕ䶑ㄊ㺜㲐960 mgˤ Ṣ)ㆾ暨䵲⿍ㇳ埻(202Ṣ)䘬䉨㱩炻idarucizumab 枰㲐シ䘬㗗andexanet-α䘬⍵廱㓰㝄㕤 㬊㺜㲐 䘬ἧ䓐⎗⾓忇ˣ㚱㓰ᶼ㊩临(12-24⮷㗪)⛘⍵廱 ⼴4⮷㗪ᷳ㗪炻∑傥旵Ỷ䫔⋩⚈⫸㳣⿏忼42% dabigatran䘬㈿ↅ㓰㝄ˤか侭⛐15↮揀ℏ㍍⍿ℑ (rivaroxaban)⍲32% (apixaban)69炻ẋ堐℞㓰㝄䃉 ∹⎬2.5 g䘬idarucizumab䴻朄傰㲐⮬⼴炻↮㜸 㱽㊩临ˤ 䳸㝄栗䣢㕤㲐⮬⚃⮷㗪ℏ⬴ℐ䞗㬋dabigatran㓰 䚖⇵andexanet-α⶚忂忶伶⚳FDAἧ䓐㕤䫔 㝄䘬ᷕỵ㔠㭼䌯䁢100%ˤ娎槿か侭ᷕ㚱98Ṣ ⋩⚈⫸㈹⇞∹䚠斄䘬♜慵↢埨Ἕ䘤䕯炻Ữ⎘䀋 䁢栙ℏ↢埨か侭炻℞30⣑㬣ṉ䌯䁢16.4%54炻⮵ ⍲㫸䚇䘮⯂㛒㟠Ⅾˤ⛐andexanet-αṵ䃉㱽ἧ䓐 㭼ᷳ⇵dabigatran冐⸲娎槿(㛒ἧ䓐idarucizumab) 䘬ね⼊ᶳ炻侫ㄖẍPCCἄ䁢㚧ẋ䘬⍵廱∹㗗⎰ 䘬栙ℏ↢埨か侭㬣ṉ䌯37.5%50炻idarucizumab 䎮䘬怠㑯炻Ữ䚖⇵⎘䀋‍ᾅ会⯂䃉䴎Ẁ㕤㬌栆 䘬ἧ䓐Ụ㚱旵Ỷ↢埨㬣ṉ䌯䘬㭼ἳˤ⼴临䘤 か侭ˤ㕤NOACἧ䓐ᶳ䘤䓇♜慵↢埨㗪炻PCC 堐䘬⽟⚳12ἳ栙ℏ↢埨ᷳ㟰ἳ↮㜸䘤䎦炻ἧ䓐 䘬䗪㓰⯂䃉⣏✳冐⸲娎槿䳸㝄嫱⮎炻侴役㛇ℑ idarucizumab⼴䘬㬣ṉ䌯䁢8.3%37ˤ侴㕤⎘䀋䘬5 奨⮇⿏䞼䨞栗䣢炻㕤281ỵ⍲84ỵἧ䓐NOACᶼ ἳ栙ℏ↢埨᷎㍍⍿idarucizumab㱣䗪ᷳ㟰ἳṎ栗 䘤䓇♜慵↢埨ᷳか侭炻PCC (䲬25-50 U/Kg)䘬ἧ 䣢炻㇨㚱か侭䘮䃉⼴临↢埨㒜⣏䘬ね⼊67ˤ⚈㬌 䓐↮⇍㚱81%⍲69%䘬か侭⎗忼⬴ℐㆾ悐↮㬊 㕤㍍⍿dabigatran侴䘤䓇♜慵↢埨䘬か侭炻䚉⾓ 埨䘬㓰㝄70, 71ˤᶨᾳ䫔ᶨ㛇冐⸲娎槿嫱⮎炻PCC 䴻朄傰㲐⮬idarucizumab 5 g䁢䚖⇵椾怠䘬㱣䗪 (50 U/Kg)傥㚱㓰⍵廱edoxaban䘬㈿ↅ㓰㝄72ˤ䃞 㕡⺷ˤ⛐㕥ㇻidarucizumab侴㬊埨⼴炻慵㕘ἧ䓐 侴⎎ᶨ䞼䨞⚆㹗↮㜸146ỵἧ䓐NOAC䘤䓇儎ℏ dabigatranṵ傥忼⇘℞㈿ↅ㓰㝄烊侴劍⼴临暨ℵ ↢埨䘬か侭炻䘤䎦PCC䘬ἧ䓐冯㗗⏎䘤䓇儎↢ 㫉ἧ䓐idarucizumab炻ṵ傥ᾅ㊩℞⍵廱䗪㓰68ˤ 埨㒜⣏ˣ㬣ṉ䌯⍲枸⼴䘮䃉栗叿䚠斄73炻⚈㬌 NOAC⮰ᶨ䘬⍵廱∹ṵㅱ䁢㛒Ἦ䘬椾怠喍䈑ˤ œŪŷŢųŰŹŢţŢůĭġŢűŪŹŢţŢůĭġŦťŰŹŢţŢů ⎎ᶨ⍵廱∹ciraparantag傥德忶㯓挝␴㇨㚱ᶵ⎴ ІᙽᏘ 栆✳䘬NOAC䳸⎰炻忚侴⍵廱㈿ↅ∹䘬ἄ䓐炻 Andexanet-α䁢䓙䫔⋩⚈⫸䴻婧㔜≇傥 ℞⶚㕤䫔ᶨ㛇冐⸲娎槿嫱⮎╖ᶨ∹慷朄傰㲐⮬ ➢㇨⼿ᷳ埵䓇䈑炻℞⎗␴䫔⋩⚈⫸㈹⇞∹ ⎗⍵廱edoxaban䘬㈿ↅ埨ἄ䓐74炻䚖⇵㬌喍䈑怬 (rivaroxaban, apixaban, edoxaban䫱)䪞䇕䫔⋩⚈ ⛐忚埴⼴临冐⸲娎槿䞼䨞ˤ ⫸侴忼⇘⍵廱㓰㝄ᷳ⍵廱∹ˤANNEXA-4娎 ᏗՖᏘᏲमᝒ१תҢٺޱ槿憅⮵352ỵἧ䓐䫔⋩⚈⫸㈹⇞∹(rivaroxaban ĵįĴġġłŇ௉ 36%, apixaban 55%)侴䘤䓇♜慵↢埨ᷳか侭忚埴 юՖޟࡣ៉೎ည

154 ϛॳႱ٩ݽᕛࡾЕޱᡊᆰᠬଢ଼௉ܘᏗՖᏘҢܻЖתᏘο݈תŌࡼڼߨᆰт

ᶨ㖎か侭⚈♜慵↢埨侴 㬊ἧ䓐㈿ↅ埨∹ ⎴㗪㍍⍿㓗㝞㱣䗪)⍲↢埨䘬⍇⚈䃉㱽妋㰢䫱2, 䓂军㍍⍿⍵廱∹㱣䗪⼴炻AF忈ㆸ埨㞻ḳẞ䘬㨇 5ˤ劍㰢⭂ℵ㫉ἧ䓐⎋㚵㈿ↅ埨∹炻℞≈⚆䘬㗪 㚫⌛㚫⡆≈ˤ㕤REVERSED-AD⍲ANNEXA-4 攻溆䚖⇵⯂䃉⭂婾炻㫸㳚㊯⺽⺢嬘㕤栙ℏ↢埨 冐⸲娎槿ᷕ炻♜慵↢埨か侭㕤㍍⍿⮰ᶨ⍵廱∹ ⼴1-2ᾳ㚰ℵ≈⚆㈿ↅ埨∹2, 5ˤ侴⮵㕤䘤䓇♜慵 ⼴1ᾳ㚰ℏ炻↮⇍㚱4.6%⍲10%䘬か侭䘤䓇Ḯ㞻 儠偫忻↢埨䘬か侭炻劍暨ℵ㫉ἧ䓐⎋㚵㈿ↅ埨 ⠆ḳẞ炻侴⣂㔠か侭䘮⯂㛒攳⥳ἧ䓐㈿ↅ埨∹ ∹炻㫸㳚㊯⺽⺢嬘㕤4-7⣑⼴ἧ䓐2ˤ憅⮵䃉㱽 59, 60ˤ䃞侴か侭劍㚦⚈ᷳ⇵ἧ䓐㈿ↅ埨∹侴䘤䓇 攟㛇ἧ䓐⎋㚵㈿ↅ埨∹䘬AFか侭炻ẍ⽫⮶䭉忚 Ḯ♜慵↢埨(⯌℞㗗儎ℏ↢埨)炻㗗⏎㇨㚱か侭 埴ⶎ⽫㇧⽫俛(left atrial appendage, LAA)⮩攱ㇳ 䘮暨ℵ㫉ἧ䓐㈿ↅ埨∹炻䚖⇵ṵ㚱妶婾䨢攻ˤ 埻㗗⎰䎮䘬怠㑯炻䚖⇵⎘䀋‍ᾅ会⶚㚱䴎Ẁ炻 ᶨᾳ⊭⏓2,452ỵか侭䘬䴙⎰↮㜸栗䣢炻㕤䘤 晾䃞LAA⮩攱ㇳ埻⎗栗叿ᶳ旵ᶨ凔AFか侭䘤䓇 䓇栙ℏ↢埨䘬AFか侭炻⼴临ἧ䓐warfarin↮⇍ ᷕ桐⍲埨㞻ḳẞ䘬桐晒77炻Ữ㗗⏎㕤䘤䓇忶♜ ␴ἧ䓐㈿埨⮷㜧喍䈑⍲䃉ἧ䓐喍䈑䚠庫炻䘮⎗ 慵↢埨䘬か侭炻LAA⮩攱ㇳ埻⎗䓐ẍ⍾ẋ⎋㚵 ᶳ旵䘤䓇仢埨⿏ᷕ桐䘬㨇㚫(䚠⮵桐晒烉0.45⍲ ㈿ↅ埨∹炻ṵ暨⼴临䞼䨞嫱⮎ˤ 0.47炻p = 0.002⍲0.002)炻Ữ䃉栗叿⡆≈ℵ㫉䘤 ⺢嬘烉 䓇栙ℏ↢埨䘬桐晒 (䚠⮵桐晒烉1.34⍲0.93)75ˤ (1) ἧ䓐 warfarin䘬か侭劍䘤䓇⌙⿍䓇␥ᷳ♜ ⎎ᶨ⊭⏓1,012ỵか侭䘬䴙⎰↮㜸Ṏ栗䣢炻㕤䘤 慵↢埨炻ㅱ侫ㄖ⎰Ἕἧ䓐朄傰廠㲐vitamin 䓇儎ℏ↢埨䘬か侭炻䃉婾㗗儎叱ㆾ㶙悐↢埨炻 K (10 mg)⍲4-factor PCC (25-50 IU/kg)⍵ ⼴临ἧ䓐⎋㚵㈿ↅ埨∹䘮⎗栗叿㓡┬㬣ṉ䌯ˣ 廱warfarin䘬㈿ↅ埨㓰㝄(Class IIa, Level of 枸⼴⍲ℵᷕ桐(仢埨≈ᶲ↢埨⿏ᷕ桐)䘬桐晒(p Evidence A)ˤ < 0.005)炻ᶼᶵ⡆≈儎↢埨䘤䓇䘬㨇䌯76ˤ憅⮵ (2) ㍍⍿ dabigatran侴䘤䓇♜慵↢埨䘬か侭炻 㬌栆墯暄䘬冐⸲ね⠫炻䚖⇵⶚㚱⣂ᾳ⣏✳冐 ㅱ侫ㄖ䴻朄傰㲐⮬idarucizumab 5 g⍵廱 ⸲娎槿㬋⛐忚埴ᷕ(APACHE-AFˣSoSTARTˣ dabigatran䘬㈿ↅ埨㓰㝄(Class I, Level of NASPAF-ICHˣA3ICHˣSTATICHˣASPIREˣ Evidence B-NR)ˤ PRESTIGE-AF)ˤ (3) ㍍⍿䫔⋩⚈⫸㈹⇞∹ (rivaroxaban, apixaban 憅⮵ἧ䓐㈿ↅ埨∹䘤䓇♜慵↢埨䘬か侭炻 䫱)侴䘤䓇⌙⿍䓇␥ᷳ♜慵↢埨䘬か侭炻ㅱ ⛐䚠斄䞼䨞⯂㛒㚱䳸婾ᷳ⇵炻冐⸲㰢䫾ㅱṼ䳘 侫ㄖ䴻朄傰㲐⮬andexanet-α⍵廱℞㈿ↅ埨 侫慷㭷ỵ℟AFか侭炻ᷳ⇵♜慵↢埨䘬栆✳␴⍇ 㓰㝄(Class I, Level of Evidence B-NR)炻侴ẍ ⚈炻ẍ⍲㛒Ἦ䘤䓇埨㞻ḳẞ␴↢埨Ἕ䘤䕯桐晒 PCCἄ䁢㚧ẋ䘬⍵廱∹㗗⎰䎮䘬怠㑯(Class 䘬㨇㚫檀Ỷˤ⮵㕤栙ℏ↢埨䘬か侭炻怑⎰ℵ≈ IIb, Level of Evidence C-LD)ˤ ⚆㈿ↅ埨∹䘬ね⼊⊭㊔烉⢾ ✳↢埨ˣ➢⸽㟠 (4) 㕤䘤䓇栙ℏ↢埨䘬 AFか侭劍㰢⭂ἧ䓐⎋㚵 ↢埨ˣ⸜䲨庫庽ˣ囀嚃䵚兄ᶳ↢埨ᶼ≽傰䗌⶚ ㈿ↅ埨∹炻℞ἧ䓐䘬㗪攻溆䚖⇵⯂䃉⭂婾炻 䴻ㇳ埻ㆾ㞻⠆嗽伖ˣᷳ⇵ἧ䓐warfarinㆾ崭慷 ⛐堉慷冐⸲桐晒⼴⎗侫ㄖ㕤栙ℏ↢埨㔠忙 䘬㈿ↅ埨∹ˣ列⤥䘬埨⡻㍏⇞ˣ䃉ㆾ庽⽖䘬儎 ⼴(⤪4-8忙)≈ᶲ㈿ↅ埨∹(Class IIb, Level of 䘥岒䕭嬲⍲檀⹎仢埨⿏ᷕ桐䘬桐晒䫱ˤ侴䚠⮵ Evidence C-EO)ˤ ᶵ怑⎰ℵἧ䓐㈿ↅ埨∹䘬⚈䳈⊭㊔烉侩⸜Ṣˣ (5) 憅⮵䃉㱽攟㛇ἧ䓐⎋㚵㈿ↅ埨∹䘬か侭炻 儎叱↢埨(lobar hemorrhage)ˣ姢㕟䁢⣏儎栆㽙 ẍ⽫⮶䭉忚埴LAA⮩攱ㇳ埻㗗⎰䎮䘬怠㑯 䰱埨䭉䕭嬲ˣ⣂慷䘬儎ℏ⽖⮷↢埨㔠䚖(≥ 5)ˣ (Class IIb, Level of Evidence B-NR)ˤ ⼴临埨⡻㍏⇞⚘暋ˣ⎎暨ἧ䓐㈿埨⮷㜧喍䈑(⤪

155 ϛॳႱ٩ݽᕛࡾЕޱᡊᆰᠬଢ଼௉ܘᏗՖᏘҢܻЖתᏘο݈תŌࡼڼߨᆰт

೎ည 䓊⼴⒢ḛ㛇攻ἧ䓐ˤޟݷޑח੫ۡᖝޱĶįġłŇ௉ ⺢嬘烉 (1) ⎰Ἕ㚱 AF䘬䓊⨎ㅱ塓夾䁢檀⌙晒⤲⧈炻⺢ ijĭġĴĭġĶ ѹஏ 嬘␴䤆䴻䥹ˣ⽫冇䥹ˣ䓊䥹冯⮷⃺䥹⮰䥹慓ޟݷȗłŇޑחᖝޟĶįIJġġ੫ۡ ⫽㛇⮵埨㵚䘬⼙枧忈ㆸ⭡㖻ↅ埨䘬䉨ン ⷓᶨ崟⎰ἄ䄏嬟㰢⭂㱣䗪㕡憅(Class I, Level (hypercoagulable state)炻⚈㬌␴㛒㆟⫽䘬AF⤛ of Evidence C-EO)ˤ ⿏䚠㭼炻㆟⫽䘬AF⤛⿏忈ㆸ仢埨⿏ᷕ桐ㆾ℞Ṿ (2) 暨天ἧ䓐㈿ↅ埨∹㱣䗪䘬⨎⤛⛐㆟⫽㛇攻⍲ 埨㞻ḳẞ䘬⌙晒⡆≈Ḯ3-4᾵78, 79ˤỮ䓙㕤㈿ↅ ⛐䓊⼴⒢ḛ㛇攻炻ᶵ⺢嬘ἧ䓐NOAC (Class 埨∹℟㚱⮵⫽⨎ẍ⍲偶⃺䘬㼃⛐⌙晒⿏炻⛐㆟ III, Level of Evidence C-LD)ˤ ⫽㛇攻⤪ỽἧ䓐㈿ↅ埨∹㗗ᶨᾳ℟㊹㇘⿏䘬嬘 (3) 暨天ἧ䓐㈿ↅ埨∹㱣䗪䘬䓊⨎⛐㆟⫽ 6-12 柴ˤ䓙㕤仢⮹䚠斄䘬冐⸲娎槿炻䚖⇵⮵㕤⎰Ἕ 忙ẍ⍲36忙⼴炻ᶵ⺢嬘ἧ䓐VKA (Class III, 㚱AF䘬⫽⨎ᷳᷕ桐枸旚炻᷎㰺㚱䈡⭂䘬㸾⇯ˤ Level of Evidence C-LD)ˤ ⎰Ἕ㚱AF䘬䓊⨎ㅱ塓夾䁢檀⌙晒⤲⧈炻⺢嬘␴ (4) 暨天ἧ䓐㈿ↅ埨∹㱣䗪䘬⨎⤛⛐㆟⫽㛇攻炻 䤆䴻䥹ˣ⽫冇䥹ˣ䓊䥹冯⮷⃺䥹⮰䥹慓ⷓᶨ崟 LMWH㗗㭼庫⬱ℐ䘬㈿ↅ埨∹怠㑯 (Class ⎰ἄ䄏嬟ˤ劍姽Ộ娵䁢㈿ↅ埨∹䘬攳䩳⇑⣏㕤 IIb, Level of Evidence C-LD)ˤ ⺲㗪炻ẍᶳ㗗㈿ↅ埨∹怠㑯䘬⺢嬘烉 (5) 暨天ἧ䓐㈿ↅ埨∹㱣䗪䘬⨎⤛⛐䓊⼴⒢ḛ㛇 ⛐⫽㛇⮵㕤㈿ↅ埨∹䧖栆䘬怠㑯ᷣ天侫慷 攻炻VKAẍ⍲LMWH㗗㭼庫⬱ℐ䘬㈿ↅ埨 䘬㗗喍䈑䨧德偶䚌䘬傥≃炻NOAC䘬AF冐⸲娎 ∹怠㑯(Class IIb, Level of Evidence C-LD)ˤ 槿䘮㌺昌Ḯ㆟⫽侭ˤᶼNOAC㑩㚱庫⮷䘬↮⫸ ܒඌځݷȗłŇӫޑחᖝޟ慷炻⣏滈⮎槿䘤䎦℞㑩㚱䨧德偶䚌䘬傥≃80炻 Ķįijġġ੫ۡ ⚈㬌⛐㆟⫽㛇攻ᶵ⺢嬘ἧ䓐NOACˤ ရዴ VKA⎗䨧德偶䚌᷎⎗傥忈ㆸ㳩䓊炻偶⃺↢ ら⿏儓䗌⎴㗪ⷞἮ埨㞻冯↢埨䘬檀桐晒ˤ 埨ẍ⍲䔠偶ˤ偶⃺䔠⼊忂ⷠ㗗⛐䫔ᶨ⫽㛇㗪ἧ 䚖⇵⶚䘤堐⮵㕤ら⿏儓䗌か侭䘬㈿ↅ埨∹冐⸲ 䓐VKA䓊䓇78炻⚈㬌忂ⷠ⺢嬘㆟⫽6-12忙㗪性 娎槿⣂㗗憅⮵朄傰㞻⠆䘬䘤䓇⍲枸旚2, 84-87炻侴 ⃵VKA䘬ἧ䓐炻⯌℞㗗VKA䘬∹慷⣏㕤5 mg/ ᶵ㗗憅⮵⎰ἝAF㗪䘬ᷕ桐枸旚ˤ⚈㬌䚖⇵⮵㕤 㖍81ˤ⎎⢾炻VKA⛐䓇䓊⇵⚃␐㗪ḇㅱ性⃵ἧ AF⎰Ἕ㚱ら⿏儓䗌か侭ᷳᷕ桐枸旚炻᷎㰺㚱䈡 䓐炻⚈℞㚱忈ㆸ偶⃺↢埨䘬⌙晒⿏炻LMWH⛐ ⭂䘬㸾⇯2ˤ⺢嬘␴䤆䴻䥹ˣ⽫冇䥹冯儓䗌⮰䥹 忁⸦ᾳ㗪㛇㗗ᶨᾳ㭼庫⬱ℐ䘬怠枭78ˤ 慓ⷓᶨ崟⎰ἄ䄏嬟炻天侫慷䘬㕡朊⊭㊔儓䗌䘬 LMWH᷎ᶵ㚫䨧德偶䚌炻侴ᶼ᷎䃉屯㕁栗 ✳ン冯♜慵⹎ˣ䈡⭂儓䗌䚠斄䘬埨㞻冯↢埨桐 䣢℞㚫忈ㆸ䔠偶ㆾ⡆≈偶⃺↢埨桐晒ˤ⎎⢾炻 晒姽Ộˣㇳ埻暨天冯⏎ˣ儓䗌䓐喍冯㈿ↅ埨∹ 䓙㕤LMWH⛐㆟⫽㗪ẋ嫅忇⹎嬲⾓炻⎗傥暨天 ᷳ攻䘬ṌḺἄ䓐ˣ儓䗌䓐喍㗗⏎忈ㆸ埨㵚ↅ普 㗪㗪㟡㒂橼慵冯anti-Xa䘬埨ᷕ㽫⹎(䚖㧁㗗㲐 䔘ⷠ(⤪埨⮷㜧Ỷᶳ)䫱䫱88, 89ˤ ⮬4-6⮷㗪ᷳ⼴忼⇘0.8-1.2 U/mL)Ἦ⡆≈∹慷ˤ 䓙㕤NOACἧ䓐⛐ら⿏儓䗌か侭幓ᶲ䘬嫱 UFHḇᶵ㚫䨧德偶䚌炻Ữ㗗UFH㚱忈ㆸ埨⮷㜧 㒂庫⮹炻䚖⇵⮵㕤ら⿏儓䗌か侭䘬㧁㸾㈿ↅ埨 Ỷᶳ冯橐岒䔷檮䘬桐晒炻侴ᶼ⎴㧋㚱暨天㗪㗪 ∹怠㑯ṵ㗗ẍVKAㆾ㗗LMWH䁢ᷣˤỮ㗗ᶨṃ 㟡㒂aPTT䘬㔠ῤ(䚖㧁㗗㲐⮬6⮷㗪ᷳ⼴忼㬋ⷠ 奨⮇⿏䞼䨞⛐↮㜸NOAC䓐㕤ら⿏儓䗌䘬㓰㝄 aPTTῤ䘬ℑ᾵)Ἦ⡆≈∹慷ˤ䓊⼴⒢ḛ㕡朊炻 冯⬱ℐ⿏㗪炻䘤䎦⛐AF⎰Ἕら⿏儓䗌㗪NOAC 屯㕁栗䣢VKAㆾ㗗LMWH⮵⒢ḛ⫘⃺㗗⬱ℐ䘬 ḇ姙㗗ᶨᾳ⎰䎮䘬㈿ↅ埨∹怠枭ˤᷡ湍ᶨᾳ⣏ 82, 83ˤ䓙㕤仢᷷NOACs䚠斄屯㕁炻㓭ᶵ⺢嬘⛐ ✳䞼䨞㭼庫㚱ら⿏儓䗌冯䃉ら⿏儓䗌䘬AFか侭

156 ϛॳႱ٩ݽᕛࡾЕޱᡊᆰᠬଢ଼௉ܘᏗՖᏘҢܻЖתᏘο݈תŌࡼڼߨᆰт

ἧ䓐NOAC䘬ᶨ⸜埨㞻冯↢埨桐晒炻䳸㝄䘤䎦 昌Ḯ埨㞻冯↢埨桐晒姽Ộᷳ⢾炻Ṏ⊭㊔㇨怠㑯 ⛐NOAC䘬ἧ䓐ᷳᶳ炻㚱ら⿏儓䗌侭᷎㰺㚱㭼 喍䈑䘬喍䈑≽≃⬠炻㗗⏎䴻偅冇愝䳈ẋ嫅ㆾ㳣 庫⣂䘬埨㞻冯↢埨ḳẞ90ˤ伶⚳⎎ᶨᾳ⣏✳䞼 ⊾92ˤ 䨞⇯㗗㭼庫NOAC冯warfarin⛐AF⎰Ἕら⿏儓䗌 䓙㕤仢⮹䚠斄䘬冐⸲娎槿炻䚖⇵⮵㕤AF か侭幓ᶲἧ䓐⼴䘬埨㞻冯↢埨ね⼊炻䳸㝄䘤䎦 ⎰Ἕ偅冇䕦か侭ᷳᷕ桐枸旚炻᷎㰺㚱䈡⭂䘬 NOAC䘬ἧ䓐␴warfarin䚠㭼炻㚱庫Ỷ䘬↢埨ḳ 㸾⇯ˤ⎘䀋⣂ᷕ⽫⚆㹗⿏䞼䨞栗䣢炻⛐≥ 65㬚 ẞ冯䚠Ụ䘬仢埨⿏ᷕ桐ḳẞ桐晒91ˤ 䘬AF⎰Ἕ偅冇䕦䕭(ASTㆾ㗗ALT⣏㕤㬋ⷠῤ ㈿ↅ埨∹ἧ䓐冯⏎ẍ⍲℞䧖栆䘬怠㑯䓐⛐ ᶲ旸䘬ℑ᾵ㆾ㗗total bilirubin⣏㕤㬋ⷠῤᶲ旸 AF⎰Ἕ㚱ら⿏儓䗌か侭ᷳᷕ桐枸旚炻暨天㚜⣂ 䘬1.5᾵)か侭(n = 633)ᷳᷕ炻ἧ䓐NOAC冯ἧ䓐 䘬䞼䨞屯㕁Ἦ㰢⭂ˤ warfarin䘬Ṣ䚠㭼炻℞ᷕ桐冯℞Ṿ埨㞻ḳẞˣ♜ ⺢嬘烉 慵↢埨ẍ⍲儠偫忻↢埨ḳẞ䘬桐晒㰺㚱ⶖ䔘炻 (1) AF⎰Ἕら⿏儓䗌䘬か侭⺢嬘␴䤆䴻䥹ˣ⽫ ᶼ㚱栗叿庫Ỷ䘬㬣ṉ䌯94ˤ 冇䥹冯儓䗌⮰䥹慓ⷓᶨ崟⎰ἄ䄏嬟㰢⭂㱣䗪 劍姽Ộ⇑⺲⼴炻娵䁢暨天攳䩳㈿ↅ埨∹炻 㕡憅炻天侫慷䘬㕡朊⊭㊔儓䗌䘬✳ン冯♜慵 伶⚳FDA (Food and Drug Administration) 冯㫸䚇 ⹎ˣ䈡⭂儓䗌䚠斄䘬埨㞻冯↢埨桐晒姽Ộˣ EMA (European Medicines Agency)㚱ὅ偅冇䕦 ㇳ埻暨天冯⏎ˣ儓䗌䓐喍冯㈿ↅ埨∹ᷳ攻䘬 䕭♜慵⹎(堐7)ᶵ⎴㇨⺢嬘䘬㈿ↅ埨∹攳䩳㕡㱽 ṌḺἄ䓐ˣ儓䗌䓐喍㗗⏎忈ㆸ埨㵚ↅ普䔘ⷠ ⤪堐8 92炻攳䩳NOACsᷳ⇵枰⃰姽Ộか侭䘬偅冇 (⤪埨⮷㜧Ỷᶳ)䫱(Class I, Level of Evidence ≇傥炻攳䩳NOACsᷳ⼴军⮹㭷⸜ᶨ㫉㚧か侭姽 C-EO)ˤ Ộ℞偅≇傥1ˤ ⺢嬘烉 ᠚ (1) ♜慵䘬偅冇䕦䕭㇨忈ㆸ䘬埨㵚䔘ⷠ炻⎴㗪ⷞمځݷȗłŇӫޑחᖝޟĶįĴġġ੫ۡ ੽੾ Ἦ埨㞻㞻⠆冯↢埨䘬檀桐晒炽⛐㚧AF⎰Ἕ 忶⍣娵䁢䔞偅冇䕦䕭⶚忈ㆸↅ埨≇傥Ỷᶳ 偅冇䕦䕭䘬か侭㒔⭂ᷕ桐䘬枸旚䫾䔍㗪炻天 㗪⎗ẍⷞἮ庫Ỷ䘬埨㞻㞻⠆ね⼊炻忁ᾳ婾溆⶚ 侫慷䘬昌Ḯ偅冇䕦䕭䘬♜慵⹎冯埨㞻/↢埨 䴻塓姙⣂㕘冰䘬嫱㒂㍐侣92ˤ冐⸲䞼䨞䘤䎦炻 桐晒⸛堉姽Ộᷳ⢾炻怬⊭㊔㇨怠㑯䘬喍䈑 ♜慵䘬偅冇䕦䕭㇨忈ㆸ䘬埨㵚䔘ⷠ炻㗗㚫⎴㗪 ℞暨䴻偅冇愝䳈ẋ嫅ㆾ㳣⊾䘬喍䈑≽≃⬠ ⷞἮ埨㞻㞻⠆冯↢埨䘬檀桐晒93ˤAF⎰Ἕ偅冇 (Class I, Level of Evidence C-EO)ˤ 䕦䕭䘬か侭㒔⭂ᷕ桐䘬枸旚䫾䔍㗪炻天侫慷䘬 (2) 攳䩳 NOACᷳ⇵枰⃰姽Ộか侭䘬偅冇≇傥炻

堐7ˢChild-Pugh Scoreẍ⍲偅冇䕦䕭♜慵⹎姽慷

Child-Pugh Score Measure 1 point 2 points 3 points Total bilirubin, mg/dL < 2 2-3 > 3 Serum albumin, g/dL > 3.5 2.8-3.5 < 2.8 INR < 1.7 1.7-2.3 > 2.3 Ascites None Mild Mod/Severe Encephalopathy None Grade I-II Grade III-IV Liver disease severity Severity Child-Pugh A Child-Pugh B Child-Pugh C Points 5-6 7-9 10-15

157 ϛॳႱ٩ݽᕛࡾЕޱᡊᆰᠬଢ଼௉ܘᏗՖᏘҢܻЖתᏘο݈תŌࡼڼߨᆰт

堐8ˢὅ偅冇䕦䕭♜慵⹎䘬㈿ↅ埨∹䓐㱽⺢嬘

Child- Warfarin Dabigatran Rivaroxaban Apixaban Edoxaban Pugh Category

FDA EMA FDA EMA FDA EMA FDA EMA FDA EMA

A INR INR ∹慷ᶵ暨 劍AST/ALT ∹慷ᶵ暨 ∹慷ᶵ暨 ∹慷ᶵ暨 嫡ヶἧ䓐 ∹慷ᶵ暨 ∹慷ᶵ暨婧㔜 (5-6↮) 䚖㧁ῤ 䚖㧁ῤ 婧㔜 > 2X ULNㆾ 婧㔜 婧㔜 婧㔜 ∹慷ᶵ暨 婧㔜 嫡ヶἧ䓐䈡⇍ 2-3 2-3 偅冇䕦䕭枸 婧㔜 㗗ASL/ALT > 妰㚫⼙枧⬀ 2X ULN 㳣䌯 ㆾ䷥入䲭䳈 > ᶵ⺢嬘ἧ䓐 1.5X ULN

B INR INR 嫡ヶἧ䓐 劍AST/ALT ᶵ⺢嬘ἧ ᶵ⺢嬘ἧ 嫡ヶἧ䓐 嫡ヶἧ䓐 ᶵ⺢嬘ἧ ∹慷ᶵ暨婧㔜 (7-9↮) 䚖㧁ῤ 䚖㧁ῤ ∹慷ᶵ暨 > 2X ULNㆾ 䓐 䓐 ∹慷ᶵ暨 ∹慷ᶵ暨 䓐 嫡ヶἧ䓐䈡⇍ 2-3 2-3 婧㔜 偅冇䕦䕭枸 婧㔜 婧㔜 㗗ASL/ALT > 妰㚫⼙枧⬀ 2X ULN 㳣䌯 ㆾ䷥入䲭䳈 > ᶵ⺢嬘ἧ䓐 1.5X ULN

C INR INR ᶵ⺢嬘ἧ 劍AST/ALT ᶵ⺢嬘ἧ ᶵ⺢嬘ἧ ᶵ⺢嬘ἧ ᶵ⺢嬘ἧ ᶵ⺢嬘ἧ ᶵ⺢嬘ἧ䓐 (10-15↮) 䚖㧁ῤ 䚖㧁ῤ 䓐 > 2X ULNㆾ 䓐 䓐 䓐 䓐 䓐 2-3 2-3 偅冇䕦䕭枸 妰㚫⼙枧⬀ 㳣䌯 ᶵ⺢嬘ἧ䓐

攳䩳NOACᷳ⼴军⮹㭷⸜ᶨ㫉㚧か侭姽Ộ℞ (edoxaban)䘬䞼䨞䳸㝄ᷕ䘤䎦炻CrCl > 95 mL/ 偅≇傥(Class I, Level of Evidence B-NR)ˤ min䘬AFか侭ἧ䓐edoxaban␴warfarin䚠㭼炻㚱 庫檀䘬ᷕ桐㭼ἳ53, 100ˤ ๫᠚ ⎘䀋ᾅ会⮵㕤NOACs㟡㒂僶冇≇傥䘬䴎ځݷȗłŇӫޑחᖝޟĶįĵġġ੫ۡ ੽੾ Ẁ㧁㸾炻昌Ḯῂ岜⎬ᾳNOAC䘬晐㨇暁䚚娎槿 僶冇䕦䕭㚫⡆≈AFか侭埨㞻㞻⠆ḳẞ䘬䘤 䳸㝄ᷳ⢾炻ḇ侫慷℞喍䈑≽≃⬠␴僶冇≇傥ᷳ 䓇䌯炻Ữ㗗ᷕ慵⹎䘬僶冇䕦䕭ḇ㗗↢埨䘬⌙晒 攻斄Ὢ䘬⮎槿䳸㝄炻⤪堐9ˤ ⚈⫸ᷳᶨ炻⽭枰⛐⎴㗪㚱㞻⠆冯↢埨䘬桐晒ᶳ 姙⣂䞼䨞⊭㊔⎘䀋‍ᾅ屯㕁⹓↮㜸栗䣢♜ ⍾⼿⸛堉ˤ⎎⢾炻㈿ↅ埨∹ㆾ⣂ㆾ⮹悥暨天僶 慵僶冇䕦䕭か侭䘬AF䘤䓇䌯㭼㬋ⷠṢ檀3, 104炻 冇ẋ嫅炻忁ṃ悥㗗㱣䗪AF⎰Ἕ僶冇䕦䕭㗪枰侫 Ữ㗗䓙㕤㈿ↅ埨∹⛐慵⹎僶冇䕦䕭(CrCl < 30 慷䘬⚈䳈3, 95, 96ˤ mL/min)ˣ㛓㛇僶冇䕦䕭(CrCl < 15 mL/min)␴暨 庽军ᷕ⹎䘬僶冇䕦䕭か侭(CrCl 30-89 mL/ 天㲿僶䘬AFか侭䚖⇵怬㰺㚱⣏✳䘬晐㨇暁䚚娎 min烊apixaban烉25-89 mL/min)⛐⚃ᾳNOACs 槿䳸㝄䘤堐炻⚈㬌⛐忁佌AFか侭䘬ᷕ桐枸旚䫾 䘬AF冐⸲娎槿ᷕ悥㚱塓䲵ℍ(堐3)炻䳸㝄栗 䔍ᶲ㰺㚱䈡⭂䘬㸾⇯炻暨姽Ộか侭㞻⠆冯↢埨 䣢炻NOACs␴warfarin⛐庽ᷕ⹎僶冇䕦䕭か 䘬桐晒炻ẍ⍲㇨怠㑯䘬喍䈑䴻䓙僶冇ẋ嫅䘬䉨 侭ᷳ枸旚ᷕ桐䘬㓰≃冯⬱ℐ⿏䘬㭼庫䳸㝄␴ 㱩Ἦ㰢⭂㱣䗪䫾䔍ˤ ⛐㬋ⷠ僶冇≇傥䘬か侭㗗䚠Ụ䘬97-102炻䓂军 ᷡ湍䘬ᶨᾳ⣏✳⚳⭞慓䗪屯㕁⹓↮㜸䞼 ARISTOTLE (apixaban)䘬娎槿䳸㝄栗䣢炻CrCl 䨞栗䣢105炻⛐AF⎰Ἕㄊ⿏僶冇䕭(n = 11,128)ᶼ

崲Ỷ䘬ね⼊ᶳ炻apixaban䘬⬱ℐ⿏堐䎦⯙崲栗 CHA2DS2VASc score ≥ 2䘬か侭炻␴㰺㚱ἧ䓐 叿⃒㕤warfarin99-103ˤ⚈㬌炻AF⎰Ἕ庽ᷕ⹎䘬僶 䘬Ṣ䚠㭼炻ἧ䓐warfarin侭䘤䓇农␥ᷕ桐冯农 冇䕦䕭か侭攳䩳NOAC䘬侫慷ㅱ␴㬋ⷠ僶≇傥 ␥↢埨ˣ⽫埨䭉䕦䕭⮶农㬣ṉẍ⍲ảỽ⍇⚈ 䘬か侭䃉䔘ˤ⎎⢾炻⛐ENGAGE AF-TIMI 48 忈ㆸ㬣ṉᷳ桐晒庫Ỷˤ侴AF⎰Ἕ㛓㛇僶冇䕭

158 ϛॳႱ٩ݽᕛࡾЕޱᡊᆰᠬଢ଼௉ܘᏗՖᏘҢܻЖתᏘο݈תŌࡼڼߨᆰт

堐9ˢ⎬ᾳNOAC娎槿ᷕ␴僶冇≇傥䚠斄䘬屯㕁冯⎘䀋‍ᾅ会㟡㒂僶≇傥䘬㌺昌㧁㸾

Dabigatran Rivaroxaban Apixaban Edoxaban (RE-LY) (ROCKET-AF) (ARISTOTLE) (ENGAGE AF-TIMI 48)

僶冇⹻㶭䌯 80% 35% 25% 50% 晐㨇暁䚚冐⸲娎 < 30 mL/min < 30 mL/min < 25 mL/min < 30 mL/min 槿ᷕㄊ⿏僶䕭㌺ 昌㡅ẞ(CrCl) ㄊ⿏僶䕭∹慷婧 䃉 15 mg ᶨ⣑ᶨ㫉 2.5 mg ᶨ⣑ℑ㫉 30 mg ᶨ⣑ᶨ㫉 㔜⺢嬘 劍CrCl 30-49 mL/ 劍serum creatinine ≥ 劍CrCl 30-49 mL/ min 1.5 mg/dL min

⎘䀋‍ᾅ会䴎Ẁ < 30 mL/min < 15 mL/min < 15 mL/min < 15 or > 95 mL/min 㟡㒂僶≇傥䘬㌺ 昌㧁㸾(CrCl)* *㬌㧁㸾ᷣ天㗗ὅ㒂⎬ᾳ喍䈑␴僶≇傥䚠斄䘬喍䈑≽≃⬠屯㕁

暨㲿僶(n = 1,728)ᶼCHA2DS2VASc score ≥ 2䘬 NOAC⼴㭷⸜军⮹姽Ộᶨ㫉僶冇≇傥(Class I, か侭炻ἧ䓐warfarin䘬Ṣ㚱庫Ỷ䘬ảỽ⍇⚈忈 Level of Evidence B-NR)ˤ ㆸ㬣ṉᷳ桐晒ˤ⎎ᶨᾳ伶⚳䘬⣏✳⚳⭞慓䗪屯 (2) AF⎰Ἕᷕ慵⹎䘬僶冇䕦䕭(CrCl 30-49 mL/ 㕁⹓↮㜸䞼䨞106 ⇯㗗㭼庫apixaban␴warfarin min; apixaban: serum creatinine ≥ 1.5 mg/dL ) ⛐AF⎰Ἕ㛓㛇僶冇䕭暨㲿僶䘬か侭幓ᶲ䘬堐 䘬か侭攳䩳NOAC㗪炻⺢嬘怠㑯庫Ỷ䘬∹慷 䎦ˤ䞼䨞栗䣢apixaban䳬(n = 2,351)␴warfarin (Class IIb, Level of Evidence B-R)ˤ 䳬(n = 23,172)䚠㭼炻ᷕ桐冯埨㞻ḳẞⶖᶵ⣂炻 (3) AF⎰Ἕ慵⹎僶冇䕦䕭(CrCl < 30 mL/min)ˣ㛓 Ữ㗗♜慵↢埨ḳẞ栗叿庫Ỷ烊⎎⢾炻apixaban 㛇僶冇䕦䕭(CrCl < 15 mL/min)␴暨天㲿僶䘬 5 mg䳬炻ᶵ䭉㗗␴2.5 mg䳬ㆾ㗗warfarin䳬䚠 か侭炻ㅱ㟡㒂℞埨㞻/↢埨䘬桐晒姽Ộ炻㰢 㭼炻䘮㚱栗叿庫Ỷ䘬ᷕ桐冯埨㞻ḳẞ冯㬣ṉ ⭂㗗⏎攳䩳warfarinㆾ㗗apixaban (Class IIb, 䌯ˤ ⚈㬌炻㟡㒂ᶲ徘ℑᾳ䞼䨞䳸㝄炻2019⸜伶 Level of Evidence B-NR)ˤ ⚳AHA䘬㱣䗪㊯⺽㊯䣢1炻⛐AF⎰Ἕ㛓㛇僶冇 (4) AF⎰Ἕ㛓㛇僶冇䕦䕭(CrCl < 15 mL/min)␴

䕭暨㲿僶䘬か侭ᶼCHA2DS2VASc score ≥ 2㗪炻 暨㲿僶䘬か侭炻ᶵ⺢嬘攳䩳dabigatranˣ ἧ䓐warfarinㆾ㗗apixaban㗗⎗ẍ侫ㄖ䘬ˤ䚖⇵ rivaroxabanˣㆾ㗗edoxaban (Class III, Level apixabanἧ䓐⛐AF⎰Ἕ㛓㛇僶冇䕭暨㲿僶䘬か of Evidence C-EO) ˤ 侭㚱ℑᾳ㬋忚埴ᷕ䘬晐㨇冐⸲娎槿炻AXADIA ޱԑߝޟݷȗłŇޑחᖝޟStudy (NCT02933697)ẍ⍲RENAL-AL Study ĶįĶġ੫ۡ (NCT02942407)ˤ 忁墉䘬⸜攟侭⭂佑䁢≥ 75㬚炻檀漉ḇ㗗ᶨ 㚵䓐㈿ↅ埨∹䘬AFか侭炻攳䩳⇵天姽Ộか ᾳ⎴㗪㚫⡆≈埨㞻㞻⠆冯↢埨桐晒䘬䈡⭂䉨 侭僶≇傥炻攳䩳⼴军⮹㭷⸜㩊槿ᶨ㫉僶≇傥炻 㱩ˤ䓙㕤AF䘬⸜攟侭℞埨㞻㞻⠆桐晒䘬ᶲ⋯ 夾暨天Ἦ婧㔜喍䈑䧖栆ㆾ∹慷ˤ堐10䁢ὅ僶冇 栗叿檀㕤↢埨桐晒䘬ᶲ⋯炻侴ἧ䓐⎋㚵㈿ↅ埨 䕦䕭♜慵⹎ᶵ⎴㇨⺢嬘䘬㈿ↅ埨∹攳䩳㕡㱽2, 5, ∹⎗ẍ㚱㓰枸旚埨㞻㞻⠆炻㓭⌛ἧ䘬䡢㭼⸜庽 9ˤ か侭㚱ῷ檀䘬↢埨桐晒炻Ữ㗗␴㰺㚱ἧ䓐喍䈑 ⺢嬘烉 䚠㭼炻⎋㚵㈿ↅ埨∹⛐AF䘬⸜攟侭䷥㓰䙲(net (1) 攳䩳 NOAC⇵枰⃰姽Ộ僶冇≇傥炻攳䩳 benefit: efficacy/bleeding safety balance)䘬ᶲ⋯㗗

159 ϛॳႱ٩ݽᕛࡾЕޱᡊᆰᠬଢ଼௉ܘᏗՖᏘҢܻЖתᏘο݈תŌࡼڼߨᆰт

堐10ˢὅ僶冇䕦䕭♜慵⹎ᶵ⎴㇨⺢嬘䘬NOACs攳䩳㕡㱽

Creatinine Dabigatran Rivaroxaban Apixaban Edoxaban Clearance

僶冇⹻㶭䌯 150 mg 15/20 mg 5 mgᶨ⣑ℑ㫉 60 mgᶨ⣑ᶨ㫉* CrCl ≥ 50 mL/ ᶨ⣑ℑ㫉 ᶨ⣑ᶨ㫉 2.5 mgᶨ⣑ℑ㫉 劍ẍᶳảᶨ㡅ẞ⬀⛐, min 劍ẍᶳảℑᾳ㡅ẞ⬀⛐: ∹慷暨㷃⋲: ⸜漉≥ 80㬚 橼慵≤ 60 kg 橼慵≤ 60 kg CrCl: 15-50 ml/min Creatinine ≥ 1.5 mg/dL ⎴㗪ἧ䓐P-gp inhibitor 喍䈑

僶冇⹻㶭䌯 110 mg 10/15 mg 5 mgᶨ⣑ℑ㫉 30 mg CrCl 30-49 ᶨ⣑ℑ㫉 ᶨ⣑ᶨ㫉 2.5 mgᶨ⣑ℑ㫉 ᶨ⣑ᶨ㫉 mL/min Or 劍ẍᶳảℑᾳ㡅ẞ⬀⛐: 150 mg ⸜漉≥ 80㬚 ᶨ⣑ℑ㫉 橼慵≤ 60 kg Creatinine ≥ 1.5 mg/dL

僶冇⹻㶭䌯 ᶵ⎗ἧ䓐 10/15 mg 2.5 mg 30 mg CrCl 15-29 ᶨ⣑ᶨ㫉 ᶨ⣑ℑ㫉 ᶨ⣑ᶨ㫉 mL/min

僶冇⹻㶭䌯 ᶵ⎗ἧ䓐 ᶵ⎗ἧ䓐 ᶵ⎗ἧ䓐 ᶵ⎗ἧ䓐 CrCl < 15 mL/ min or under dialysis

*劍 > 95 mL/minᶵ⎗ἧ䓐

⣂㕤⸜庽侭䘬107-112ˤ⍰NOAC䘬䷥㓰䙲⛐AF䘬 か侭䘬ᷕ桐桐晒⍲⎋㚵㈿ↅ埨∹䘬㓰䙲119炻䳸 ⸜攟侭㗗⃒㕤warfarin䘬(堐11)113-118ˤ 㝄栗䣢≥ 90㬚⎰ἝAF (n = 11,064)␴朆AF䘬か侭 堐ᷕ⎗ẍ䚳⇘⮵㕤AF䘬⸜攟侭炻㈿ↅ埨∹ (n = 14,658)䚠㭼炻㚱栗叿庫檀䘬儎㠿⠆ᷕ桐Ữ 䘬㓰≃冯⬱ℐ⿏⃒㕤㈿埨⮷㜧喍䈑烊侴NOAC 䚠Ụ䘬儎↢埨桐晒炽侴⛐≥ 90㬚⎰ἝAF䘬か侭 ⍰⃒㕤warfarinˤῤ⼿㲐シ䘬㗗炻dabigatran 150 ᷕ炻ἧ䓐warfarin (n = 617) ␴䃉ἧ䓐侭䚠㭼炻㚱 mg␴warfarin䚠㭼㚱庫檀䘬↢埨桐晒⎒旸㕤栙 栗叿庫Ỷ䘬儎㠿⠆ᷕ桐冯䚠Ụ䘬儎↢埨桐晒ˤ ⢾↢埨䘬悐↮炻侴儎↢埨䘬桐晒⛐110␴150 mg ⎎⢾炻ᶵ䭉㗗␴㰺㚱ἧ䓐ảỽ㈿埨㞻喍䈑炻ㆾ ℑᾳ∹慷悥㗗Ỷ㕤warfarin䳬䘬ˤApixaban⛐ 㗗ἧ䓐㈿埨⮷㜧喍䈑侭䚠㭼炻ἧ䓐warfarin侭℞ AF䘬⸜攟侭䘬堐䎦炻⇯㗗ᶵ䭉⛐埨㞻㞻⠆ḳẞ ䷥㓰䙲㗗ᶲ⋯䘬ˤ侴⛐≥ 90㬚⎰ἝAF䘬か侭炻 䘬枸旚㓰≃冯↢埨⬱ℐ⿏炻悥㗗⃒㕤warfarin ἧ䓐NOAC (n = 978)␴ἧ䓐warfarin (n = 768)䘬 䳬䘬炻⚈㬌℞䷥㓰䙲⛐⸜攟侭㗗⃒㕤庫⸜庽侭 㭼庫↮㜸䳸㝄忚ᶨ㬍栗䣢炻ἧ䓐NOAC䳬㚱栗 䘬炻暨㲐シ䘬㗗⛐ARISTOTLE娎槿ᷕ炻劍㚱ᶳ 叿庫Ỷ䘬儎↢埨冯䚠Ụ䘬儎㠿⠆ᷕ桐ˤ ↿ảℑᾳ⚈⫸⬀⛐烉⸜䲨 ≥ 80㬚炻橼慵 ≤ 60℔ 䧖䧖嫱㒂栗䣢NOAC⛐AF䘬⸜攟侭㗗ᶨ 㕌炻ㆾ㗗埨ᷕcreatinine ≥ 1.5 mg/dL炻apixaban∹ ᾳ㚱㓰⍰⬱ℐ䘬怠㑯炻ょ⛐侩⸜Ṣⷠ䘤䓇䘬僶 慷㗗㷃⋲䘬(2.5 mg bid)ˤ⎎ᶨᾳ⛐⸜攟侭⬱ℐ 冇≇傥ㆾ偅≇傥ᶳ旵天姀⼿↿ℍ喍䈑怠㑯䘬侫 ⿏堐䎦庫warfarinἛ䘬喍䈑㗗 edoxabanˤ 慷ˤ ᶨᾳ⎘䀋‍ᾅ屯㕁⹓䞼䨞↮㜸 ≥ 90㬚䘬AF ⺢嬘烉

160 ϛॳႱ٩ݽᕛࡾЕޱᡊᆰᠬଢ଼௉ܘᏗՖᏘҢܻЖתᏘο݈תŌࡼڼߨᆰт

堐11ˢ⎬ᾳ喍䈑⛐⣏✳AF晐㨇冐⸲娎槿ᷕ憅⮵⸜攟侭䘬堐䎦

娎槿⎵䧙 BAFTA SPAF II RE-LY ROCKET AF ARISTOTLE ENGAGE AF 䕭Ṣ㔠 973 385 7258 6229 5678 8474 ⸜漉 (⸜) ≥ 75 ≥ 75 ≥ 75 ≥ 75 ≥ 75 ≥ 75 喍䈑㭼庫 Warfarin vs. Warfarin vs. Dabigatran Rivaroxaban Apixaban Edoxaban aspirin 75 mg aspirin 325 110/150 mg 20 mg vs. 5 mg vs. 60 mg vs. mg vs. warfarin warfarin warfarin warfarin

徥希㗪攻 2.7⸜ 2.7⸜ 2⸜ 2⸜ 1.8⸜ 2.8⸜ ᷣ天䳸㝄 ᷕ桐/ℐ幓⿏ ᷕ桐 ᷕ桐/ℐ幓⿏ ᷕ桐/ℐ幓⿏ ᷕ桐/ℐ幓⿏ ᷕ桐/ℐ幓⿏ 㞻⠆ḳẞ/栙 㞻⠆ḳẞ 㞻⠆ḳẞ 㞻⠆ḳẞ 㞻⠆ḳẞ ℏ↢埨 ᷣ天䳸㝄ᷳ RR 0.48 3.6%⸜vs. D110 HR 0.80 HR 0.71 HR 0.83 䚠⮵桐晒 (0.28-0.80) 4.8%⸜ HR 0.88 (0.63-1.02) (0.53-0.95) (0.66-1.04) p = 0.39 (0.66-1.17) D150 HR 0.67 (0.63-1.02)

慵⣏↢埨ḳ 1.9%⸜vs. D110/150/ 4.9%⸜vs. 3.3%⸜vs. 4.0%⸜vs. ẞ 2.0%⸜ warfarin 4.4%⸜ 5.2%⸜ 4.8%⸜ p = 0.90 4.4/5.1/4.4% HR 1.11 p < 0.05 p < 0.05 ⸜ (0.92-1.34) D110 p = 0.89 D150 p =0.07

(1) ≥ 75㬚䘬AFか侭炻ㅱ侫ㄖἧ䓐⎋㚵㈿ↅ埨∹ 䞼䨞嫱㒂冯䚠斄㊯⺽悥Ὗ旸⛐ⅈ䉨≽傰䕦䕭炻 (warfarinㆾ㗗NOAC)Ἦ枸旚ᷕ桐炻᷎⮯侩⸜ AF⎰Ἕ柠≽傰冯栙ℏ≽傰䱍䉨䠔⊾䕦䕭⤪ỽ攳 Ṣⷠ⎰Ἕ䘬僶冇≇傥ᶳ旵炻↿ℍ喍䈑冯∹慷 䩳㈿埨㞻喍䈑䘬嫱㒂㚱⼭㛒Ἦ㚜⣂䘬䞼䨞ˤ⚈ 怠㑯䘬侫慷(Class I, Level of Evidence A)ˤ 㬌炻㬌嗽↿䘬⺢嬘㗗㟡㒂⽫冇䚠斄䞼䨞䳸㝄ẍ ⍲⎘䀋/伶⚳/㫸㳚⽫冇䚠斄⬠㚫↢䇰斄㕤ȾAF ଢ଼૕ ⎰Ἕ䨑⭂䘬ⅈ䉨≽傰䕦䕭ȿ炻ȾAF⎰Ἕ⿍⿏ⅈځݷȗłŇӫޑחᖝޟĶįķġġ੫ۡ ๔ޑ฽Ͻ੽੾ 䉨≽傰䕦䕭ȿẍ⍲ȾAF⎰Ἕ暨忚埴⽫⮶䭉㩊㞍 ≽傰䱍䉨䠔⊾䕦䕭ẍ⍲≽傰㓗㝞伖㓦埻炻 ㆾ䴻䙖ⅈ䉨≽傰ṳℍ㱣䗪㗪ȿᷳ㱣䗪㊯⺽1-3, 9, 忂ⷠ暨ἧ䓐㈿埨⮷㜧喍䈑Ἦ枸旚埨㞻㞻⠆ḳẞ 84ˤ ㆾ㓗㝞ℏ䘬埨㞻⼊ㆸˤ 奨⮇䞼䨞栗䣢炻⎰Ἕ柠 ≽傰䱍䉨䠔⊾㚫⡆≈AFか侭仢埨⿏ᷕ桐䘬桐晒 ĶįķįIJġġᢓѴᓛଢ଼૕੭બᇄՖᆓӔ೽ 120, 121炻侴AFḇ⡆≈柠≽傰䊡䨬ṳℍ冯ㇳ埻㱣䗪 ĩņŹŵųŢŤųŢůŪŢŭġŤŢųŰŵŪťġŴŵŦůŰŴŪŴġ 122 ŢůťġųŦŷŢŴŤŶŭŢųŪŻŢŵŪŰůĪ 㗪䘬Ἕ䘤䕯 ˤ⛐栙ℏ≽傰䱍䉨䠔⊾䘬奨⮇䞼 䨞⇯䘤䎦炻䔞AF䘬ᷕ桐か侭⎰Ἕ㚱栙ℏ≽傰䠔 ᶨᾳ剔嗕䘬⣂ᷕ⽫⚆㹗⿏䞼䨞126炻899⎵ ⊾䕦䕭㗪炻㛒Ἦ䘬埨䭉Ἕ䘤䕯冯㬣ṉ䌯䘮㚫ᶲ 仢埨⿏ᷕ桐ㆾTIA䘬AFか侭炻165⎵(18.3%)⎴ ⋯123-125ˤ 㗪⎰Ἕ≥ 50%䘬䕯䉨⿏柠≽傰䊡䨬炻冯仢᷷柠 䃞侴⣏悐↮AF⎰Ἕ≽傰䱍䉨䠔⊾䕦䕭䘬 ≽傰䊡䨬䘬か侭䚠㭼炻⸛⛯徥希3.5⸜炻℞仢

161 ϛॳႱ٩ݽᕛࡾЕޱᡊᆰᠬଢ଼௉ܘᏗՖᏘҢܻЖתᏘο݈תŌࡼڼߨᆰт

埨⿏ᷕ桐⽑䘤䘬桐晒㚜檀(21.2%㭼12.7%炻p = ᶨ枭杻⚳䘬䞼䨞131炻780⎵⸛⛯69.5㬚䘬AF

0.005)炻ḇ㚱庫檀䘬CHA2DS2VASc scores (4.3㭼 ᷕ桐か侭炻231⎵(29.6%)⎰Ἕ≥ 50%栙ℏ≽傰䊡

3.3炻p < 0.001)炻⣂嬲㔠↮㜸栗䣢炻⮵㕤㚱仢埨 䨬炻CHADS2 score冯栙ℏ䊡䨬䘬≽傰㔠䚖㚱㬋 ⿏ᷕ桐ㆾTIA䘬AFか侭炻⎰Ἕ≥ 50%䘬䕯䉨⿏柠 䚠斄(r = 0.187炻p < .001)ˤAFか侭䘤䓇仢埨⿏ᷕ ≽傰䊡䨬㗗仢埨⿏ᷕ桐⽑䘤冯30⣑㬣ṉ䌯䘬䌐 桐䘬㨇廱ᶵℐ䃞Ἦ冒⽫冇䉨㱩(⽫㇧ℏ㞻⫸ˣỶ 䩳⌙晒⚈⫸ˤ䚖⇵憅⮵㬌䉨㱩䘬冐⸲嗽伖仢᷷ ⶎ⽫俛埨㳩ˣⶎ⽫㇧冒䘤⿏⚆枛)炻ḇ⎗傥冯埨 冐⸲嫱㒂冯⣏✳䞼䨞炻㟡㒂2018⸜㫸㳚⽫冇⬠ 䭉䱍䉨≽傰䠔⊾㚱斄炻⊭⏓栙ℏ䊡䨬131ˣᷣ≽ 㚫⺢嬘2炻劍か侭⎰Ἕ䃉䕯䉨柠≽傰䊡䨬炻⎗ 傰⺻㔹⟲132ˣ柠≽傰䊡䨬133ˤ⎎ᶨᾳ杻⚳⚆㹗 夾䁢⎰Ἕ㚱䨑⭂ⅈ⽫䕯䘬か侭炻䴎Ḱstatin冯╖ ⿏䞼䨞炻401⎵仢埨⿏ᷕ桐か侭⎰Ἕ㚱⶚䞍ㆾ㕘 ᶨ⎋㚵㈿ↅ埨∹ˤ憅⮵㚱䕯䉨䘬柠≽傰䊡䨬炻 姢㕟AF134炻⮯ᷕ桐㨇廱↮䁢⽫冇䚠斄冯朆⽫冇

昌Ḯ䴎Ḱstatin㱣䗪⢾炻⎗侫ㄖ堉慷ᾳ⇍か侭⇑ 䚠斄⌙晒⚈⫸炻䘤䎦晐叿CHA2DS2VASc scores 䙲桐晒⼴炻↢埨桐晒䚠⮵庫⮷䘬か侭⎗侫ㄖ䞕 ↮㔠⡆≈炻ℑ侭䘬⌙晒⚈⫸㔠䚖䘮⡆≈炻⽫冇 㛇ἧ䓐╖ᶨ㈿埨⮷㜧喍䈑≈ᶲNOAC炻Ữṵ仢 䚠斄⌙晒⚈⫸冯㊩临✳AFˣ幓橼岒慷㊯㔠ˣ⽫ ᷷冐⸲嫱㒂᷎暨天㚜ᶨ忚㬍䞼䨞炻䚖⇵᷎ᶵ⺢ 堘䪕ˣⶎ⽫㇧䘬volume index䚠斄烊侴朆⽫冇䚠 嬘攟㛇⎴㗪䴎Ḱ㈿ↅ埨∹冯㈿⮷㜧喍䈑炻⚈℞ 斄⌙晒⚈⫸⸜漉ˣ檀埨⡻ˣ䱾⯧䕭ˣⅈ䉨≽傰 㚫⡆≈か侭↢埨桐晒ˤ 懋⊾㊯㔠䚠斄炻忶⍣䞼䨞䘬䡢栗䣢㚱悐↮⶚㚵 柠≽傰䊡䨬䘬埨䭉ℵ忂䗪㱽⊭㊔柠≽傰ℏ 䓐⎋㚵㈿ↅ埨∹䘬NVAFか侭ℵ䘤䓇仢埨⿏ᷕ 兄∅昌埻(carotid endarterectomy)冯柠≽傰㓗㝞 桐㗗冯朆⽫⚈⿏⌙晒⚈⫸㚱斄炻⊭⏓栙ℏ≽傰 伖㓦(carotid stenting)炻㟡㒂Cochrane㔯䌣⚆栏 䊡䨬135ˤ 127炻⿍⿏ᷕ桐か侭⎰ἝAF冯䕯䉨⿏♜慵柠≽傰 䚖⇵憅⮵朆⽫⚈⿏仢埨⿏ᷕ桐䘬枸旚㗗ἧ 䊡䨬炻埨䭉ℵ忂䘬㕡⺷庫⺢嬘ἧ䓐柠≽傰ℏ兄 䓐㈿埨⮷㜧喍䈑炻Ữ朊⮵仢埨⿏ᷕ桐ᶼ⎰Ἕ㚱 ∅昌埻炻䚠庫㕤柠≽傰㓗㝞伖㓦炻傥性⃵か侭 栙ℏ≽傰䊡䨬䘬AFか侭炻䚖⇵ṵ仢᷷冐⸲嫱㒂 ⽭枰⛐⎋㚵㈿ↅ埨∹ᷳ⢾炻柵⢾ἧ䓐暁慵㈿埨 冯⣏✳䞼䨞炻⎴㗪䴎Ḱ⎋㚵㈿ↅ埨∹冯㈿埨⮷ ⮷㜧喍䈑忚侴⡆≈慵⣏↢埨ḳẞ䘬桐晒ˤ䚖⇵ 㜧喍䈑ἄ䁢枸旚䓐喍炻攟㛇ἧ䓐㚫⡆≈↢埨桐 ㍍⍿柠≽傰㓗㝞伖㓦䘬AFか侭炻ṵ仢᷷冐⸲ 晒炻ㅱ侫慷ᾳ⇍か侭埨㞻桐晒冯↢埨桐晒⼴ℵ 嫱㒂冯⣏✳䞼䨞㍸ὃ㱣䗪⺢嬘炻⽫冇䥹柀➇⇯ 埴婧㔜䓐喍ˤ ⶚㚱RE-DUAL PCI (dabigatran 110/150 mg)128ˣ 㱣䗪㰢䫾⿅侫䘬慵溆⊭㊔烉AF忈ㆸ埨㞻㞻 PIONEER AF-PCI (rivaroxaban 15/10 mg)129 ⍲ ⠆䘬桐晒冯⎰Ἕ㈿埨⮷㜧∹㗪↢埨桐晒䘬⸛堉 AUGUSTUS (apixaban 5/2.5 mg)130 ᶱᾳ⣏✳䘬 姽Ộ烊≽傰䱍䉨䠔⊾䕦䕭㗗䨑⭂ㆾ朆䨑⭂(⿍ ⇵䝣⿏䞼䨞䘤堐℞䳸㝄(edoxaban䘬EDOX-APT ⿏ㆾㄊ⿏)䘬烊ẍ⍲Ἕ䓐㈿埨⮷㜧喍䈑䘬㊩临㗪 trial怬㛒䘤堐䳸㝄)炻憅⮵⿍⿏ⅈ⽫䕯か侭忚埴 攻ˤ ⅈ䉨≽傰㓗㝞伖㓦⼴ἧ䓐NOAC冯╖ᶨ㈿埨⮷ 䓙㕤䚠斄䞼䨞䳸㝄ᷕ䘬埨㞻㞻⠆ḳẞ⣒ 㜧喍䈑(忂ⷠ㗗clopidogrel)ㆾ⁛䴙VKA≈ᶲ暁慵 ⮹炻ẍ军㕤䴙妰㓰≃ᶵ嵛ẍ䡢⭂喍䈑㓰≃炻⎒ ㈿埨⮷㜧喍䈑䘬㓰㝄冯⬱ℐ⿏䘬㭼庫ˤNOAC 傥䡢⭂喍䈑䘬↢埨⬱ℐ⿏ˤ䚖⇵䘬嫱㒂栗䣢1-3, 9, 䳬⛐↢埨ḳẞ䘬⬱ℐ⿏ᶲ⛯⃒㕤⁛䴙ᶱ⎰ᶨㆾ 84, 128-131烉 暁㈿㱣䗪炻 ᶼ䘤䓇㞻⠆ḳẞ䘬桐晒䚠䔞ˤ (a) ⎋㚵㈿ↅ埨∹ (⊭㊔warfarinˣrivaroxabanˣ dabigatranㆾapixaban)Ἕ䓐ᶨ䧖㈿埨⮷㜧喍 Ķįķįijġġᢓϱଢ଼૕๔ޑଢ଼૕੭બ 䈑(clopidogrel)天㭼Ἕ䓐ℑ䧖㈿埨⮷㜧喍䈑 ĩŊůŵųŢŤųŢůŪŢŭġŢŵũŦųŰŴŤŭŦųŰŵŪŤġŴŵŦůŰŴŪŴĪ Ἦ䘬⬱ℐ炻↢埨桐晒庫Ỷˤ

162 ϛॳႱ٩ݽᕛࡾЕޱᡊᆰᠬଢ଼௉ܘᏗՖᏘҢܻЖתᏘο݈תŌࡼڼߨᆰт

(b) 劍㈿ↅ埨∹暨Ἕ䓐ᶨ䧖㈿埨⮷㜧喍䈑㗪炻 䈑炻㚫㭼Ἕ䓐ℑ䧖㈿埨⮷㜧喍䈑(clopidogrel clopidogrel㗗㭼aspirin⬱ℐ䘬怠㑯ˤ + aspirin)Ἦ䘬⬱ℐ炻㚱庫Ỷ䘬↢埨桐晒 (c) ㈿ↅ埨∹暨Ἕ䓐 aspirin㗪炻怠㑯Ỷ∹慷75- (Class IIa, Level of Evidence B-R)ˤ 100 mg㗗㭼庫⬱ℐ䘬怠㑯ˤ ໶ٱݧཎޟҢਢٺd) ㈿ↅ埨∹Ἕ䓐ℑ䧖㈿埨⮷㜧喍䈑㗪炻䚉慷ᶵ ķįġġŏŐłńŴ) 天崭忶4-6忙炻ẍ⃵⡆≈↢埨䘬桐晒ˤ ᇄŸŢųŧŢųŪůޟ৯౴ (e) 庫㕘䘬㈿埨⮷㜧喍䈑炻⁷㗗 ticagrelorẍ⍲ prasugrel冯㈿ↅ埨∹Ἕ䓐䘬↢埨⬱ℐ⿏怬㰺 ⛐⍇⥳䘬⚃䭯冐⸲䞼䨞(堐12)炻NOAC⛐ 㚱嵛⣈䘬嫱㒂Ἦ嫱㖶℞⬱ℐ⿏ˤ 枸旚ᷕ桐⍲ℐ幓⿏㞻⠆ḳẞ䘬㓰㝄炻昌ḮỶ ⺢嬘烉 ∹慷edoxaban 30 mg炻℞检䘮ᶵ≋㕤䓂军⃒㕤 (1) AF ⎰Ἕ≽傰䱍䉨䠔⊾䕦䕭䘬か侭炻劍 warfarinˤ⛐⬱ℐ⿏䘬㕡朊炻NOAC忈ㆸ慵⣏↢

CHA2DS2VASc ≥ 2↮㗪炻ㅱ攳䩳⎋㚵㈿ↅ埨 埨ḳẞ䘬桐晒ḇỶ㕤ㆾᶵ≋㕤warfarin炻↢埨 ∹Ἦ枸旚埨㞻ḳẞ(Class I, Level of Evidence ⿏ᷕ桐䘬桐晒⇯⏰䎦ᶨ农⿏䘬⃒㕤warfarinˤ B-R)ˤ ➢㕤ẍᶲ䎮䓙炻AHA 2019 focus update for (2) AF⎰Ἕ≽傰䱍䉨䠔⊾䕦䕭ㆾ㗗暨忚埴≽ management of patients with atrial fibrillation1 傰䊡䨬ṳℍ㱣䗪䘬か侭炻warfarinἝ䓐 ⺢嬘䃉⽫冇㨇㡘䒋兄伖㎃⍲䃉ᷕ慵⹎Ḵ⮾ clopidogrelᶨ䧖㈿埨⮷㜧喍䈑炻㚫㭼Ἕ䓐ℑ 䒋䊡䨬䘬AFか侭炻ἧ䓐NOACἄ䁢⃒⃰䘬 䧖㈿埨⮷㜧喍䈑(clopidogrel + aspirin)Ἦ䘬 枸旚㞻⠆喍䈑ˤ晾䃞NOAC⛐⬱ℐ⿏ᶲ⃒㕤 ⬱ℐ炻㚱庫Ỷ䘬↢埨桐晒(Class IIa, Level of warfarin炻ỮNOAC㖻↢䎦儠偫ᶵ怑䘬∗ἄ䓐炻 Evidence B-R)ˤ 䘤䓇儠偫忻↢埨䘬桐晒⛐ἧ䓐dabigatran 150 (3) AF⎰Ἕ≽傰䱍䉨䠔⊾䕦䕭ㆾ暨忚埴≽傰䊡 mgˣrivaroxabanˣedoxaban 60 mg栗叿檀㕤 䨬ṳℍ㱣䗪䘬か侭炻rivaroxabanˣdabigatran warfarinˤ ㆾapixabanἝ䓐clopidogrelᶨ䧖㈿埨⮷㜧喍 ⛐⎘䀋㛔⛘䘬䞼䨞炻ℑ䭯⇑䓐‍ᾅ屯㕁

堐12ˢ⎬NOACsᷳ⬱ℐ⿏冯㚱㓰⿏䘬䚠⮵桐晒㭼䌯

喍䈑 ᷕ桐冯ℐ幓 仢埨⿏ᷕ桐 ↢埨⿏ᷕ桐 ⽫倴㠿⠆ 慵⣏↢埨ḳ 儎↢埨 儠偫忻↢埨 ⿏㞻⠆ḳẞ ẞ Dabigatran 0.65* 0.76* 0.26* 1.27 0.94 0.42* 1.48* 150 mg (0.52-0.81) (0.59-0.97) (0.14-0.49) (0.94-1.71) (0.82-1.08) (0.29-0.61) (1.19-1.86) Dabigatran 0.89* 1.10 0.31* 1.29 0.80* 0.29* 1.04 110 mg (0.73-1.09) (0.88-1.37) (0.17-0.56) (0.96-1.75) (0.70-0.93) (0.19-0.45) (0.82-1.33) Rivaro- 0.88* 0.94 0.59* 0.81 1.04 0.67* 1.61* xaban (0.75-1.03) (0.75-1.17) (0.37-0.93) (0.63-1.06) (0.90-2.30) (0.47-0.93) (1.30-1.99) Apixaban 0.79* 0.92 0.51* 0.88 0.69* 0.42* 0.89 (0.66-0.95) (0.74-1.13) (0.35-0.75) (0.66-1.17) (0.60-0.80) (0.30-0.58) (0.70-1.15) Edoxaban 0.87* 1.00 0.54* 0.94 0.80* 0.47* 1.23* 60 mg (0.73-1.04) (0.83-1.19) (0.38-0.77) (0.74-1.19) (0.71-0.91) (0.34-0.63) (1.02-1.50) Edoxaban 1.13* 1.41* 0.33* 1.19 0.47* 0.30* 0.67* 30 mg (0.96-1.34) (1.19-1.67) (0.22-0.50) (0.95-1.49) (0.41-0.55) (0.21-0.43) (0.53-0.83) * p < 0.05, Dabigatran (RR), ℞检䁢(HR)ˤ

163 ϛॳႱ٩ݽᕛࡾЕޱᡊᆰᠬଢ଼௉ܘᏗՖᏘҢܻЖתᏘο݈תŌࡼڼߨᆰт

⹓㔠㒂䘬⚆㹗⿏䞼䨞10, 136炻忚埴Ḯ⎘䀋㕷佌ἧ database忚埴䘬㕷佌↮㜸栗䣢炻ἧ䓐dabigatran 䓐NOACs冯warfarin䘬㭼庫ˤ⛐仢埨⿏ᷕ桐冯 冯warfarin䘬⽫倴㠿⠆䘤䓇䌯㰺㚱䴙妰ᶲ䘬ⶖ䔘 ℐ幓⿏㞻⠆ḳẞˣ↢埨⿏ᷕ桐ˣ慵⣏↢埨ḳ (HR = 0.92炻0.78-1.08)ˤỮ⼴临䘬⣂䭯䞼䨞冯䴙 ẞˣ儠偫↢埨ˣ㬣ṉ䌯堐䎦䘮⃒㕤ㆾᶵṆ㕤 ⎰↮㜸⮵㕤NOAC㗗⏎㭼warfarin⭡㖻䘤䓇⽫倴 warfarin炻忁㧋䘬䳸㝄㓗㊩Ḯἧ䓐NOACἄ䁢⃒ 㠿⠆ṵ冲䛦婒䳃䳄炻㇨ẍ⛐⽫倴㠿⠆檀桐晒䘬 ⃰怠㑯䘬婾溆ˤ か侭ἧ䓐NOACṵ暨䈡⇍㲐シˤ ῤ⼿㲐シ䘬㗗炻晾䃞NOAC⛐冐⸲娎槿ᷕ 晾䃞NOAC冯℞Ṿ喍䈑ṌḺἄ䓐㭼warfarin 㚱⃒㕤warfarin䘬⬱ℐ⿏冯䚠Ụ䘬枸旚ᷕ桐㓰 ⮹炻Ữ㚱ṃ喍䈑ἧ䓐㗪ṵ⽭枰⮷⽫ˤ㟡㒂2018 㝄炻Ữᶵẋ堐㇨㚱⶚ἧ䓐warfarin䘬か侭悥枰廱 ⸜EHRA㱣䗪㊯⺽3 ↿冱⎰Ἕἧ䓐㚫忈ㆸNOAC ㎃䁢NOAC炻warfarin䘬time in therapeutic range 㽫⹎嬲⊾䘬喍䈑(堐13)ˤ (TTR)ㅱ娚↿䁢侫ㄖ⚈䳈ˤ⛐⍇⥳䘬晐㨇冐⸲ ㈿䘚䗯喍㗗ᷕ桐か侭ⷠ㚫冯NOACἝ 娎槿ᷕ炻RE-LY䘬TTR䁢64%炻ROCKET-AF䁢 䓐䘬喍䈑炻姙⣂㈿䘚䗯喍㚫Ὣ忚CYP3A4⍲ 55%炻ARISTOTLE䁢62%炻ENGAGE䁢65%炻 p-glycoprotein䘬ἄ䓐炻ἧNOAC埨ᷕ㽫⹎ᶳ 㚱ṃ⮰⭞娵䁢劍傥䵕㊩䨑⭂ᶼ列⤥䘬TTR (≥ 旵ˤ䚖⇵᷎䃉冐⸲娎槿屯㕁炻Ữ㟡㒂⎬⭞ầ╖ 65%)炻NOACᶵᶨ⭂㖶栗⃒㕤warfarin137, 138炻⚈ 冯⮰⭞シ夳炻carbamazepineˣoxcarbazepineˣ 㬌⛐INR㍏⇞列⤥䘬䕭か炻⎗ẍ侫ㄖ两临ἧ䓐 topiramateˣlevetiracetamˣphenobarbitalˣ warfarinˤ phenytoinˣvalproic acid悥㚫旵ỶNOAC喍䈑 NOAC㗗⏎㭼warfarin⭡㖻䘤䓇⽫倴㠿⠆炻 㽫⹎炻Ἕ䓐㗪ㅱ娚⮷⽫ㆾ性⃵ˤ㟡㒂2018⸜ ṵ冲㗗ᶨᾳ℟䇕嬘䘬⓷柴ˤ㟡㒂RE-LY䘬䞼䨞 EHRA㱣䗪㊯⺽↿冱㈿䘚䗯喍冯NOAC䘬ṌḺ 䳸㝄栗䣢炻ἧ䓐dabigatran䘤䓇⽫倴㠿⠆䘬⎗ ἄ䓐(堐14)ˤ 傥⿏䔍檀㕤warfarin (RR = 1.38炻1.00-1.91)炻 Dabigatranἧ䓐㗪⽭枰㔜䰺⏆㚵炻ᶵ⎗⮯先 侴⛐℞Ṿ䘬factor Xa inhibitor᷎ᷕ䃉栗叿䘬 ♲⺬䟜ˣ␨♤ㆾㇻ攳炻⏎⇯䓇橼⎗䓐䌯㚫庫㧁 䴙妰シ佑ˤ䃞侴⛐FDA 2014⸜⇑䓐Medicare 㸾先♲∹✳⡆≈75%炻侴rivaroxaban, apixaban,

堐13ˢ喍䈑⎰Ἕἧ䓐㚫忈ㆸNOAC㽫⹎嬲⊾

栗叿⡆≈喍䈑㽫⹎炻 栗叿㷃⮹喍䈑㽫⹎炻 㚫⡆≈喍䈑㽫⹎炻ㅱ㷃⮹ ᶵㅱἝ䓐 ᶵㅱἝ䓐 喍䈑∹慷᷎⮷⽫ἧ䓐

Dabigatran dronedarone, ketoconazole, rifampin, St John's wort amiodarone, quinidine, itraconazole, voriconazole verapamil, clarithromycin, erythromycin

Rivaroxaban dronedarone, ketoconazole, rifampin, St John's wort amiodarone, quinidine, itraconazole, voriconazole, verapamil, clarithromycin, ritonavir (anti-HIV喍䈑) erythromycin

Apixaban ritonavir, ketoconazole, rifampin, St John's wort amiodarone, dronedarone, itraconazole, voriconazole diltiazem, clarithromycin, erythromycin, naproxen

Edoxaban St John's wort (⎗傥⎗ẍ冯 dronedarone, ketoconazole, rifampinἝ䓐) itraconazole, voriconazole, clarithromycin, erythromycin

164 ϛॳႱ٩ݽᕛࡾЕޱᡊᆰᠬଢ଼௉ܘᏗՖᏘҢܻЖתᏘο݈תŌࡼڼߨᆰт

堐14ˢ㈿䘚䗯喍冯NOAC䘬ṌḺἄ䓐

Dabigatran Rivaroxaban Apixaban Edoxaban Carbamazepine 䤩⽴ 嫡ヶㆾ性⃵ 嫡ヶㆾ性⃵ 䤩⽴ Oxcarbazepine 嫡ヶㆾ性⃵ 嫡ヶㆾ性⃵ Ethosuximide Gabapentin Pregabalin Lamotrigine Levetiracetam 䤩⽴ 䤩⽴ 䤩⽴ 䤩⽴ Phenobarbital 䤩⽴ 嫡ヶㆾ性⃵ 嫡ヶㆾ性⃵ 䤩⽴ Phenytoin 䤩⽴ 嫡ヶㆾ性⃵ 嫡ヶㆾ性⃵ 䤩⽴ Topiramate 嫡ヶㆾ性⃵ 嫡ヶㆾ性⃵ Valproic acid 䤩⽴ 䤩⽴ 䤩⽴ 䤩⽴ Zonisamide edoxaban㗗⎗ẍ䢐䰱⍲䭉㿴䘬ˤ䓙㕤姙⣂ᷕ桐 堐15ˢỶ↢埨桐晒ㇳ埻NOAC 喍⺢嬘㗪攻

か侭⽭枰ἧ䓐滣偫䭉㿴梇炻ἧ䓐ᶲ⽭枰㲐シˤ CrCl Dabigatran Factor Xa 劍㚵䓐NOAC䘬か侭↢䎦↢埨ㆾ㗗暨 inhibitor 天忚埴䵲⿍ㇳ埻㗪炻dabigatran䘬⍵廱∹ ≥ 80 mL/min 24⮷㗪ẍᶲ 24⮷㗪ẍᶲ idarucizumab⶚䴻ᶲⶪ炻侴factor Xa inhibitor䘬 50–79 mL/min 36⮷㗪ẍᶲ 24⮷㗪ẍᶲ ⍵廱∹andexanet-α⛐⎘䀋⯂㛒㟠⎗冐⸲ἧ䓐炻 30–49 mL/min 48⮷㗪ẍᶲ 24⮷㗪ẍᶲ ⛐⍵廱∹䃉㱽䩳⌛⍾⼿䘬ね㱩ᶳ炻⎗ẍ侫ㄖ 15–29 mL/min ᶵ⺢嬘ἧ䓐 36⮷㗪ẍᶲ ἧ䓐PCCˤ劍㗗忚埴朆䵲⿍䘬枸⭂ㇳ埻㗪炻 < 15 mL/min ᶵ⺢嬘ἧ䓐 ᶵ⺢嬘ἧ䓐 NOAC䘬 䓐㗪攻冯ㇳ埻埻⺷ˣ僶≇傥㚱斄 Ὢ炻㟡㒂2018⸜EHRA㱣䗪㊯⺽⺢嬘⤪ᶳ2烉 䨧⇢ˣ傠僼儡僼ㇳ埻ˣ偅冇僶冇↯䇯ˣ䴻⯧ (a) ↢埨桐晒㤝Ỷ䘬ㇳ埻 (minor bleeding risk)烉 忻㓅嬟儢⇖昌ˣ橼⢾暯㲊䠶䞛ˣ橐䥹ㇳ埻 ⊭㊔㉼䈁ˣ㢵䈁䫱䈁䥹ㇳ埻ˣ䘥ℏ晄ㇳ埻ˣ 䫱䫱ˤ㟡㒂僶≇傥ᶵ⎴炻 喍⺢嬘㗪攻⤪堐 曺⃱䛤ㇳ埻ˣℏ夾掉㩊㞍ˣ䙖兂堐㶢ㇳ埻䫱 16ˤ 䫱ˤ忁ṃㇳ埻⇵⸦⣑ᶵ䓐 㬊㚵䓐NOAC炻 堐16ˢ檀↢埨桐晒ㇳ埻NOAC 喍⺢嬘㗪攻 ㇳ埻䔞⣑㖑ᶲ嶛忶ᶨ㫉㚵喍炻ㇳ埻⬴ㆸ⼴6 CrCl Dabigatran Factor Xa ⮷㗪㰺㚱㖶栗↢埨ὧ⎗ẍ两临㬋ⷠ㚵喍ˤ inhibitor (b) Ỷ↢埨桐晒䘬ㇳ埻 (low bleeding risk)烉⊭㊔ ≥ 80 mL/min 48⮷㗪ẍᶲ 48⮷㗪ẍᶲ ℏ夾掉↯䇯ˣ㓅嬟儢↯䇯ˣ⽫⮶䭉暣䓇䎮㩊 50–79 mL/min 72⮷㗪ẍᶲ 48⮷㗪ẍᶲ 㞍ㆾ䅺䀤ˣ⁛䴙埨䭉㓅⼙㩊㞍ˣ ⽫冇䭨⼳ 30–49 mL/min 96⮷㗪ẍᶲ 48⮷㗪ẍᶲ ☐墅伖䫱䫱ˤ㟡㒂僶≇傥ᶵ⎴炻 喍⺢嬘 15–29 mL/min ᶵ⺢嬘ἧ䓐 48⮷㗪ẍᶲ 㗪攻⤪堐15ˤ劍㚱⎰Ἕ䓐喍㚫⡆≈NOAC喍 < 15 mL/min ᶵ⺢嬘ἧ䓐 ᶵ⺢嬘ἧ䓐 䈑㽫⹎炻ἳ⤪烉amiodaroneˣdronedaroneˣ verapamil炻⇯⎗⺢嬘⣂ 喍24⮷㗪ˤ (d) ㇳ埻⼴ℵ㫉䓐⚆ NOAC䘬㗪攻烉Ỷ↢埨桐晒 (c) 檀↢埨桐晒䘬ㇳ埻 (high bleeding risk)烉⊭㊔ 䘬ㇳ埻㕤6-24⮷㗪⼴䃉两临↢埨⌛⎗㬋ⷠ㚵 墯暄⿏ℏ夾掉↯昌㱣䗪ˣ䠔兄⢾湣愱ˣ儘㢶 喍ˤ檀↢埨桐晒䘬ㇳ埻⇯䫱⇘48⮷㗪⼴攳⥳

165 ϛॳႱ٩ݽᕛࡾЕޱᡊᆰᠬଢ଼௉ܘᏗՖᏘҢܻЖתᏘο݈תŌࡼڼߨᆰт

㬋ⷠ㚵喍ˤ 2018 EHRA NOAC guideline⺢嬘ἧ䓐 dabigatran⍲apixaban䘬か侭炻劍ᶵ䡢⭂㗗⏎⶚ ⇘ᏗՖᏘϞ 㚵䓐忶喍䈑炻か侭ㅱ䫱⼭ᶳᶨ㫉⎫喍㗪攻תķįIJġġŏŐłńŴᇄ༈ಛο݈ ij ໢ޟᙽ඲ ℵ㬋ⷠ䓐喍ˤἧ䓐rivaroxaban␴edoxaban䘬か 2018 EHRA guideline⺢嬘⎒天INR < 2⯙⎗ 侭炻⇯㟡㒂か侭䘤䓇㞻⠆䘬桐晒炻桐晒檀䘬

ẍ䩳⌛⽆warfarin廱㎃䁢NOACs炻㭷ᶨNOAC⛐ (CHA2DS2VASc ≥ 3)⇯⺢嬘䩳⌛㚵䓐ᶨ∹炻桐晒

喍䈑廱㎃䘬䳘⇯䔍㚱ᶵ⎴炻ẍᶳ⍫侫⎬⭞ầ╖ Ỷ䘬(CHA2DS2VASc < 3)⇯⺢嬘䫱昼⣑䘬⎫喍㗪 ↿㕤ᶳ烉 攻ℵ㚵䓐喍䈑ˤ

ҢᒿᇲijٺķįijġŏŐłńŴҢ໔ ĸįġġϚ݂নӰϛॳЅᄇϛॳ௉ Dabigatran⍲apixabanᶨ⣑暨⎫2㫉炻か侭 ޱ୎กłŇġ ⭡㖻⾀姀炻ᶨ㖎⾀姀ℑᾳ∹慷(⏓)ẍᶲ炻⯙⭡ 㖻⡆≈㞻⠆䘬桐晒ˤ⎴㧋䘬炻rivaroxaban⍲ edoxaban⎒天⾀姀ᶨᾳ∹慷(⏓)ẍᶲ炻ḇ㚫⡆≈ ĸįIJġଲีܒłŇᇄϚ݂নӰϛॳᙏϭġ 㞻⠆䘬桐晒ˤ䁢性⃵か侭⾀姀⎫喍ˣㆾ㗗⾀姀 ⣏䲬㚱25%~30%䘬仢埨⿏ᷕ桐か侭ẍ⍲ ⶚䴻㚵䓐忶喍䈑侴忶慷ἧ䓐炻溻⊝か侭ἧ䓐枸 ⋲㔠䘬TIAか侭炻⌛ἧ䴻忶㧁㸾䘬姢㕟㩊㞍炻 ⃰↮墅⤥䘬喍䈑䙺炻⎗㷃⮹か侭ἧ䓐喍䈑䘬拗 ṵ䃞䃉㱽䡢娵ᷕ桐䘬⍇⚈炻⚈㬌㬠栆㕤ᶵ㖶 婌ˤ ⍇⚈ᷕ桐(cryptogenic stroke)139ˤ㚱ṃ䞼䨞栗 䣢炻忁ṃ㤝⎗傥冯ᶵ㖶Ἦ㸸䘬埨㞻(embolus of ķįijįIJġᒸᅓ݈᛾ unknown source)㚱斄炻忁栆か侭⛐2014⸜塓 劍拗忶㚵喍㗪攻炻㗗⏎天墄㚵拗忶䘬ᶨ∹ 㬠栆䁢ᶵ㖶Ἦ㸸䘬埨㞻✳ᷕ桐(embolic stroke 喍䈑烎2018 EHRA NOAC guideline⺢嬘劍怬⛐ of undetermined source, ESUS)ˤESUS䘬埨㞻 喍䈑㚵䓐攻昼䘬50%⋨攻ℏ炻⇯⎗ẍ墄㚵⾀姀 Ἦ㸸炻⊭㊔㛒䴻䘤䎦䘬昋䘤⿏AF (paroxysmal 䘬ᶨ∹喍䈑(ḇ⯙㗗婒dabigatran, apixaban拗忶 atrial fibrillation, PAF)炻℞Ṿ⍇⚈⊭⏓䒋兄䳸㥳 㚵喍㗪攻6⮷㗪ℏ炻rivaroxaban, edoxaban拗忶 ⓷柴炻ⶎ⽫⭌⓷柴炻䗴䕯䚠斄炻埨䭉㔹⟲(⊭ 㚵喍㗪攻12⮷㗪ℏ)ˤ崭忶Ḯ忁ᾳ㗪攻炻⇯ㅱ ⏓柠≽傰㔹⟲⍲ᷣ≽傰⺻㔹⟲)炻⍲Ἦ冒㕤攳 娚嶛忶⾀姀䘬忁ᶨ∹炻䫱ᶳᶨᾳ㚵䓐喍䈑㗪攻 㓦⿏⌝⚻⫼(patent foramen ovale, PFO)ㆾ℞Ṿ ⇘ℵ⎫喍ˤ⮵㕤㞻⠆檀桐晒ᶼ↢埨Ỷ桐晒䘬か ⽫㇧攻昼㥳忈䔘ⷠ忈ㆸ䘬⣯䔘㞻⠆(paradoxical 侭炻⎗ẍ侫ㄖ⺞攟墄䓐喍䈑䘬⭡姙㗪攻ˤ embolism)䫱⍇⚈140ˤPAF㗗ẍ攻㫯⿏㕡⺷↢ 䎦炻⣏⣂悥㗗㰺㚱⽝⃮䘬炻ᶨ凔ⷠ夷慓䗪ᶵ⭡ ķįijįijġ१ፒҢ᛾ 㖻㩊㞍↢PAF炻ḇ⮶农塓姢㕟㗪㨇⎗傥⺞怚炻 2018 EHRA NOAC guideline⺢嬘ἧ䓐 ẍ农檀桐晒か侭⺞婌㖑㛇ἧ䓐㈿ↅ埨∹ẍ枸旚 dabigatran⍲apixaban䘬か侭炻劍⾀姀⶚㚵䓐喍 ᷕ桐ㆾℐ幓⿏㞻⠆ḳẞ䘤䓇䘬㗪㨇141, 142ˤ ㇨ẍ 䈑侴ᶵ⮷⽫㚵䓐Ḯℑ᾵∹慷炻⇯嶛忶ᶳᶨ㫉 㖑㛇姢㕟AF㗗⼰慵天䘬ˤ䓙㕤㈨埻䘬∝㕘炻嬻 喍䈑㚵䓐炻ḇ⯙㗗24⮷㗪⼴ℵ㫉㚵喍ˤἧ䓐 ⽫埨䭉䮑㩊冯”㷔⎗ẍ㚜㶙ℍ᷎攟㛇䳗䧵炻㍸ rivaroxaban␴edoxaban䘬か侭炻⇯昼⣑䄏ⷠ㚵 檀Ḯ⮵㕤䃉䕯䉨PAF䘬䮑㩊㭼䌯ˤ㛔㔯㤪徘忁 喍ˤ ṃ䓐㕤攟㛇⽫埨䭉䚋㍏䘬㕘㈨埻炻ἧ䓐忁㈨埻 Ἦ㓡┬㔜橼AF㩊㷔㕡⺷炻᷎㍷徘忁ṃ㩊㷔㧉⺷ 姢㕟AF䘬慵天⿏ˤ ސķįijįĴġϚጂۡ࢐֏݈Ңႆ᛾

166 ϛॳႱ٩ݽᕛࡾЕޱᡊᆰᠬଢ଼௉ܘᏗՖᏘҢܻЖתᏘο݈תŌࡼڼߨᆰт

Пݲ 䡢娵か侭䘬冐⸲䕯䉨冯PAFᷳ攻䘬斄倗⿏ˤޟĸįijġҬࠉ୎กłŇ

ড়ۨܖҢłŇՖᔆॎӵຨ໢ٺĸįijįIJġ༈ಛ૕ຨПԒ ĸįijįĵġġ

䚖⇵炻”㷔AF㚨ⷠ䓐䘬㕡⺷㗗⛐慷埨⡻ ᑢᔮłŇ 䘬㗪῁炻䓐⁛䴙䘬ㇳ姢傰㎷Ἦ忚埴䮑㩊143, 144ˤ 劙⚳NICE (National Institute for Health Ữẍ㬌㕡㱽䮑㩊AF炻⚈檀⹎ẘ岜㩊㞍侭ᾳṢ䘬 and Care Excellence)䘬ˮ檀埨⡻姢㕟冯姽⭂˯ デ奢侴㚫㚱ῷⶖ炻㸾䡢⿏㚱℞旸⇞ˤᶨᾳ䲣䴙 (“Diagnosis and assessment of hypertension”) ᷕ ⊾⚆栏3ᾳ䞼䨞ℙ㚱2,385ỵか侭炻ἧ䓐傰姢Ἦ ⺢嬘⎗ἧ䓐WatchBP Home A埨⡻妰150ˤ娚埨⡻ 䮑㩊AF炻℞䮑㩊㩊↢䘬㓷デ⹎䁢94% (95% CI: 妰⛐慷埨⡻㗪炻⎗⎴㗪忚埴䮑㩊AFˤ憅⮵AF 84-97%)炻䈡䔘⿏㗗72% (95% CI: 69-75%)145ˤ ”㷔㸾䡢⿏䘬⸦ᾳ冐⸲䞼䨞炻⬫⮵AF”㷔䘬㓷 Hobbs䫱Ṣ⛐SAFE冐⸲䞼䨞(≥ 65㬚䘬か侭ℙ デ⹎忼97-100%炻䈡䔘⿏89-90%151, 152ˤ⮵ʁ65 4,933ỵ)炻㍉䓐傰姢Ἦ”㷔AF炻㓷デ⹎㗗87% 㬚ἧ䓐㬌㫦埨⡻妰忚埴㖍ⷠ埨⡻慷㷔炻℞䳸㝄 (95% CI: 82-91%)炻䈡䔘⿏㗗81% (95% CI: 80- 㭼崟ẍ⼨㍐啎䘬傰姢㕡⺷䮑㩊AF䁢Ἓ炻⮵㕤ᷕ 83%)146ˤὅ㒂ᶲ徘䘬䳸㝄炻思䄏慓⬠㊯⺽䘬慓 桐䘬枸旚᷎䭨䚩‍ᾅ剙屣㚱栗叿⸓≑150ˤ⛐ᶨ 䗪ⶍἄṢ⒉㍉䓐傰姢Ἦ AF䮑㩊ⶍ℟℞䈡䔘⿏ ᾳ➢Ⰼ㱣䗪╖ỵ⮵ʁ75㬚䘬1,000㮹䛦㇨ 䘬㭼 㭼庫ᶵ䎮゛147炻Ữ傰姢⌣㗗㚨㕡ὧ⍰ὧ⭄䘬AF 庫⮎槿炻ḇ嫱⮎娚埨⡻妰䘬檀䈡䔘⿏(90%)炻⎗ 䮑㩊ⶍ℟ˤ 㷃⮹廱ṳẍ⍲ℵἧ䓐12⮶䦳⽫暣⚾ 䮑㩊152ˤ Wiesel䫱Ṣ憅⮵139ἳ䘬か侭(℞ᷕ㚱14ỵ⶚䞍 ġġ ĸįijįij IJijᏲแЖႫყ 㚱AF)炻䞼䨞⯭⭞ἧ䓐WatchBP Home A埨⡻妰 12⮶䦳⽫暣⚾忂ⷠ塓⽫埨䭉⮰⭞娵⭂䁢” 䘬⎗埴⿏ˤ⎰妰ℙ3,316⣑ἧ䓐娚埨⡻妰䮑㩊⍲ 㷔AF䘬湫慹㧁㸾146ˤ晾䃞⿍⿏仢埨ᷕ桐か侭ḇ ⽫暣⚾䘬嬨ῤˤ冯event-trigger recorder䚠㭼炻 ⎗䓐12⮶䦳⽫暣⚾䚜㍍奨⮇⇘AF炻Ữ㰺奨⮇⇘ ⬫⮵AF”㷔䘬㓷デ⹎㗗99%炻䈡䔘⿏㗗93%ˤ AF炻䃉㱽㌺昌AFᶵ㗗忈ㆸ⿍⿏仢埨ᷕ桐䘬⍇ ℞ᷕ2ἳ⍇䃉AF䕭⎚炻䴻忶䮑㩊塓㩊㷔↢㚱 ⚈ˤ㒂Ộ妰ᷕ桐䘬か侭⣏䲬㚱30%䘬AF㗗攻㫯 PAF炻ἄ侭⺢嬘⯭⭞慷㷔埨⡻㗪⎗⎴㗪忚埴AF ⿏䘬148炻PAF䘬↢䎦塓╖㫉ㆾ暁慵䘬12⮶䦳⽫ 䮑㩊炻䃉䕯䉨䘬AF㚱⎗傥塓䮑㩊↢Ἦ153ˤ 暣⚾姀抬㨇㚫㗗⼰⮷䘬ˤ ĸįijįĶġසኋ࠮ऎᔜ၆ည୎กłŇIJĶĵġ

Ң೿៉ ㇳ僽䨧㇜ᷳ㘢ㄏ✳䨧㇜墅伖⇑䓐ٺߝਢ໢؁ܖĸįijįĴġġġġijĵωਢ ࠮ЖႫყᅿก photoplethysmography (PPG)”㷔⽖埨䭉䲣䴙ᷕ 忋临⿏䘬⽫暣⚾䚋㷔⊭⏓24⮷㗪⇘7⣑䘬 䘬埨慷嬲⊾炻᷎ẍ㬌妰䬿⽫嶛忇⹎ˤ2018⸜⹎ Holter炻event-recorder⍲external loop recorderˤ 䓙Teh䫱Ṣ憅⮵102ỵỷ昊か侭炻⎴㗪ἧ䓐忋临 Kirchhof䫱Ṣ⛐2007⸜䘤䎦Holterㆾevent- ⿏⽫暣⚾䚋㷔⍲䨧㇜FitBit (FB)⍲Apple watch recorder⎗ẍ⛐AFか侭⡆≈70%䘬姢㕟䌯ˤ侴 (AW) 30↮揀炻㭼庫FB⍲AW”㷔⽫⼳ᶵ㔜㗪 Holter”㷔㗪攻崲攟炻ᶵ婾㗗䕯䉨⿏ㆾ䃉䕯䉨 ⽫嶛忇⹎䘬㸾䡢⹎ˤ⮎槿䘤䎦⛐㬋ⷠ⽫⼳㕷佌 ⿏䘬AF塓䘤䎦䘬㨇䌯崲檀149ˤ侴external loop ᷕ炻ᶱ侭⽫嶛忇⹎⏣⎰⹎䚠䔞檀炻⛐⽫㇧⽫⼳ recorderᶨ凔墅伖䘬㗪攻䁢1-4忙炻⎗㟡㒂ℏ⺢ ᶵ㔜か侭炻AW冯⽫暣⚾⏣⎰⹎檀㕤FBˤ⽫㇧ 䘬”㷔⽫⼳ᶵ㔜䘬姢㕟㬍樇ㆾか侭冒䘤⿏┇≽ 㑚≽か侭炻FB⍲AW⽫嶛忇⹎⏣⎰⹎䘮冯⽫暣 ⮯㚱⓷柴㗪䘬⽫暣⚾姀抬ᶳἮ炻⚈㬌䚠䔞怑⎰ ⚾⸦役䚠⎴炻婌ⶖ䘮⮷㕤ᶨᾳ⽫嶛(1 beat)炻Ữ ᷣ≽⿏⻟惵⎰⹎檀䘬か侭ˤ⎴㗪ḇ⎗⋼≑慓ⷓ ⛐AFか侭FB⍲AW⽫嶛忇⹎”㷔䘮≋㕤⽫暣⚾

167 ϛॳႱ٩ݽᕛࡾЕޱᡊᆰᠬଢ଼௉ܘᏗՖᏘҢܻЖתᏘο݈תŌࡼڼߨᆰт

㇨”㷔ᷳ忇⹎(FB = -28 beats; AW = -8 beats)炻Ữ ⣂ᷕ⽫䘬䞼䨞163炻憅⮵1,135ỵ怬ᶵ䞍㗗⏎㚱AF 劍⽫嶛檀㕤100ᶳ/↮揀㗪炻㘢ㄏ✳䨧㇜墅伖㇨ 䘬朆䈡⭂⿏ᷕ桐ㆾTIAか侭炻忚埴72⮷㗪Holter ”㷔⇘䘬⽫嶛忇⹎炻98%䘬㔠ῤ冯ECG㇨”㷔 ECG䚋㍏炻49ỵ(4.3%)か侭塓”㷔↢㚱AFˤ29 䘬㔠ῤ句ⶖ䘮⛐10ᶳᷳℏˤ㘢ㄏ✳䨧㇜墅伖⛐ ỵ(2.6%)㗗⛐⇵24⮷㗪塓㩊㷔↢AF炻℞Ṿ20ỵ ”㷔㬋ⷠ⽫⼳⍲⽫㇧㑚≽䘬⽫嶛㔠㗪炻㚱ᶨ⭂ か侭㗗⛐⼴48⮷㗪塓”㷔↢AFˤ⎎ᶨ䭯䓙≈㊧ 䘬㸾䡢⹎烊Ữ㗗AF炻㘢ㄏ✳䨧㇜墅伖㇨”㷔䘬 ⣏䘬Sposato䞼䨞䘤䎦炻ᷕ桐⼴塓”㷔⇘䘬AF炻 ⽫嶛忇⹎⎗傥㚱ỶỘ䘬䉨㱩ˤ⚈㬌炻㘢ㄏ✳䨧 劍ᷕ桐⼴か侭㍍⍿㊩临⿏⽫冇䭨⼳徥希炻⸛ ㇜墅伖劍㚱”㷔⇘⽫㎷忶忇(⣏㕤100ᶳ/↮揀)䘬 ⛯䘤䎦か侭㚱AF䘬㗪攻䁢ᷕ桐⼴2⣑ℏ161烊侴 䉨㱩炻暨天⮷⽫㚱⽫㇧⽫⼳ᶵ㔜炻暨天㚜⮷⽫ Sposato⛐䴙⎰⿏䞼䨞ḇ䘤䎦炻ᷕ桐⼴AF㊩临䘬 䘬姽Ộか侭㗗⏎㚱㼃⛐䘬⽫⼳ᶵ㔜ˤ 㗪攻炻56.3%か侭㗪攻ᶵ崭忶30䥺164ˤ⚈㬌⛐ᷕ 桐⼴ḇ姙侫ㄖ㤝㖑㛇ᶼ㊩临⿏䘬䚋㷔炻庫傥䘤 ĸįijįķġġବᄇΙૡ௉ޱĩฒ੿ޑܖ୊ஶ 䎦㬌栆ᷕ桐⼴AF䘬↢䎦ˤ ҕಀĪġłŇᑢᔮ࡚ដ

ᅿกПԒġޟтڏ䃉䕯䉨AF⛐冐⸲ᶲ㗗ⷠ夳䘬䉨㱩ˤᶨ䲣䴙 ĸįĴįIJġ ⿏⚆栏䴙⎰30䭯忶⍣㔯䌣䘤䎦炻晐㨇䮑㩊AF⎗ ⃀䭉䞼䨞⶚䴻䡢娵ἧ䓐24ㆾ48⮷㗪⽫暣⚾ ㍸⋯65㬚ẍᶲか侭AF䚃埴䌯䓙䮑㩊⇵䘬2.3% 䚋㷔㚱℞⃒溆炻䃞侴忁ᾳ㕡㱽怬㗗ᶵ嵛㕤㩊㷔 ㍸⋯军4.4%炻侴℞ᷕ㚱67%か侭䘮䁢ᷕ桐檀桐 ↢㇨㚱℟㚱PAF䘬か侭ˤBang䫱Ṣ⛐ṾᾹ䘬姽 晒か侭炻ẋ堐忁ṃか侭⎗⚈䘤䎦AF炻㍸㖑ἧ䓐 婾ᷕ㍸⍲炻⇑䓐㓡列䘬㕘㈨埻ẍ⍲⮯䮑㩊㗪䦳 ㈿ↅ埨∹侴忼⇘枸旚ᷕ桐䘤䓇䘬㓰㝄155ˤ㫸㳚 ≈攟炻⮯⎗姢㕟↢㚜⣂℟㚱PAF䘬か侭165ˤ侴 ⽫冇⬠㚫㕤2017⸜㇨䘤堐䘬憅⮵AF䮑㩊䘬ℙ嬀 2014⸜䘬ℑᾳ慵天䘬冐⸲娎槿EMBRACE166 ⍲ 156炻⺢嬘65㬚ẍᶲか侭炻晐㨇ἧ䓐⁛䴙傰姢ㆾ CRYSTAL AF167 㓗㊩ẍᶲ䘬䘤䎦ˤ 㗗12⮶䦳⽫暣⚾㩊㷔㕡⺷䮑㩊AFˤ劍か侭䘬 EMBRACE䞼䨞栗䣢166炻30⣑䘬event-

CHA2DS2VASc↮㔠庫檀(≥ 2)炻攳⥳䮑㩊⸜䲨⎗ triggered recorder㭼⁛䴙24⮷㗪Holter ECG傥” 旵䁢55㬚ẍᶲˤ劍䁢75㬚ẍᶲか侭ㆾ䁢檀ᷕ桐 㷔㚜⣂AFˤ572ỵʁ55㬚℟⍇⚈ᶵ㖶䘬仢埨⿏ 桐晒か侭炻⇯⺢嬘㭷ỵか侭䘮㍍⍿12⮶䦳⽫暣 ᷕ桐ㆾTIAか侭炻䚠庫㕤24⮷㗪holtrer ECG炻 ⚾㩊㷔㕡⺷䮑㩊AFˤ event-triggered recording傥㚱㓰㍸⋯AF䘬”㷔 䌯 (㍸⋯5᾵)168ˤ⛐42ỵἧ䓐30⣑event-triggered ĸįĴġġϚ݂নӰϛॳܖෆԤϛॳ௉ޱ recorder”㷔㚱AFか侭炻⇵21ỵ㗗⛐䫔1忙⯙塓 łŇᑢᔮПԒ ”㷔↢炻℞检21ỵ㗗⛐⼴3忙㛇塓”㷔↢AFˤ 伶⚳⽫冇冯儎ᷕ桐⬠㚫⺢嬘炻⎗⮵⿍⿏仢 ⎎ᶨᾳẍ100ỵ仢埨⿏ᷕ桐侴䃉AF䕭⎚ 埨⿏ᷕ桐䘬か侭忚埴军⮹24⮷㗪ẍᶲ䘬⽫⼳䚋 䘬娎槿栗䣢炻⛐ᷕ桐⼴14⣑ℏ炻ẍstandard ㍏157ˤ䞼䨞嫱㖶炻⮵⶚か㚱仢埨⿏ᷕ桐ỷ昊㱣 practice (SP)㚱2%䘬か侭塓”㷔⇘AF炻侴㍍ 䗪䘬か侭炻㍉䓐24⮷㗪Holter ECG姀抬炻⎗ẍ ⍿SP⎰Ἕevent-recorder”㷔䘬か侭㚱18%塓䘤 柵⢾⡆≈5-16%姢㕟か侭⚈PAF侴⮶农仢埨⿏ 䎦㚱AF (P < 0.05)169ˤTayal䫱Ṣ㍉䓐⚆㹗⿏↮㜸 ᷕ桐ㆾTIA䘬㨇㚫158-161ˤFIND-AF䞼䨞⮵229ἳ ᷕ䘤䎦炻56ỵか侭ἧ䓐event-triggered recorder ⿍⿏仢埨⿏ᷕ桐か侭㍉䓐Holter ECG忚埴7⣑ 䚋㷔21⣑炻㈦↢Ḯ23%䘬ᶵ㖶⍇⚈ᷕ桐か侭℟ 䘬䚋㍏炻7⣑⼴䡢⭂13%℟㚱PAFˤ䴻忶48⮷㗪 㚱PAF炻䫔ᶨ㫉”㷔⇘AF䘬ᷕ攻㗪攻溆㗗7⣑ ⼴炻䲬⋲㔠PAF (n = 14)か侭塓”㷔↢Ἦ炻⎎ᶨ (䭬⚵2-19⣑)170ˤ ⋲㗗⛐48-168⮷㗪塓”㷔↢Ἦ162ˤ⎎ᶨᾳ⽟⚳ CRYSTAL-AF167 䲵ℍ441ỵẍ24⮷㗪⽫暣

168 ϛॳႱ٩ݽᕛࡾЕޱᡊᆰᠬଢ଼௉ܘᏗՖᏘҢܻЖתᏘο݈תŌࡼڼߨᆰт

⚾”㷔䃉AF䘬ᶵ㖶⍇⚈ᷕ桐か侭炻䚠庫㕤⁛ ĸįĵġԙҏਝઉ 䴙䘬䚋㷔㕡⺷炻攟㗪攻䘬㢵ℍ⺷⽫冇䚋㍏☐ (insertable cardiac monitor, ICM)”㷔↢庫⣂䘬 憅⮵ㆸ㛔㓰䙲↮㜸䘬䚠斄㔯䌣 䴙⎰↮ AF (6ᾳ㚰徥希炻19ỵ㭼3ỵ炻P < 0.001烊12ᾳ㚰 㜸䞼䨞䳸㝄栗䣢炻⮵⶚䘤䓇仢埨⿏ᷕ桐䘬攨姢 䘬徥希炻29ỵ㭼4ỵ炻P < 0.001)ˤ36ᾳ㚰徥希炻 か侭忚埴㊩临⿏⽫冇”㷔炻⎗柵⢾䘤䎦4.4% ICM䘬AF”㷔䌯忼30% (⁛䴙⺷䚋㍏䁢3%)171炻 か侭㚱AFㆾ㗗PAF炻忁㗗℟㚱㬋⎹ㆸ㛔㓰䙲 ẍICM”㷔⇘AF䘬⸛⛯㗪攻䁢ᷕ桐⼴8.4ᾳ㚰炻 䘬177ˤ`姕ẍか侭姢㕟↢AF᷎㍍⍿warfarin⍲ 81%䘬AF䁢䃉䕯䉨⿏䘬AFˤ䳸㝄栗䣢⁛䴙⺷䘬 beta-blockers䘬㱣䗪炻妰䬿㭷ᶨQALY (Quality 徥希䚋㍏⮵㕤”㷔AF㚱䚠䔞旸⇞ˤ Adjusted Life Year; QALY)ㆸ㛔⣏䲬䁢1.3叔伶 Ziegler䫱Ṣẍᶨᾳ⮷佌䳬↮㜸TRENDS ⃫炻Ỷ㕤㭷ᶨQALY 1.5叔伶⃫䘬攨㩣炻ὅ䄏伶 ⮎槿(ᶨ枭℟⇵䝣⿏䘬奨⮇⮎槿)炻ḇ嫱㖶ἧ ⚳ㆸ㛔㓰䙲䘬㧁㸾炻忁㗗℟㚱ㆸ㛔㓰䙲䘬ˤ㇨ 䓐ICM攟㛇姀抬䘬₡ῤ172ˤ⛐139ἳ℟㚱埨㞻 ẍ⽆ㆸ㛔㓰䙲䘬奨溆Ἦ婒炻⽭枰天㬋䡢姢㕟⍲ 㞻⠆ḳẞᷕ炻䴻忶1.1⸜䘬䚋㷔炻㚱45ỵか侭 㱣䗪AFㆾ PAF炻ㇵ㚱㚨Ἓ䘬QALYˤ (28%)䘤䎦㚱AFˤ⣏⣂㔠䘬か侭⛐⇵30⣑悥㰺 塓㩊㷔↢Ἦ炻堐䣢⎒㍉䓐30⣑䘬event-triggered ĸįĶġ๖ġᇭġ recorderἮ”㷔PAF㗗ᶵ⣈䘬173ˤ ⮵㕤ᶵ㖶⍇⚈䘬ᷕ桐か侭ἧ䓐24⮷㗪⽫ ῤ⼿㲐シ䘬㗗炻⛐CRYSTAL AF娎槿ᷕ炻 暣⚾䚋㷔ẍ姢㕟⽫⚈⿏埨㞻䘬⎗傥⶚㚱䞼䨞 ⮎槿䳬㚜㚱㓰䘬”㷔⇘AF炻か侭塓”㷔⇘AF Ỹ嫱ˤ䲬3-6%䘬か侭塓”㷔⇘㚱AF159, 160, 166ˤ 㗪ḇ㚱庫檀㭼ἳ廱㎃㱣䗪ㆸ㈿ↅ埨∹(14.7%㭼 EMBRACE䞼䨞嫱⮎30⣑䘬event-triggered 6.0%炻p = 0.007)炻⮎槿䳬ᷳᶨ⸜ℵᷕ桐桐晒 recorder㓡┬ḮAF䘬”㷔炻㭼崟ἧ䓐24⮷㗪 ḇ䔍Ỷ㕤⁛䴙䚋㷔㕡⺷䳬⇍(7.1%㭼9.1%)炻Ữ ⽫暣⚾炻⎗⼿⇘⣏㕤5᾵(⣏䲬16%)䘬㓰㝄166ˤ CRYSTAL AF娎槿᷎㰺㚱䈡⇍䴙妰ℑ䳬攻ℵᷕ ἧ䓐ICM军⮹30⣑ẍᶲ⎗忚ᶨ㬍⡆≈AF䘬” 桐桐晒㗗⏎㚱䴙妰⬠ᶲᷳⶖ䔘171ˤ 㷔炻ᶱ⸜䘬”㷔䌯㗗30%171ˤ2014⍲2018⸜伶 ⚳⽫冇冯ᷕ桐⬠㚫㱣䗪㊯⺽⺢嬘17, 178炻ˮ⮵㕤 㚦䴻㚱⿍⿏仢埨⿏ᷕ桐ㆾ㰺㚱℞Ṿ㖶栗⍇⚈䘬 ܒዖӵځĸįĴįijġġϚ݂নӰသϛॳӫ łŇޟႱกӰυ TIAか侭炻攟㛇⽫䌯䚋㷔(~30⣑)Ἦ”㷔AF㗗⎰ EMBRACE䞼䨞⺞Ỡ⛐24⮷㗪䘬⽫⼳䚋㷔 䎮䘬侫慷˯ˤỮ䨞䪇暨天 ⣂⭮普ㆾ⣂攟㗪攻 ᷕ䘤䎦炻⽫㇧㍸㖑㎷≽(atrial premature beats)䘬 䘬⽫䌯䚋㷔炻䚖⇵ṵ㛒㚱⭂婾ˤ 㔠慷冯㛒Ἦ䘤䎦㼃⛐⿏AF炻⊭⏓30⣑ˣ90⣑⍲ ⺢嬘烉 2⸜”㷔↢AF㚱䚜㍍斄Ὢ174ˤCRYSTAL AF䞼 (1) 12⮶䦳⽫暣⚾䁢”㷔AF䘬湫慹㧁㸾(Class 䨞ḇ䘤䎦炻⸜䲨⍲⺞攟䘬PR interval 㗗か侭⼴ I, Level of Evidence B)ˤ⣏㕤65㬚ˣㆾ 175 Ἦ塓䘤䎦㚱AF㚨ᷣ天䘬枸㷔⚈⫸ ˤ2018⸜䓙 CHA2DS2VASc↮㔠庫檀(≥ 2)䘬か侭侫ㄖ冒 Martini䫱Ṣ㇨ 䘬⚆栏⿏䞼䨞䘤䎦炻㭼庫222ỵ 55㬚ẍᶲ攳⥳炻⎗晐㨇ἧ䓐傰姢ㆾ㗗⽫暣⚾ ᶵ㖶⍇⚈ᷕ桐か侭ỷ昊㗪䘬⽫暣⚾⍲ỷ昊7⣑ℏ 䮑㩊AF (Class I炻Level of Evidence B)ˤỮ 䘬忋临⿏⽫暣⚾䚋㷔炻䘤䎦㚱P-wave dispersion ⸜䲨庫⣏㕷佌(⤪> 75㬚)ㆾAF伡か桐晒庫檀 ㆾ㗗ᶵ㬋ⷠ䘬P-wave axis㗗か侭⎗傥塓”㷔⇘ か侭(⤪ᷕ桐)炻ㅱ侫ㄖἧ䓐12⮶䦳⽫暣⚾ἄ 㚱㼃⛐⿏AF䘬⌙晒⚈⫸176ˤỮ⇘䚖⇵䁢㬊炻㬌 䁢䮑㩊ⶍ℟(Class IIa, Level of Evidence B)ˤ 栆䘬枸㷔⚈⫸⯂㛒㚱ᶨ⭂䘬⭂婾ˤ (2) ⮵ᷕ桐か侭炻䈡⇍㗗ᶵ㖶⍇⚈ᷕ桐か侭炻⎗ 侫ㄖ忚埴攟㛇⍲庫⭮普䘬⽫䌯䚋㷔炻⎗傥㚫

169 ϛॳႱ٩ݽᕛࡾЕޱᡊᆰᠬଢ଼௉ܘᏗՖᏘҢܻЖתᏘο݈תŌࡼڼߨᆰт

㚱㚜⣂䘬か侭塓㩊㷔↢AFˤ⽫䌯䚋㷔㗪攻 ⇯堐䣢喍䈑㽫⹎Ỷ⇘ᶵ℟㚱冐⸲シ佑ˤ侴 ⺢嬘军⮹24⮷㗪䓂军㚜攟(⤪72⮷㗪) (Class I, diluted thrombin time (dTT)冯ecarin chromogenic Level of Evidence B-NR)ˤᷕ桐か侭⎗侫ㄖ assay (ECA)⇯␴dabigatran䘬㽫⹎⏰䎦䚜㍍䶂⿏ ἧ䓐㚜攟㗪攻䘬⽫䌯䚋㷔炻⤪朆Ὕℍ⿏䘬⽫ 斄Ὢ炻㇨ẍ怑⎰䓐Ἦ⭂慷姽Ộdabigatran䘬㽫⹎ 䌯䚋㷔₨☐ㆾὝℍ⿏䘬⽫䌯䚋㷔₨☐炻ẍ㍸ 182ˤ䃞侴炻忁ṃ䈡㬲䘬ↅ埨㩊槿暨天塓娵嫱炻 檀AF”㷔(Class IIb, Level of Evidence B-R)ˤ 侴ᶼ屣㗪⍰ᶵ傥⺋㲃塓ἧ䓐炻⚈㬌㷃⮹Ḯ⛐䵲 Ữ䚖⇵⯂䃉䈡⭂㍐啎䘬”㷔㧉⺷⍲䫾䔍ˤ ⿍ね㱩ᶳ䘬䓐嗽ˤ 怠䓐怑⎰䘬㩊槿㕡⺷⎗ẍ䓐Ἦ姽Ộ⎬ ߣᓃŏŐłńޟᔮก 䧖NOAC䘬埨㻧㽫⹎炻晾䃞冐⸲娎槿ᷕ㗗䓐 ⷠ夷ↅ埨㩊槿(PT␴aPTT)䃉㱽㸾䡢姽Ộ 㵚䚠Ⰼ㜸岒嬄₨(HPLC/MS)Ἦ㷔慷㽫⹎炻Ữ NOAC䘬㈿ↅ埨㓰㝄炻Ữ⎗ẍ德忶䈡㬲䘬ↅ埨 ⎗ẍ㤪䔍䓐㟉㸾忶䘬dTT/ECA assayἮ䚋㷔 㩊槿Ἦ⭂慷NOAC埨㻧喍䈑㽫⹎炻忚侴姽Ộ dabigatran炻ㆾ䓐chromogenic anti-FXa assayἮ NOAC䘬㈿ↅ埨㓰㝄179-181ˤ⣏⣂㔠䘬埨ↅ⹎㷔 䚋㷔FXa inhibitors䘬喍䈑㽫⹎ˤ⺢嬘ᷣ天ἧ 慷₨(coagulometers)⎗⛐30↮揀ℏ㷔慷↢NOAC 䓐埨㻧㽫⹎侴ᶵ㗗anti-Xa activityㆾdTTἮ 埨㻧喍䈑㽫⹎炻⚈㬌慓䗪昊㇨⎗ẍ侫ㄖℐ⣑ NOAC㽫⹎䘬⭂慷姽Ộˤ堐17栗䣢㚵䓐NOAC ῁㍸ὃ忁ṃ㩊槿Ἦ䓐㕤䵲⿍ね㱩182ˤ⍵ᷳ炻䚖 ⼴枸㛇䘬喍䈑㲊Ⲙ␴㲊察㽫⹎182ˤ⇌嬨㚵䓐 ⇵⯂㛒⮵㚵䓐NOAC䘬か侭㍸ὃ⭂溆䄏嬟㩊槿 NOACか侭䘬ↅ埨娎槿䳸㝄㗪炻䞍忻㚵喍㗪攻 (point-of-care tests)183ˤ ␴㉥埨㗪攻嶅暊⣂ᷭ㗗⼰慵天䘬ˤNOAC⮵ↅ ⏰刚↮㜸㱽(anti-FXa chromogenic assays)⎗ 埨娎槿䘬㚨⣏⼙枧㚫↢䎦⛐埨㻧㽫⹎㚨檀㗪炻 䓐Ἦ㷔慷䫔⋩⚈⫸㈹⇞∹(FXa inhibitors)䘬埨㻧 ⣏䲬⛐㚵䓐喍䈑2-3⮷㗪⼴179ˤ 㽫⹎炻⤪㝄㷔慷䳸㝄栗䣢䃉anti-FXa activity炻 Dabigatran

堐17ˢか侭㚵䓐NOAC䘬埨㻧喍䈑㽫⹎␴ↅ埨娎槿

Dabigatran Rivaroxaban Apixaban Edoxaban 㱣䗪AFか侭䘬枸㛇NOACs埨㻧㽫⹎ (dabigatran㟡㒂dTT/ECA侴Xa inhibitors㟡㒂anti-FXa activity) ⛐㧁㸾∹慷ᶳ枸㛇䘬㲊Ⲙ埨㻧㽫 64-443 184-343 69-321 91-321 ⹎(ng/mL) ⛐㧁㸾∹慷ᶳ枸㛇䘬㲊察埨㻧㽫 31-225 12-137 34-230 31-230 ⹎(ng/mL) NOACs⮵ⷠ夷ↅ埨娎槿䘬枸㛇⼙枧 PT ɥɥɥ(ɥ)(ɥ) ɥ(ɥ) aPTT ɥɥ(ɥ) ɥ (ɥ) ɥ ACT ɥ(ɥ) ɥɥɥ TT ɥɥɥɥ ––– ⁁姣: 娎∹㚫⼙枧 PT⮵FXa inhibitors⍲aPTT⮵dabigatran䘬㓷デ⹎炻䔞怠䓐㓷デ䘬㩊槿㗪炻㬋ⷠ 䘬aPTT⎗㌺昌dabigatran崭忶䗪㓰㽫⹎炻㬋ⷠ䘬PT⎗㌺昌rivaroxaban␴edoxaban崭忶䗪㓰㽫 ⹎炻Ữ䃉㱽䓐⛐ἧ䓐apixaban㱣䗪䘬か侭ˤ⭂溆䄏嬟㩊槿㇨ἧ䓐䘬INR㷔慷₨☐⎗䓐Ἦ䚋㷔 warfarinỮ䃉㱽㸾䡢姽Ộ㚵䓐NOACか侭䘬㈿ↅ埨䉨ンˤ ACT, activated clotting time; aPTT, activated partial thromboplastin time; dTT, diluted thrombin time; ECA, ecarin clotting assay; INR, international normalized ratio; PT, prothrombin time.

170 ϛॳႱ٩ݽᕛࡾЕޱᡊᆰᠬଢ଼௉ܘᏗՖᏘҢܻЖתᏘο݈תŌࡼڼߨᆰт

PTT⎗㍸ὃdabigatran喍䈑㽫⹎␴㈿ↅ埨 College of Cardiology/American Heart ἄ䓐䘬⭂⿏姽ỘˤDabigatran␴aPTT⏰㚚䶂䚠 Association Task Force on Clinical Practice 斄184炻㬋ⷠ䘬aPTT䃉㱽㌺昌dabigatran㽫⹎⛐ Guidelines and the Heart Rhythm Society in 䗪㓰䭬⚵䘬⎗傥⿏炻Ữ⎗ẍ㌺昌崭忶䗪㓰㽫 Collaboration With the Society of Thoracic ⹎䘬⎗傥⿏ˤDabigatran⛐㬋ⷠ䗪㓰㽫⹎⮵PT Surgeons. Circulation 2019;140:e125-e151. ␴INR⼙枧ᶵ⣏炻㇨ẍ忁ṃ㩊㞍ᶵ怑⎰䓐Ἦ姽 2. Steffel J, Verhamme P, Potpara TS, et al. The Ộdabigatran䘬㈿ↅ埨ἄ䓐183ˤThrombin time 2018 European Heart Rhythm Association (TT) ⮵dabigatran⼰㓷デ炻⌛ἧ⼰Ỷ㽫⹎䘬 Practical Guide on the use of non-vitamin K dabigatranḇ㚫ἧTT⺞攟炻㇨ẍ㬋ⷠ䘬TT⎗ẍ antagonist oral anticoagulants in patients with ㌺昌dabigatran䘬喍㓰⬀⛐ˤTTᶵ怑⎰䓐Ἦ⭂慷 atrial fibrillation. Eur Heart J 2018;39:1330- 姽Ộ⛐冐⸲䗪㓰㽫⹎䭬⚵ℏ䘬dabigatran炻䚠⍵ 1393. ⛘炻dTT␴ECA⎗䓐Ἦ姽Ộ⛐冐⸲䗪㓰㽫⹎䭬 3. Lip GYH, Banerjee A, Boriani G, et al. ⚵ℏ䘬dabigatran182ˤ Antithrombotic Therapy for Atrial Fibrillation: 䫔⋩⚈⫸㈹⇞∹Factor Xa inhibitors (rivaroxaban, CHEST Guideline and Expert Panel Report. apixaban, and edoxaban) Chest 2018;154:1121-1201. ᶵ⎴䘬䫔⋩⚈⫸㈹⇞∹⮵PT␴aPTT䘬⼙枧 4. Diener HC, Aisenberg J, Ansell J, et al. 䦳⹎ᶵᶨ㧋炻aPTT䃉㱽䓐Ἦ㚱シ佑⛘姽ỘFXa Choosing a particular oral anticoagulant 䘬㈹⇞㓰㝄ˤ晾䃞䫔⋩⚈⫸㈹⇞∹䘬㽫⹎␴PT and dose for stroke prevention in individual 䘬⺞攟䚠斄炻Ữ⼙枧䦳⹎㚫␴㷔慷㕡㱽⍲ᶵ⎴ patients with non-valvular atrial fibrillation: 䫔⋩⚈⫸㈹⇞∹㚱斄ˤ㬌⢾炻PTᶵ℟㚱⮰ᶨ part 2. Eur Heart J 2017;38:860-868. ⿏炻㚫⍿℞Ṿ⚈䳈⼙枧(ἳ⤪偅≇傥㎵ ㆾ䵕Ṿ 5. Kirchhof P, Benussi S, Kotecha D, et al. 2016 ␥K仢᷷)185ˤ⮵apixabanἮ婒炻PT䃉㱽䓐Ἦ姽 ESC Guidelines for the management of atrial Ộ℞㈿ↅ埨㓰㝄ˤ侴⮵rivaroxaban⍲edoxaban fibrillation developed in collaboration with (庫⮹䦳⹎ᶲ)Ἦ婒炻PTㆾ姙傥㍸ὃᶨṃ⭂慷姽 EACTS. Europace 2016;18: 1609-1678. Ộ炻Ữ㓷デ⿏⍾㰢㕤㇨怠㑯䘬娎∹180炻⚈㬌⻟ 6. Killu AM, Granger CB, Gersh BJ, et al. Risk 䁰⺢嬘天⃰姽Ộ㇨ἧ䓐䘬PT娎∹⮵㕤䫔⋩⚈⫸ stratification for stroke in atrial fibrillation: a ㈹⇞∹䘬㓷デ⹎ˤ慵天䘬㗗炻⮯PT廱㎃䁢INR critique. Eur Heart J 2019;40:1294-1302. ⍵侴⡆≈Ḯ嬲䔘⿏炻INR䃉㱽⎗月⛘姽Ộ䫔⋩ 7. National Heart Foundation of Australia and ⚈⫸㈹⇞∹䘬㓰㝄ˤ䔞天⮯NOAC㎃ㆸἧ䓐 the Cardiac Society of Australia and New warfarin㗪炻NOAC忈ㆸ䘬PT/INR⺞攟⎗傥㚫忈 Zealand: Australian Clinical Guidelines for ㆸ婌⮶炻㇨ẍ廱㎃喍䈑㗪暨天⮷⽫⛘➟埴ˤ the Diagnosis and Management of Atrial Fibrillation 2018. Heart Lung Circ 2018;27: ୤ՃМᝦ 1209-1266. 8. Chao TF, Liu CJ, Wang KL, et al. Using the 1. January CT, Wann SL, Calkins H, et al. CHA2DS2-VASc score for refining stroke 2019 AHA/ACC/HRS Focused Update of risk stratification in 'low-risk' Asian patients the 2014 AHA/ACC/HRS Guideline for with atrial fibrillation. J Am Coll Cardiol the Management of Patients With Atrial 2014;64:1658-1665. Fibrillation: A Report of the American 9. Chiang CE, Wu TJ, Ueng KC, et al. 2016

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Assessment of the impact of rivaroxaban summary. Europace 2018;20:1231-1242. on coagulation assays: laboratory 183. van Ryn J, Baruch L, Clemens A. recommendations for the monitoring of Interpretation of point-of-care INR results in rivaroxaban and review of the literature. patients treated with dabigatran. Am J Med Thromb Res 2012;130:956-966. 2012;125:417-420. 181. Douxfils J, Mullier F, Robert S, et al. Impact 184. van Ryn J, Stangier J, Haertter S, et al. of dabigatran on a large panel of routine Dabigatran etexilate--a novel, reversible, or specific coagulation assays. Laboratory oral direct thrombin inhibitor: interpretation recommendations for monitoring of dabigatran of coagulation assays and reversal of etexilate. Thromb Haemost 2012;107:985- anticoagulant activity. Thromb Haemost 997. 2010;103:1116-1127. 182. Steffel J, Verhamme P, Potpara TS, et al. The 185. Lindhoff-Last E, Samama MM, Ortel TL, et 2018 European Heart Rhythm Association al. Assays for measuring rivaroxaban: their Practical Guide on the use of non- Mullier suitability and limitations. Ther Drug Monit F,vitamin K antagonist oral anticoagulants 2010;32:673-679. in patients with atrial fibrillation: executive

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2019 Taiwan Stroke Society Guideline on the Use of Non- Vitamin K Antagonist Oral Anticoagulants for Prevention of Stroke in Patients with Atrial Fibrillation

Ya-Ju Lin1, Ying-Ting Huang1, Pai-Ching Tsui1, Li-Kai Tsai2, Chih-Ping Chung3, Shu-Fan Kuo1, Pi-Shan Sung4, Helen L. Po1, 5, Taiwan Stroke Society Guideline Consensus Group

1Department of Neurology, MacKay Memorial Hospital, Taipei, Taiwan. 2Department of Neurology, National Taiwan University Hospital, Taipei, Taiwan. 3Department of Neurology, Neurological Institute, Taipei Veterans General Hospital, Taipei, Taiwan. 4Department of Neurology, National Cheng Kung University Hospital, Tainan, Taiwan. 5Stroke Center, MacKay Memorial Hospital, Taipei, Taiwan.

ABSTRACT

Between 2011 and 2016, four non-vitamin K antagonist oral anticoagulants (NOACs), dabigatran (a direct thrombin inhibitor), rivaroxaban, apixaban, and edoxaban (direct factor Xa inhibitors) were approved by Taiwan Food and Drug Administration (TFDA) for stroke prevention in atrial fibrillation (AF). The introduction of NOACs has changed the approach of stroke prevention in patients with AF and have emerged as the preferred choice especially in patients newly started on anticoagulation. Increased use of NOACs is a result of improved efficacy and safety, predictable anticoagulant effect without need for routine coagulation monitoring, simplified regimens, and fewer food and drug interactions compared with warfarin. The purpose of this current guideline is to update the 2012 and 2016 Taiwan Stroke Society (TSS) Guideline particularly in areas for which new evidence has emerged since its publication. The TSS Guideline Consensus Group revised the guideline based on the data of the Taiwanese and Asian populations and the recent guidelines of the European Heart Rhythm Association, American Heart Association, American College of Chest Physician and Asia Pacific Heart Rhythm Society. This guideline deals with the definition of nonvalvular AF (NVAF), the use of NOACs in patients with acute ischemic stroke (AIS), the management of bleeding under NOACs, how to deal with NOACs in specific clinical situations, how to deal with dosing errors, when to stop NOACs when undergoing a planned invasive procedure or surgery, and screening for AF.

Keywords: atrial fibrillation, stroke prevention, non-vitamin K antagonist oral anticoagulants

Corresponding author: Dr. HL Po, Stroke Center, MacKay Memorial Hospital, Taipei, Taiwan. E-mail: [email protected]

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IJįġࠉȁȁِ 㞻喍䈑䘬䉨㱩ᶳ炻ICH䘬埨⟲㒜⣏䌯䲬䁢30%- 40%3炻侴劍㍍⍿㈿ↅ埨∹㱣䗪炻⇯㚫⡆≈军 ㈿ↅ埨∹䚠斄⿏儎↢埨䁢忈ㆸ冒䘤⿏儎 36%-54%9-11炻⚈㬌炻⍵廱㈿ↅ埨∹䘬㓰㝄炻ἧ ℏ↢埨(intracerebral hemorrhage, ICH)䘬ᷣ天⍇ 埨㵚《⽑ↅ埨≇傥䁢㱣䗪㈿ↅ埨∹䚠斄⿏儎↢ ⚈ᷳᶨ炻⛐忶⍣㫸伶⚳⭞䘬䴙妰ᷕ炻檀忼14% 埨䘬ᶨ枭慵溆冯䌐䈡ᷳ嗽3, 12ˤ䚖⇵⍵廱㈿ↅ埨 䘬冒䘤⿏ICH␴喍䈑ἧ䓐䚠斄1炻⛐⎘䀋⇯㚱 ἄ䓐䘬喍䈑⎗↮䁢ℑ䧖炻ᶨ䧖䁢憅⮵䈡⭂㈿ↅ 䲬2.6%䘬冒䘤⿏ICH㸸㕤㈿ↅ埨∹2ˤ㈿ↅ埨 埨∹䳸⎰ẍ㈹⇞℞ἄ䓐䘬⍵廱∹炻侴⎎ᶨ䧖䁢 ∹䘬䧖栆䚠䔞⣂⃫炻℞ἄ䓐㨇廱ᷣ天䁢啱䓙⼙ ⏓㚱ↅ埨⚈⫸䘬埨㵚墥⑩炻啱䓙䚜㍍墄⃭ↅ埨 枧橼ℏↅ埨⚈⫸䘬忳ἄ侴ἧ埨㵚暋ẍↅ⚢ˤ⎋ ⚈⫸ẍ⚆⽑ↅ埨≇傥7ˤ昌Ḯ暨⍵廱㈿ↅ埨∹䘬 㚵✳㈿ↅ埨∹⊭㊔䵕䓇䳈K㊖㈿∹(vitamin K 㓰㝄⢾炻㈿ↅ埨∹䚠斄⿏儎↢埨䘬㱣䗪㕡⺷冯 antagonist)炻␴朆䵕䓇䳈K㊖㈿∹✳⎋㚵㈿ↅ埨 ᶨ凔冒䘤⿏ICH䘬嗽䎮⣏农䚠⎴炻⊭㊔埨⡻㍏ ∹(non-vitamin K antagonist oral anticoagulant, ⇞ˣ⢾䥹ㇳ埻ẍ䦣昌埨⟲ㆾ侭㷃Ỷ儎⡻炻ẍ⍲ NOAC)ℑ䧖炻㚨ⷠ塓ἧ䓐䘬䵕䓇䳈K㊖㈿∹䁢 枸旚Ἕ䘤䕯䫱12ˤ㬌䭯㔯䪈㔜䎮Ḯ忶⍣㔯䌣炻 warfarin炻䞼䨞栗䣢炻ἧ䓐warfarin䘬か侭炻㭷 ⮯叿慵㕤妶婾ᶵ⎴㈿ↅ埨∹䘬⍵廱喍䈑⍲℞ἧ ⸜䲬㚱0.3%军1.1%䘬㨇㚫䘤䓇ICH3炻侴NOAC 䓐㕤㈿ↅ埨∹䚠斄⿏儎↢埨ᷕ䘬㓰㝄ˤ 䘬ICH桐晒䲬䁢warfarin䘬ᶨ⋲4炻㬌ⶖ䔘⛐Ṇ㳚 ᏘĩŷŪŵŢŮŪůġŌġת㕷佌⯌䁢㖶栗5ˤ憅∹✳㈿ↅ埨∹⊭㊔⁛䴙✳偅 ijįġġᆰҡશŌࡼ 䳈(unfractionated heparin)ˣỶ↮⫸慷偅䳈(low ŢůŵŢŨŰůŪŴŵĪ molecular weight heparin)␴⎰ㆸḼ䡛䱾(synthetic pentasaccharide)䫱炻忶⍣⛐⽫倴㠿⠆䘬䞼䨞㊯ 䵕䓇䳈K㊖㈿∹啱䓙㈹⇞䵕䓇䳈K䚠斄䘬 ↢炻ἧ䓐偅䳈䘬か侭炻℞栙ℏ↢埨㭼䌯䲬䁢 ↅ埨⚈⫸(ↅ埨⚈⫸IIˣVIIˣIXˣX)忼⇘㈿ↅ 0.7%6炻侴⛐仢埨⿏儎ᷕ桐䘬䕭Ṣᷕ炻⇯⎗檀忼 埨ἄ䓐炻℞ᷕ㚨䁢⺋㲃ἧ䓐侭䁢warfarin13ˤ 2.7%7ˤ 冐⸲ᶲ炻忂ⷠẍ⚳晃㧁㸾⊾㭼ῤ(international ㈿ↅ埨∹䚠斄⿏儎↢埨䁢冒䘤⿏ICH䔞ᷕ normalized ratio, INR)㔠ῤἮ䚋㷔䵕䓇䳈K㊖ 枸⼴㚨䁢♜慵䘬ᶨ䧖炻℞ᶨ⸜㬣ṉ䌯⎗檀忼 ㈿∹䘬㓰㝄炻᷎ 䁢喍䈑婧㔜䘬ὅ㒂7炻忶⍣ 40%-60%2, 3炻⎒㚱ᶵ⇘Ḵㆸ䘬䕭Ṣ⛐3ᾳ㚰㗪 warfarin䚠斄ICH䘬䞼䨞栗䣢炻⍵廱㈿ↅ埨ἄ䓐 傥䌐䩳埴崘8烊䞼䨞Ṏ栗䣢炻⛐㰺㚱ἧ䓐㈿埨 ⎗旵Ỷ埨⟲㒜⣏䌯⍲㬣ṉ䌯14炻⚈㬌炻⛐㬌栆

忂妲ἄ侭烉哉≃↙慓ⷓ ⎘⣏慓昊䤆䴻悐㙐儎ᷕ桐ᷕ⽫ E-mail: [email protected] DOI: 10.6318/FJS.201912_1(3).0002

185 ݽᕛސ᛾ޟသюՖܒᏗՖᏘࣺᜰת

䕭Ṣᷕ炻ㅱ⃀㖑⚆⽑℞ↅ埨≇傥15ˤ < 2㗪炻㗗⏎庫Ỷ∹慷䘬ↅ埨愞墯⎰㽫䷖䈑ὧ 䵕䓇䳈K䁢䵕䓇䳈K㊖㈿∹䘬⍵廱∹炻⬫ 嵛ẍ⍵廱䵕䓇䳈K㊖㈿∹䘬㈿ↅ埨㓰㝄炻ᶨᾳ ᶵỮ℟㚱⚆⽑㈿ↅ埨䘬㓰㝄炻ᶼ㬌㓰㝄℟㚱㊩ 䞼䨞㓞⍾Ḯ䵕䓇䳈K㊖㈿∹䚠斄⿏栙ℏ↢埨ᶼ 临⿏3, 13炻䃞侴䵕䓇䳈K䘬ἄ䓐崟⥳㗪攻庫攟炻 INR < 2䘬か侭炻栗䣢忁ṃか侭ἧ䓐庫Ỷ∹慷 ⛐䴎Ḱ喍䈑⼴2⮷㗪ㇵ㚫攳⥳ἄ䓐炻12军24⮷ 䘬ↅ埨愞墯⎰㽫䷖䈑⎴㧋⎗䞗㬋ↅ埨≇傥19炻 㗪⼴ㇵ忼㚨⣏䗪㓰3, 12炻⚈㬌炻䁢Ḯ⃀㖑⚆⽑ ⚈㬌MMC guideline⺢嬘炻䔞INRῤ䁢1.6-1.9ˣ ↅ埨≇傥炻⼨⼨暨天㏕惵ↅ埨愞墯⎰㽫䷖䈑 2-3.9ˣ4-5.9炻⍲≥ 6㗪炻↮⇍䴎Ḱか侭㭷℔㕌 (prothrombin complex concentrate, PCC)ἧ䓐3, 7, 15ˣ25ˣ35␴50╖ỵ䘬ↅ埨愞墯⎰㽫䷖䈑炻䔞 13ˤↅ埨愞墯⎰㽫䷖䈑㚱ℑ䧖⼊⺷炻ᶱ⚈⫸ↅ 橼慵崭忶100℔㕌㗪炻ẍ100℔㕌妰19ˤ㛒Ἦ炻 埨愞墯⎰㽫䷖䈑⊭⏓ↅ埨⚈⫸IIˣIX␴X炻侴 怬㚱⼭㚜⣂䞼䨞ẍ㞍嫱炻ỽ媪㱣䗪䵕䓇䳈K㊖ ⚃⚈⫸ↅ埨愞墯⎰㽫䷖䈑⇯⣂Ḯↅ埨⚈⫸VIIˣ ㈿∹䚠斄ICH炻㚨怑䔞䘬ↅ埨愞墯⎰㽫䷖䈑ἧ 噳䘥C (protein C)␴噳䘥S (protein S)䫱13ˤ忶⍣ 䓐∹慷ˤ warfarin䚠斄⿏儎↢埨䘬䞼䨞栗䣢炻冯㕘歖⅟ⅵ ䷥㊔侴妨炻䔞忯⇘䵕䓇䳈K㊖㈿∹䚠斄ICH 埨㻧(fresh frozen plasma, FFP)䚠㭼炻ἧ䓐⚃⚈ 㗪炻ㅱ䩳⌛ 㬊䵕䓇䳈K㊖㈿∹䘬ἧ䓐炻᷎ẍ ⫸ↅ埨愞墯⎰㽫䷖䈑傥㚜彭忇⛘䞗㬋INRῤ炻 朄傰㲐⮬䘬㕡⺷炻䴎Ḱか侭10㮓⃳䘬䵕䓇䳈K ᶼ␴庫Ỷ䘬埨⟲㒜⣏䌯⍲庫⤥䘬枸⼴䚠斄3, 13, ␴㭷℔㕌25-50╖ỵ䘬⚃⚈⫸ↅ埨愞墯⎰㽫䷖䈑 16ˤ⛐∗ἄ䓐㕡朊炻ἧ䓐⚃⚈⫸ↅ埨愞墯⎰㽫 ẍ⍵廱㈿ↅ埨ἄ䓐3, 15ˤ⛐ↅ埨愞墯⎰㽫䷖䈑䴎 ䷖䈑␴㕘歖⅟ⅵ埨㻧䘮㚱3%-8%䘤䓇埨䭉㞻⠆ Ḱ⼴15军60↮ℏ徥希INR15炻㬌⼴ㅱ㭷6-8⮷㗪 ḳẞ䘬㨇㚫13炻䃞侴炻㕘歖⅟ⅵ埨㻧㚱庫檀䘬 䚋㷔INRẍ姽Ộ㱣䗪㓰㝄炻劍INR㰺㚱⛐24-48 忶㓷冯橼㵚忶⣂䘬桐晒3ˤ ⮷㗪ℏ忼⇘䚖㧁ῤ炻⎗ℵ䴎Ḱ䫔Ḵ∹䵕䓇䳈K 忶⍣炻⣂㔠ẍↅ埨愞墯⎰㽫䷖䈑⍵廱䵕 (⎴㧋䁢朄傰㲐⮬10㮓⃳)⍲㕘歖⅟ⅵ埨㻧13ˤ侴 䓇䳈K㊖㈿∹㈿ↅ埨㓰㝄䘬䞼䨞炻⛐ἧ䓐ↅ埨 ⛐䃉㱽⍾⼿ↅ埨愞墯⎰㽫䷖䈑䘬䉨㱩ᶳ炻ㅱẍ 愞墯⎰㽫䷖䈑㗪炻㚫ὅ㒂か侭䘬橼慵䴎Ḱ㭷℔ 朄傰㲐⮬10㮓⃳䵕䓇䳈K⎰Ἕ㭷℔㕌10-15㮓⋯ 㕌25-50╖ỵ䘬∹慷炻㚱㗪㚫ℵὅ㒂INRῤ 䘬㕘歖⅟ⅵ埨㻧㚧ẋᷳ13 (堐1)ˤ 婧㔜炻䃞侴炻㚨怑䔞䘬ἧ䓐∹慷䚖⇵ṵᶵ㖶 Ꮨ࠮ο݈ת䡢15-22ˤ⛐2015⸜㗪炻ἧ䓐ↅ埨愞墯⎰㽫䷖䈑 ĴįġġߨᆰҡશŌࡼ ᏗՖᏘĩŏŐłńĪת ⍵廱䵕䓇䳈K㊖㈿∹䘬䫔ᶱ㛇冐⸲娎槿㊯↢炻 ↅ埨愞墯⎰㽫䷖䈑忼⇘㬊埨䘬㓰㝄庫埨㻧⃒ 䔘炻⛐㬌娎槿ᷕ炻ↅ埨愞墯⎰㽫䷖䈑䘬ἧ䓐∹ NOAC⎗ὅ㒂ἄ䓐㨇廱↮䁢䚜㍍ↅ埨愞㈹ 慷炻ὅ㒂INRῤ侴㚱㇨ᶵ⎴炻㬌娎槿⛐INR䁢 ⇞∹(direct thrombin inhibitor)⍲䫔⋩⚈⫸㈹⇞∹

2-4ˣ4-6炻⍲> 6㗪炻↮⇍䴎Ḱか侭㭷℔㕌25ˣ (factor Xa inhibitor)ℑ䧖ˤDabigatran䁢ᶨᷣ天䴻 17 35␴50╖ỵ䘬∹慷 ˤᶨ䭯䘤堐㕤2016⸜Lancet 䓙僶冇㌺↢䘬⎗微✳䚜㍍ↅ埨愞㈹⇞∹炻℞喍 Neurology炻憅⮵䵕䓇䳈K㊖㈿∹䚠斄ICH䘬冐 䈑⋲堘㛇⛐僶冇≇傥㬋ⷠ䘬か侭ᷕ炻䲬䁢12-17 ⸲娎槿⇯㊯↢炻ↅ埨愞墯⎰㽫䷖䈑⍵廱㈿ↅ埨 ⮷㗪炻侴⛐僶冇≇傥䔘ⷠ䘬か侭ᷕ炻⇯⎗⺞攟 䘬傥≃栗叿⛘⃒㕤㕘歖⅟ⅵ埨㻧炻᷎⎗傥冯庫 军15-34⮷㗪15ˤ晾䃞冯䵕䓇䳈K㊖㈿∹䚠庫侴 ⮷䘬↢埨慷䚠斄炻⛐㬌娎槿ᷕ炻ↅ埨愞墯⎰ 妨炻NOAC庫⮹冯℞⬫喍䈑䓊䓇ṌḺἄ䓐炻䃞 16 㽫䷖䈑䘬ἧ䓐∹慷䁢㭷℔㕌30╖ỵ 烊䃞侴炻 侴㝸ṃ喍䈑炻⤪P態噳䘥㈹⇞∹(P-glycoprotein

ᶲ徘ℑ䭯䞼䨞㇨㓞⍾䘬か侭炻⇅⥳䘬INRῤ䘮 inhibitors)ṵ⎗傥⡆≈dabigatran䘬⏠㓞侴ἧ℞㈿

≥ 2炻⚈㬌役㛇⎎㚱ᶨṃ⬠侭▿娎㍊妶炻䔞INR ↅ埨㓰㝄⡆≈15ˤ

186 ݽᕛސ᛾ޟသюՖܒᏗՖᏘࣺᜰת

Idarucizumab䁢憅⮵dabigatran㇨姕妰䘬⍵ ↢炻andexanet alfa⎗㕤5↮揀ℏ旵Ỷrivaroxaban 廱∹炻䁢ᶨ⎗䳸⎰军dabigatran䘬ↅ埨愞䳸⎰嗽 ␴apixaban䘬㳣⿏炻䃞暨㊩临廠㲐ẍ䵕㊩℞ 䘬╖㟒㈿橼3, 15ˤIdarucizumab䘬䫔ᶱ昶㭝娎槿 喍䈑㓰㝄28ˤ⛐2018⸜炻伶⚳梇⑩喍䈑䭉䎮⯨ ⛐2015␴2017⸜↮⇍䘤堐Ḯ⇅㬍␴㚨䳪䳸㝄炻 㟠ⅮḮ㬌喍ἧ䓐㕤rivaroxaban␴apixaban䚠斄 栗䣢idarucizumab傥⣈⛐4⮷㗪ℏ彭忇侴㊩临⛘ ⿏⦩傭䓇␥ㆾ侭䃉㱽㍏⇞䘬↢埨ᷕ27ˤ⛐2019 旵Ỷ㷠暊dabigatran䘬㽫⹎炻᷎⚆⽑ↅ埨≇傥23, ⸜炻andexanet alfa䘬冐⸲娎槿ANNEXA-4ℵ 24炻㬌娎槿ℙ㓞抬Ḯ98ỵ栙ℏ↢埨䘬か侭炻℞ 㫉栗䣢炻andexanet alfa⎗㚱㓰⛘旵Ỷ䫔⋩⚈ 㬣ṉ䌯䁢16.4%炻怈庫忶⍣斄㕤dabigatran䚠斄 ⫸㈹⇞∹䘬㳣⿏27炻⛐㬌娎槿㇨㓞抬䘬䫔⋩⚈ ⿏栙ℏ↢埨䘬䞼䨞㇨⟙⏲䘬35%-41%Ἦ⼿Ỷ3, 24, ⫸㈹⇞∹(rivaroxabanˣapixabanˣedoxaban␴ 25ˤ⛐Ṇ㳚冐⸲ἧ䓐䴻槿㕡朊炻ᶨᾳ⎘䀋䘬䞼 enoxaparin)䚠斄⿏♜慵↢埨䘬か侭ᷕ炻㚱崭忶 䨞㓞抬Ḯ11ỵἧ䓐dabigatranᶼ䘤䓇♜慵↢埨␴ ⋲㔠䘬䕭Ṣ䁢栙ℏ↢埨炻ṾᾹ30⣑䘬㬣ṉ䌯䁢 暨天䵲⿍ㇳ埻ㆾ侭埨㞻㹞妋∹䘬䕭Ṣ炻䘤䎦⛐ 14%ˤ䃞侴炻暨㲐シ䘬㗗炻㬌䞼䨞⶚㌺昌Ḯ♜ ἧ䓐idarucizumab⼴炻か侭䘬ↅ埨≇傥⛯㚱⚆ 慵儎↢埨䘬䕭Ṣ(⊭⏓埨⟲崭忶60㮓⋯⍲㖷徟㊯ ⽑炻忁11Ṣᷕ㚱2ỵ冒䘤⿏ICH䘬か侭炻℞埨⟲ 㔠⮷㕤7↮侭)27ˤ⎎⢾炻䘤䓇埨䭉㞻⠆ḳẞ䘬㨇 䘮㰺㚱㒜⣏䘬ね⼊26ˤ⛐2015⸜㗪炻伶⚳梇⑩ 䌯䁢10%27ˤ 喍䈑䭉䎮⯨(FDA)㟠ⅮḮidarucizumab䘬ἧ䓐炻 䚖⇵炻andexanet alfa⯂㛒⛐⎘䀋ᶲⶪ炻劍 侴⛐2018⸜炻⎘䀋‍ᾅ夷䭬ḇ⮯idarucizumab䲵 䘤䓇䫔⋩⚈⫸㈹⇞∹䚠斄ICH㗪炻昌Ḯㅱ䩳⌛ ℍ䴎Ẁ炻⛐㚵䓐dabigatran䘬か侭䘤䓇暨天䵲⿍ 㙓 䫔⋩⚈⫸㈹⇞∹䘬ἧ䓐ᷳ⢾炻⛐䃉䈡⭂⍵ ㇳ埻ㆾ侭⦩傭䓇␥ㆾ䃉㱽㍏⇞䘬↢埨㗪炻⎗ẍ 廱∹䘬䉨㱩ᶳ炻⎗侫ㄖ䴎Ḱか侭㭷℔㕌50╖ỵ ἧ䓐ˤ 䘬⚃⚈⫸ↅ埨愞墯⎰㽫䷖䈑炻ㆾ侭㳣⊾ↅ埨愞 䔞䘤䓇dabigatran䚠斄⿏儎↢埨㗪炻ㅱ䩳⌛ 墯⎰㽫䷖∹ˤ㟡㒂忶⍣≽䈑⮎槿ˣ‍⹟⍿娎侭 㙓 dabigatran䘬ἧ䓐炻᷎ẍ朄傰㲐⮬䘬㕡⺷炻 䘬䞼䨞ẍ⍲暞㗇䘬ᾳ㟰⟙⮶炻ↅ埨愞墯⎰㽫䷖ ↮ㆸℑ∹䴎Ḱℙ5℔⃳䘬idarucizumab15炻劍䃉 䈑␴㳣⊾ↅ埨愞墯⎰㽫䷖∹℟㚱⚆⽑䫔⋩⚈⫸ 㱽⍾⼿idarucizumab炻⇯⎗侫ㄖ䴎Ḱↅ埨愞墯 ㈹⇞∹㈿ↅ埨䘬㓰㝄炻䃞侴䚖⇵⯂ᶵ㶭㤂墄⃭ ⎰㽫䷖䈑ㆾ侭㳣⊾ↅ埨愞墯⎰㽫䷖∹(activated ↅ埨⚈⫸㗗⏎⼙枧䫔⋩⚈⫸㈹⇞∹䚠斄ICH䘬 PCC)ẍ⚆⽑ↅ埨≇傥15 (堐1)炻䃞侴炻暨㲐シ䘤 枸⼴15ˤ⎎⢾炻䴎Ḱ50℔⃳䘬㳣⿏䡛Ṏ㚱㨇㚫 䓇埨䭉㞻⠆ḳẞ䘬㨇㚫䁢0.7%-10%15ˤ䚖⇵炻 傥䦣昌ℑ⮷㗪ℏ㚵䓐侴⯂㛒⏠㓞䘬䫔⋩⚈⫸㈹ ẍↅ埨愞墯⎰㽫䷖䈑⚆⽑dabigatran㇨忈ㆸ䘬㈿ ⇞∹15 (堐1)ˤ ↅ埨㓰㝄䘬嫱㒂ᷣ天Ἦ冒≽䈑⮎槿冯‍⹟⍿娎 શĩũŦűŢųŪůĪم侭15炻℞⮵㕤dabigatran䚠斄ICH䘬枸⼴㗗⏎㚫 ĵįġ 䓊䓇⼙枧ṵ㚱⼭慸㶭ˤ⛐䃉㱽ἧ䓐idarucizumab 㗪炻旵Ỷ橼ℏdabigatran㽫⹎䘬㕡㱽怬⊭㊔埨㵚 ⁛䴙✳偅䳈炷unfractionated heparin炸䁢ᶨ 德㜸15炻侴劍喍∹䁢2⮷㗪ℏ㚵䓐炻⎗ἧ䓐⎋㚵 啱䓙㈿ↅ埨愞嶗⼹㈹⇞䫔⋩⚈⫸␴ↅ埨愞ẍ忼 㳣⿏䡛䦣昌偫墉⯂㛒⏠㓞䘬喍䈑15 (堐1)ˤ ⇘㈿ↅ埨ἄ䓐䘬喍䈑15炻℞喍䈑⋲堘㛇䁢60-90 䫔⋩⚈⫸㈹⇞∹⊭⏓Ḯrivaroxabanˣ ↮揀炻冐⸲ᶲ炻忂ⷠẍ㳣⊾悐↮ↅ埨㳣愞㗪攻 apixaban␴edoxaban䫱喍䈑ˤAndexanet alfa䁢 (activated partial thromboplastin time, APTT)Ἦ䚋 慵䳬⼴䘬䫔⋩⚈⫸炻⬫⎗ẍ㚱㓰⛘␴䫔⋩⚈⫸ 㷔喍䈑㓰㝄᷎婧㔜ἧ䓐∹慷6ˤ⁛䴙✳偅䳈䘬⍵ ㈹⇞∹䳸⎰ẍ旵Ỷ℞橼ℏ㳣⿏炻⍵廱㈿ↅ埨㓰 廱∹炻protamine sulfate (欂䱦噳䘥)炻䁢䓙欂栆 㝄27ˤ⛐2015⸜㗪炻㕤‍⹟⍿娎侭ᷕ䘬䞼䨞㊯ 䱦⫸ᷕ厫⍾侴ㆸ䘬噳䘥岒炻≽䈑⮎槿ˣ㕤‍⹟

187 ݽᕛސ᛾ޟသюՖܒᏗՖᏘࣺᜰת

⍿娎侭䘬䞼䨞ẍ⍲ᾳ㟰⟙⮶栗䣢炻protamine⎗ 㮓⃳enoxaparin⎗旵Ỷ军0.5㮓⃳protamineˤ⛐ 冯⁛䴙✳偅䳈䳸⎰侴旵Ỷ℞㈿ↅ埨ἄ䓐15, 29烊⽫ dalteparinˣnadroparin␴tinzaparin䚠斄⿏儎↢ 冇丆忻ㇳ埻䘬冐⸲娎槿⇯栗䣢炻protamine⎗旵 埨䘬䉨㱩ᶳ炻㭷100䫔⋩⚈⫸㈹⇞╖ỵ炻⎗䴎 Ỷ埻⼴↢埨慷⍲廠埨暨㯪30ˤ㭷㮓⃳protamine Ḱ1㮓⃳protamineἄ䁢⍵廱∹15ˤ⛐䃉㱽⍾⼿ ⎗␴80-120╖ỵ偅䳈䳸⎰炻℞⋲堘㛇䲬䁢7↮ protamine䘬䉨㱩ᶳ炻⎗侫ㄖἧ䓐慵䳬䫔ᶫↅ埨 揀炻⚈㬌炻⛐⁛䴙✳偅䳈䚠斄⿏儎↢埨䘬䕭 ⚈⫸(recombinant factor VIIa) (堐1)ˤ忶⍣≽䈑 Ṣᷕ炻劍偅䳈䁢2-3⮷㗪ℏ䴻朄傰㲐⮬ἧ䓐炻 ⮎槿栗䣢炻慵䳬䫔ᶫↅ埨⚈⫸⎗⍵廱Ỷ↮⫸慷 ⺢嬘ὅ㒂偅䳈䘬ἧ䓐慷炻㭷100╖ỵ偅䳈䴎Ḱ 偅䳈䘬㈿ↅ埨ἄ䓐᷎旵Ỷ↢埨慷炻暞㗇ᾳ㟰⟙ 1㮓⃳protamine炻䁢Ḯ旵Ỷ䚠斄∗ἄ䓐炻⤪忶 ⮶Ṏ㍸⍲栆Ụἄ䓐炻䃞侴忶⍣䞼䨞㷔娎䳸㝄᷎ 㓷⍵ㅱˣ埨⡻旵Ỷˣ⽫嶛嬲ㄊ␴㯋䭉㓞䷖䫱 ᶵ⬴ℐᶨ农15, 32ˤ⚈䁢慵䳬䫔ᶫↅ埨⚈⫸㚱庫檀 桐晒炻ㅱ䚉慷㓦ㄊ廠㲐忇⹎15ˤ⚈protamine㛔 䘬埨䭉㞻⠆桐晒炻⚈㬌᷎ᶵ⺢嬘 䁢䫔ᶨ䶂ἧ 幓Ṏ㚱庽⽖㈿ↅ埨ἄ䓐炻⛐忶慷㗪⎗傥䓊䓇㈿ 䓐喍䈑15ˤ ↅ埨ἄ䓐炻⚈㬌㭷10↮揀ᶵㅱ䴎Ḱ崭忶50㮓⃳ Fondaparinux䁢ᶨ⎰ㆸḼ䡛䱾炻℞ἄ䓐冯 15ˤ⛐廠㲐protamine⼴炻ㅱ㊩临徥希㳣⊾悐↮ 偅䳈栆Ụ炻⬫䘬㈿ↅ埨㨇廱䁢啱䓙㈿ↅ埨愞嶗 ↅ埨㳣愞㗪攻(⤪㭷ᶱ⮷㗪㷔慷ᶨ㫉)炻劍ṵ檀 ⼹㈹⇞䫔⋩⚈⫸侴忼ㆸ炻䚖⇵㰺㚱喍䈑⎗ẍ 㕤㬋ⷠῤ炻ᶼ↢埨㊩临炻⇯⎗侫ㄖ䴎Ḱ䫔Ḵ∹ ⍵廱fondaparinux䘬㓰㝄ˤ䃞侴炻Ἦ冒≽䈑⮎ protamine炻㬌㗪炻∹慷䁢䫔ᶨ∹䘬ᶨ⋲(㭷100 槿ˣ‍⹟⍿娎侭冯ᾳ㟰⟙⏲䘬䞼䨞栗䣢炻䴎Ḱ ╖ỵ偅䳈䴎Ḱ0.5㮓⃳protamine)15, 31ˤ劍偅䳈䁢 㳣⊾ↅ埨愞墯⎰㽫䷖∹␴慵䳬䫔ᶫↅ埨⚈⫸Ụ 䙖ᶳ㲐⮬炻⇯ὅ㒂㳣⊾悐↮ↅ埨㳣愞㗪攻⺞攟 ᷶⎗ẍ⸓≑⚆⽑ↅ埨≇傥冯旵Ỷ䚠斄↢埨䘬↢ 冯⏎㕥ㇻprotamine (堐1)ˤ 埨慷炻侴㳣⊾ↅ埨愞墯⎰㽫䷖∹䘬㓰㝄Ụ᷶ Ỷ↮⫸慷偅䳈䁢䴻䲼⊾⼴䘬偅䳈炻冯⁛ 庫慵䳬䫔ᶫↅ埨⚈⫸Ἦ⼿⤥15ˤ⚈㬌炻⛐忯ᶲ 䴙偅䳈䚠㭼炻㑩㚱㚜⮷䘬↮⫸慷␴㚜䨑⭂䘬 fondaparinux䚠斄ICH㗪炻⎗ἧ䓐㭷℔㕌20╖ỵ 喍䈑≽≃⬠炻⛐ἧ䓐ᶲᶵ暨䚋㷔㳣⊾悐↮ↅ 䘬㳣⊾ↅ埨愞墯⎰㽫䷖∹炻⛐䃉㱽⍾⼿㳣⊾ↅ 埨㳣愞㗪攻6ˤỶ↮⫸慷偅䳈⊭㊔enoxaparinˣ 埨愞墯⎰㽫䷖∹䘬䉨㱩ᶳ炻⇯⎗侫ㄖἧ䓐㭷℔ dalteparinˣnadroparin␴tinzaparin䫱喍䈑ˤ䚖 㕌90⽖⃳䘬慵䳬䫔ᶫↅ埨⚈⫸15 (堐1)ˤ ⇵炻冐⸲ᶲ㰺㚱憅⮵Ỷ↮⫸慷偅䳈㇨姕妰䘬⍵ 廱∹炻侴protamine⮵Ỷ↮⫸慷偅䳈䘬ἄ䓐忶 ĶįġѮᢊ୊߳ೣጒ ⍣㚦⛐≽䈑⮎槿ˣ‍⹟⍿娎侭␴ᾳ㟰⟙⮶ᷕ 㷔娎炻䞼䨞㊯↢protamine⍵廱Ỷ↮⫸慷偅䳈 䓙㕤⎬⺷⍵廱∹⛐㈿ↅ埨∹䚠斄⿏儎↢埨 䘬㓰㝄炻⛐⎬ᾳᶵ⎴喍䈑ᷕ炻㚫ὅ㒂℞↮⫸䳸 ᷕ䘬ἧ䓐㓰㝄冯嫱㒂ᶵ䚉䚠⎴炻⚈㬌‍ᾅ夷䭬 㥳␴㈹⇞䘬ↅ埨⚈⫸ᶵ⎴侴㚱㇨ⶖ䔘15ˤᶨ凔 ⛐䴎Ẁᶲḇ㚱㇨ⶖ䔘ˤ⯙憅⮵䈡⭂喍䈑䘬⍵廱 侴妨炻protamine傥⣈庫⤥⛘⚆⽑㈿ↅ埨愞䘬 ∹侴妨炻䚖⇵‍ᾅ䴎Ẁ㚱䵕䓇䳈K㕤䵕䓇䳈K㊖ 㓰㝄炻侴䃉㱽⬴ℐ微廱䫔⋩⚈⫸⍿㈹⇞䘬ね⼊ ㈿∹䚠斄ICH㗪ἧ䓐烊Idarucizumab㕤dabigatran 29ˤ⎎⢾炻悐↮ᾳ㟰⟙⮶㊯↢炻ἧ䓐protamine 䚠斄ICH㗪䴎Ḱ烊ẍ⍲protamine㕤㲐⮬偅䳈侴 ⎗旵ỶỶ↮⫸慷偅䳈䚠斄↢埨䘬↢埨慷15, 32ˤ ↢埨䘬䕭Ṣ炻⛐暨⍵廱偅䳈䘬ἄ䓐㗪ἧ䓐ˤ⛐ 䚖⇵炻⛐enoxaparin䚠斄⿏儎↢埨ᷕ炻劍 埨㵚墥⑩䘬悐↮炻‍ᾅ䚖⇵䴎Ẁ㚱ↅ埨愞墯⎰ ㈿ↅ埨∹㕤8⮷㗪ℏἧ䓐炻㭷㮓⃳enoxaparin 㽫䷖䈑㕤䵕䓇䳈K㊖㈿∹䚠斄ICH䘬䕭Ṣˤ䃞侴 ⎗䴎Ḱ1㮓⃳protamine 䁢⍵廱∹炻侴劍喍䈑 ⛐℞⬫䧖栆䘬㈿ↅ埨∹䘤䓇䚠斄⿏儎↢埨㗪炻 㕤8-12⮷㗪ℏἧ䓐炻⇯protamine䘬㲐⮬慷炻㭷 㕥ㇻᶲ⇯⽭枰冒屣ˤ㕘歖⅟ⅵ埨㻧䚖⇵‍ᾅ䴎

188 ݽᕛސ᛾ޟသюՖܒᏗՖᏘࣺᜰת

堐1ˢ㈿ↅ埨喍䈑䚠斄⿏儎↢埨䘬喍䈑㱣䗪㕡⺷

㈿ↅ埨喍䈑 㱣䗪㕡⺷

䵕䓇䳈K㊖㈿∹烉 1. 䴎Ḱ10 mg朄傰㲐⮬䵕䓇䳈K⍲25-50 U/Kg PCCˤ Warfarin 2. 劍䃉㱽⍾⼿PCC炻⎗ẍ10-15 ml/Kg FFP⍾ẋPCCˤ 3. ℵ㫉䡢娵 INRῤ炻劍24-48⮷㗪ℏ㛒忼䚖㧁ῤ(⤪< 1.4)炻⎗ℵ䴎Ḱ10 mg 朄傰㲐⮬䵕䓇䳈K⍲FFPˤ

Dabigatran 1. 䴎Ḱ朄傰㲐⮬5 g Idarucizumabˤ 2. 劍䃉㱽⍾⼿ Idarucizumab炻⎗侫ㄖ䴎Ḱ50 U/Kg PCCㆾ侭activated PCC炻Ṏ⎗侫ㄖẍ㲿僶㕡⺷䦣昌dabigatranˤ 3. 劍dabigatran䁢2⮷㗪ℏ㚵䓐炻⎗侫ㄖ䴎Ḱ50 g㳣⿏䡛ˤ

䫔⋩⚈⫸㈹⇞ 1. 劍䁢 rivaroxabanㆾ侭apixaban䚠斄⿏儎↢埨炻⎗䴎Ḱandexanet alfa (䚖 ∹䘬NOACs烉 ⇵⎘䀋⯂䃉㬌喍)ˤ Rivaroxabanˣ 2. ⛐䃉䈡⭂⍵廱∹㗪炻⎗侫ㄖ䴎Ḱ 50 U/Kg PCCㆾ侭activated PCCˤ ApixabanˣEdoxaban 3. 劍喍䈑䁢 2⮷㗪ℏ㚵䓐炻⎗侫ㄖ䴎Ḱ50 g㳣⿏䡛ˤ

⁛䴙✳偅䳈烉Heparin 1. 劍䁢䙖ᶳ㲐⮬ᷳ heparin炻⇯䡢娵aPTTῤ炻ὅ㒂aPTTῤ䴎Ḱprotamineˤ 2. 劍䁢朄傰㲐⮬ᷳ heparin炻⇯㭷100 U偅䳈䴎Ḱ1 mg protamine炻᷎夷⇯ 䚋㷔aPTTῤ(⤪㭷3⮷㗪)炻劍ṵ⺞攟炻㭷100 U偅䳈⎗侫ㄖℵ䴎Ḱ0.5 mg protamineˤ

Ỷ↮⫸慷偅䳈烉 ὅ㒂Enoxaparin䴎Ḱ㗪攻㕥ㇻprotamine烉劍䁢8⮷㗪ℏ炻⇯1 mg Enoxaparin enoxaparin䴎Ḱ1 mg protamineˤ劍䁢8-12⮷㗪炻⇯1 mg enoxaparin䴎Ḱ0.5 mg protamineˤ

Ỷ↮⫸慷偅䳈烉 1. 㭷100 U䫔⋩⚈⫸㈹⇞∹炻⎗䴎Ḱprotamine 1mgˤ Dalteparinˣ 2. 劍䃉protamine炻⎗侫ㄖẍ慵䳬䫔ᶫ⚈⫸㚧ẋᷳˤ NadroparinˣTinzaparin

Fondaparinux 1. 侫ㄖ䴎Ḱ20 U/Kg aPCCˤ 2. 劍䃉㱽⍾⼿aPCC炻侫ㄖ䴎Ḱ90 mcg/Kg慵䳬䫔ᶫ⚈⫸ˤ

NOAC烉朆䵕䓇䳈K㊖㈿∹⎋㚵㈿ↅ埨∹烊aPTT烉㳣⊾悐↮ↅ埨愞⍇㗪攻烊PCC烉ↅ埨愞墯⎰㽫 ䷖䈑烊FFP烉㕘歖⅟ⅵ埨㻧ˤ

Ẁ㕤ↅ埨愞⍇㗪攻(PT)ㆾ侭㳣⊾悐↮ↅ埨㳣愞 㓰㝄炻旵Ỷ↢埨慷炻ṵ㚱㨇㚫⎗㓡┬枸⼴14ˤ 㗪攻⺞攟1.5᾵ᶼ㚱↢埨⁦⎹ㆾ侭暨天ㇳ埻ㆾὝ 䚖⇵⛐⎋㚵㈿ↅ埨∹㕡朊炻䵕䓇䳈K㊖㈿∹␴ 多⿏㱣䗪侭炻ẍ⍲暨天䵲⿍䳪㬊warfarin䘬ἄ䓐 Dabigatran⶚㚱⍵廱∹⎗ẍἧ䓐24, 26炻侴䫔⋩⚈ 㗪ἧ䓐ˤ慵䳬䫔ᶫ⚈⫸㕤㈿ↅ埨∹䚠斄⿏儎↢ ⫸㈹⇞∹䘬⍵廱∹ḇ⶚䴻⛐伶⚳ᶲⶪ27烊⛐憅 埨ᷕ䘬㕥ㇻ炻䚖⇵䘮䃉䴎Ẁˤ ∹✳㈿ↅ埨∹悐↮炻protamine傥⣈⬴ℐ⍵廱 ⁛䴙✳偅䳈䘬㈿ↅ埨ἄ䓐炻侴⮵㕤Ỷ↮⫸慷偅 ķįġ๖ȁȁᇭ 䳈⇯㚱⻟⻙ᶵᶨ䘬⍵廱㓰㝄29ˤ昌Ḯ⍵廱∹ᷳ ⢾炻ἧ䓐埨㵚墥⑩墄⃭ↅ埨⚈⫸ḇ㗗⚆⽑ↅ埨 ㈿ↅ埨∹䚠斄⿏儎↢埨䁢ᶨ冐⸲ᶲ暋ẍ性 ≇傥䘬ᶨ䧖㕡㱽炻䚖⇵炻ẍ埨㵚墥⑩⍵廱㈿ↅ ⃵䘬䵲⿍䉨㱩炻ᶼ䴻ⷠ⮶农♜慵䘬≇傥⿏ ⭛ 埨ἄ䓐ẍ㓡┬㈿ↅ埨∹䚠斄⿏儎↢埨䘬枸⼴ ␴檀㬣ṉ䌯2, 8炻䃞侴劍傥⍲㖑⍵廱㈿ↅ埨∹䘬 䘬ᷣ天嫱㒂炻⛐⣂㔠㈿ↅ埨∹ᷕ炻Ἦ冒≽䈑⮎

189 ݽᕛސ᛾ޟသюՖܒᏗՖᏘࣺᜰת

槿ˣ‍⹟⍿娎侭␴ᾳ㟰⟙⏲炻℞㓰㝄ῤ⼿㚜⣂ 223. doi: 10.1186/cc13889. 䞼䨞㍊妶ᷳ15ˤ 8. Chen SJ, Yeh SJ, Tang SC, Lin SY, Tsai LK, Jeng JS. Similar outcomes between ୤ՃМᝦ vitamin K and non-vitamin K antagonist oral anticoagulants associated intracerebral 1. Meretoja A, Strbian D, Putaala J, et al. hemorrhage. J Formos Med Assoc 2019 Mar SMASH-U: a proposal for etiologic 12. pii: S0929-6646(18)30521-7. doi: 10.1016/ classification of intracerebral hemorrhage. j.jfma.2019.02.008. Stroke 2012;43:2592-2597. doi: 10.1161/ 9. Purrucker JC, Haas K, Rizos T, et al. Early STROKEAHA.112.661603. clinical and radiological course, management, 2. Yeh SJ, Tang SC, Tsai LK, Jeng JS. and outcome of intracerebral hemorrhage Pathogenetical subtypes of recurrent related to new oral anticoagulants. JAMA intracerebral hemorrhage: designations Neurol 2016;73:169-177. doi: 10.1001/jamaneurol. by SMASH-U classification system. 2015.3682. Stroke 2014;45:2636-2642. doi: 10.1161/ 10. Kuramatsu JB, Gerner ST, Schellinger PD, STROKEAHA.114.005598. et al. Anticoagulant reversal, blood pressure 3. Steiner T, Weitz JI, Veltkamp R. Anticoagulant- levels, and anticoagulant resumption in patients associated intracranial hemorrhage in the era with anticoagulation-related intracerebral of reversal agents. Stroke 2017;48:1432-1437. hemorrhagetreating anticoagulation-related doi: 10.1161/STROKEAHA.116.013343. intracerebral hemorrhagetreating anticoagulation- 4. Ruff CT, Giugliano RP, Braunwald E, et al. related intracerebral hemorrhage. JAMA 2015; Comparison of the efficacy and safety of new 313:824-836. doi: 10.1001/jama.2015.0846. oral anticoagulants with warfarin in patients 11. Flibotte JJ, Hagan N, O'Donnell J, Greenberg with atrial fibrillation: a meta-analysis of SM, Rosand J. Warfarin, hematoma expansion, randomised trials. Lancet 2014;383:955-962. and outcome of intracerebral hemorrhage. doi: 10.1016/S0140-6736(13)62343-0. Neurology 2004;63:1059-1064. doi: 10.1212/ 5. Yasaka M, Lip GY. Impact of non-vitamin k 01.wnl.0000138428.40673.83. antagonist oral anticoagulants on intracranial 12. Hemphill JC, 3rd, Greenberg SM, Anderson bleeding in Asian patients with non-valvular CS, et al. Guidelines for the management atrial fibrillation. Circ J 2014;78:2367-2372. of spontaneous intracerebral hemorrhage: A doi: 10.1253/circj.cj-14-0720. guideline for healthcare professionals from the 6. Antman EM, Morrow DA, McCabe CH, et American Heart Association/American Stroke al. Enoxaparin versus unfractionated heparin Association. Stroke 2015;46:2032-2060. doi: with fibrinolysis for st-elevation myocardial 10.1161/STR.0000000000000069. infarction. N Engl J Med 2006;354:1477-1488. 13. Bechtel BF, Nunez TC, Lyon JA, Cotton doi: 10.1056/NEJMoa060898. BA, Barrett TW. Treatments for reversing 7. Ray B, Keyrouz SG. Management of warfarin anticoagulation in patients with acute anticoagulant-related intracranial hemorrhage: intracranial hemorrhage: a structured literature an evidence-based review. Crit Care 2014;18: review. Int J Emerg Med 2011;4:40. doi: 10.

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NEJMoa1814051. complete, partial, or no reversal? Cardiovasc 28. Siegal DM, Curnutte JT, Connolly SJ, et al. Surg 2002;10:245-250. Andexanet alfa for the reversal of factor Xa 31. Cushman M, Lim W, Zakai NA. 2011 Clinical inhibitor activity. N Engl J Med 2015;373:2413- practice guide on anticoagulant dosing and 2424. doi: 10.1056/NEJMoa1510991. management of anticoagulant-associated 29. Steiner T, Salman RA-S, Beer R, et al. bleeding complications in adults. American European Stroke Organisation (ESO) Society of Hematology 2011. guidelines for the management of spontaneous 32. Byrne M, Zumberg M. Intentional low- intracerebral hemorrhage. Int J Stroke 2014;9: molecular-weight heparin overdose: a case 840-855. doi: 10.1111/ijs.12309. report and review. Blood Coagul Fibrinolysis 30. Gatti G, Pugliese P. Heparin reversal in 2012;23:772-774. doi: 10.1097/MBC.0b013e off-pump coronary artery bypass surgery: 328358e8af.

192 ݽᕛސ᛾ޟသюՖܒᏗՖᏘࣺᜰת

Medication Treatment in Anticoagulant-Associated Intracerebral Hemorrhage

Szu-Ju Chen1, 2, Shin-Yi Lin3, Li-Kai Tsai1

1 Department of Neurology, National Taiwan University Hospital, Taipei, Taiwan 2 Department of Neurology, National Taiwan University Hospital Bei-Hu Branch, Taipei, Taiwan 3 Department of Pharmacy, National Taiwan University Hospital, Taipei, Taiwan

ABSTRACT

Anticoagulant-associated intracerebral hemorrhage (ICH) is one of the major causes of spontaneous ICH. Studies reported that anticoagulant-associated ICH (AICH) accounted for up to 14% of spontaneous ICH in western population and 2.6% in Taiwan. AICH had the worst prognosis among all causes of spontaneous ICH. The mortality was estimated at 60% and less than 20% of patients could walk independently at 3-months post ICH. Reversing anticoagulant effect was considered the cornerstone of treating AICH. Reducing activity of anticoagulant may lead to a smaller hematoma volume and better prognosis. Sine various anticoagulants work through different mechanisms, the reversal method differs. Vitamin K antagonist was the most common oral anticoagulant that works by inhibiting vitamin K-associated coagulation factors. Prescribing Vitamin K and prothrombin complex concentrate (PCC) is the first-line treatment of vitamin K antagonist-associated ICH. Non-vitamin K antagonist oral anticoagulants could be classified into direct thrombin inhibitor and factor Xa inhibitor. Idarucizumab is the reversal agent of the direct thrombin inhibitor, dabigatran, and should be prescribed immediately in dabigatran-related ICH. As for factor Xa inhibitors, rivaroxaban, apixaban, and edoxaban, the reversal agent, andexanet alpha, has been developed and approved by FDA but not widely available yet. Before a reversal agent could be achieved, PCC should be considered in factor Xa inhibitor-associated ICH. Protamine is the reversal agent of heparin, and should be given in heparin-associated ICH though the efficacy differs in different types of heparin.

Keywords: Anticoagulants, Intracerebral hemorrhage, Reversal agents, Stroke

Corresponding author: Dr. Li-Kai Tsai, Stroke Center & Department of Neurology, National Taiwan University Hospital, No 7, Chung-Shan South Road, Taipei 100, Taiwan, R.O.C. E-mail: [email protected]

193 ᆣġġ፣ ijıIJĺԑĹТѕୢသϛॳᚖТོʼnŪŨũŭŪŨũŵ

ijıIJĺԑĹТѕୢသϛॳᚖТོʼnŪŨũŭŪŨũŵ

׹࿤ؼǵഋѓጎǵഋ࢙ᓄ

2019⸜8㚰11㖍䘬⊿⋨儎ᷕ桐暁㚰㚫炻䈡 䕯⼰⣂ˤ㊯⺽㕤2013⸜⮯㱣䗪㡅ẞ㓦⮔炻怑䓐 ⇍怨婳⊿Ṕ⣑⡯慓昊䤆䴻ℏ䥹䘬㜄叔列㔁㌰㺼 㗪攻ḇ婧㔜䁢ᷕ桐䘤ἄ4.5⮷㗪ℏ炻⸜漉䁢18㬚 嫃炻㜄㔁㌰⍣⸜㚦Ἦ⎘炻Ṿ䓇≽⸥満⍰傥⺽ ẍᶲ炻Ữ3-4.5⮷㗪ṵ㚱䚠⮵䤩⽴䕯炻娚㊯⺽㕤 崟ℙ沜䘬㺼嫃㶙䌚⤥姽炻⚈㬌Ṳ⸜⬠㚫ℵ㫉 2018⸜㚜⮯IVT㡅ẞ忚ᶨ㬍攳㓦㕤䈡⭂ね㱩䘬 怨婳㕤8㚰10㖍⛐⎘⋿ˣ8㚰11㖍⛐⎘⊿冱彎㺼 庽⹎ᷕ桐⎗ἧ䓐炻ᶼ䤩⽴䕯ḇ⎴㬍㷃⮹炻ἳ⤪ 嫃炻Ṿ㺼嫃䘬柴䚖䁢ˬ㹞㞻䘬⮎⊁冯㈨ⶏ˭炻 栙ℏ儓䗌ˣ⮷䘬ㆾ㗗ᷕ䫱⣏⮷䘬栙ℏ㛒䟜塪≽ ⎴㗪ḇ怨婳倗㕘⚳晃慓昊䘬昛⎛䶗慓ⷓᷣ嫃 傰䗌ẍ⍲栙⢾柠≽傰∅暊䘮⎗忚埴IVT㱣䗪ˤ ˬ⿍⿏仢埨ᷕ桐朄傰埨㞻㹞妋㱣䗪(intravenous 㟡㒂2016⸜Whiteley䫱Ṣ䘬䞼䨞炻⮯䕭 thrombolysis, IVT)㊯⺽˭ˣ冯⎘ᷕ㥖䷥䘬昛㝷 かὅ♜慵䦳⹎↮䁢Ḽ栆炻㟡㒂䴙⎰↮㜸(meta- 暾慓ⷓᷣ嫃ˬ⿍⿏仢埨ᷕ桐ℵ㿴㳩㱣䗪䘬䨩䟜 analysis)䘬䳸㝄炻IVT㱣䗪⮵㕤庽⹎ᷕ桐䘬䳸㝄 ⿏䞼䨞˭炻ℏ⭡䱦⼑炻䈡㔜䎮⤪ᶳˤ 㚨⤥炻ᷕ桐♜慵䦳⹎㚨庽䘬䳬⇍䚠庫㕤⮵䄏䳬 㚱列⤥枸⼴䘬㭼ἳ㚜檀炻ᶼIVT⼴䘬㬣ṉ䌯䃉 ᄂ୛ᇄ׬ѽ 栗叿⡆≈1炻⤪堐1㇨䣢ˤޟIJįġྙ੃

Ṕ⣑⡯慓昊䤆䴻ℏ䥹 㜄叔列慓ⷓ IJįijįġŊŗŕݽᕛ࡟၌ؚϞ୰ᚠ⊿ 姙⣂䜉愺䘤䎦ᷕ桐(wake-up stroke)䘬䕭Ṣ IJįIJįġŊŗŕޟี৤ ṵ⎗傥怑⎰IVT㱣䗪炻ἧ⼿忁悐↮䘬䞼䨞㚱䘤 1996⸜伶⚳⽫冇⬠㚫/伶⚳ᷕ桐⬠㚫䘬⿍ ⯽䨢攻炻ἳ⤪⛐WAKE-UP䞼䨞␴EXTEND䞼䨞 ⿏仢埨ᷕ桐㊯⺽炻IVT⺢嬘䘬怑䓐㕷佌䁢䘤䓇 德忶⣂㧉⺷㟠䡩ℙ㋗䫱⼙⁷(magnetic resonance ᷕ桐3⮷㗪ℏ炻⸜漉䁢18⇘80㬚ᷳ攻炻ᶼ䤩⽴ image, MRI)Ἦ⇌㕟䕭か㗗⏎怑䓐IVT㱣䗪2, 3ˤ

堐1ˢ庽⹎ᷕ桐冯♜慵ᷕ桐⮵㕤IVT㱣䗪䘬䳸㝄

NIHSS 0-4 NIHSS ʁ 22

♜慵䦳⹎ 㚨庽 㚨♜慵

Alteplase䳬烉34.6% Alteplase䳬烉0.5% ᶱᾳ㚰列⤥䳸㝄(mRS 0-1) ⮵䄏䳬烉26.8% ⮵䄏䳬烉0.3%

Alteplase䳬烉2.4% Alteplase䳬烉46.2% ᶱᾳ㚰㬣ṉ(mRS 6) ⮵䄏䳬烉2.2% ⮵䄏䳬烉44.1% NIHSS: National Institute of Health Stroke Scale ; mRS: modified Rankin Scale.

DOI: 10.6318/FJS.201912_1(3).0003

194 ijıIJĺԑĹТѕୢသϛॳᚖТོʼnŪŨũŭŪŨũŵ

ીՖϛॳŊŗŕݽᕛࡾЕܒ䃞侴炻᷎朆㇨㚱䕭か䘬⋲⼙⋨(penumbra)㕤3⮷ ijįġࡨ 㗪⼴⬴ℐ㴰⣙炻䚜⇘ᷕ桐䘤ἄ18-24⮷㗪⼴ṵ㚱 44%䘬か侭℟㚱⋲⼙⋨炻㓭⮯2015⸜䘬伶⚳⿍ 倗㕘⚳晃慓昊䤆䴻ℏ䥹 昛⎛䶗慓ⷓ ⿏仢埨儎ᷕ桐㊯⺽ᷳ⺢嬘㱣䗪㕷佌(䘤䓇ᷕ桐䕯 ὅ㒂⎘䀋儎ᷕ桐䘣抬屯㕁栗䣢炻80%ᷕ桐 䉨6⮷㗪ℏ䘬䕭か)㕤2018⸜㓦⮔军䘤䓇ᷕ桐24 Ⱄ㕤仢埨ᷕ桐4ˤ㚱揺㕤㬌炻⎘䀋儎ᷕ桐⬠㚫⍫ ⮷㗪ℏˤ晾䃞㚱⋲⼙⋨䘬䕭か㭼ἳ晐叿㗪攻⺞ 侫2018⸜伶⚳⽫冇/ᷕ桐⬠㚫䘬⿍⿏仢埨ᷕ桐㱣 攟侴旵Ỷ炻Ữ㗗德忶⣂㧉⺷䘬⼙⁷慓⬠ṵ⎗䮑 䗪㊯⺽5ˣ℞Ṿ⚳⭞䘬㱣䗪㊯⺽⍲㕘役䘤堐䘬檀 怠↢怑䓐IVT䘬䕭かˤ ⑩岒䞼䨞ㆸ㝄炻ὅ㒂㱣䗪㓰䙲⻟⹎⍲嫱㒂䫱䳂 娵⭂㧁㸾炻㬠䲵↢䫎⎰⎘䀋⮎晃⎗埴䘬冐⸲⺢ 嬘⍲㱣䗪㕡⺷炻㕤2019⸜䘤堐⿍⿏仢埨ᷕ桐IVT ٴငᡛϷޟIJįĴįġŊŗŕ 㱣䗪㊯⺽炻ẍ㍸⋯⎘䀋儎ᷕ桐㱣䗪䘬⑩岒6ˤ

䴻槿↮ṓ

怑⎰IVT䘬䕭か 1. Ἦ䘬㖑烉㠿⠆㗪攻崲ᷭ炻崲㍍役⬴ℐ⿏䘬ᷕ桐炻㹞㞻崲暋䌚䙲ˤ 2. 㠿⠆⮷烉㠿⠆䘬⣏⮷␴↢埨廱⊾䘬桐晒㚱䚜㍍斄Ὢˤ 3. ℏ䥹䕭⮹烉➢䢶䕦䕭崲⮹䘬Ṣ炻㈧⍿傥≃崲⻟ˤ

⭞Ⱄ㹅忂 1. ⮰㤕埻婆䚉慷⮹炻性⃵倥ᶵㅪˤ 2. 怠㑯㧁㸾䚉慷䯉╖炻性⃵䳽⮵⊾ˤ 3. 桐晒㤪䌯䚉慷℟橼炻性⃵⿸ヴˤ 4. ⺽䓐㔠⫿䚉慷䴙ᶨ炻性⃵䔹べˤ

䕭ね妋婒 1. ⼿Ṩ湤䕭ˤ 2. ㅱ⤪ỽ㱣䗪ˤ 3. 㱣䗪ⷞἮ䘬⤥嗽ˤ 4. ⎗傥䘤䓇䘬桐晒炻Ữ㨇䌯⼰Ỷˤ ẍᶲ妋婒崲䯉╖崲⤥ˤ

⺽⮶䕭かḮ妋䕭ね 1. 㛒Ἦ≈慵䘬桐晒ˤ 2. 䔞ᶳ㰢䫾䘬従↯ˤ 3. 朊⇵慓䓇䘬⮰㤕ˤ

㹞㞻㰢䫾 1. 埨䭉⇌㕟ˤ 2. 䕭⚈姢㕟ˤ 3. 嵐⊊Ộ妰ˤ ⎗▿娎冯䕭か⭞Ⱄ⚆ㅞᷕ桐䘬䘤⯽䴻忶炻枸Ộ䕭ね䘬䘤⯽嵐⊊᷎⍾⼿㱣䗪 ℙ嬀ˤ

䘤䓇↢埨廱⊾ 1. ᶵ婯㍐㷔⍇⚈ˤ 2. 婯嗽䎮㍒㕥ˤ ㅱ⺢姕⿏䘬妶婾⼴临㱣䗪忶䦳炻⯽䎦↢婈シ冯⮰㤕炻⭞Ⱄ⣏⣂傥㍍⍿ˤ

䕭䦳℟㚱⣂嬲⿏炻㓭⛐嗽䎮㹞㞻㗪ᶵ傥㔁㡅炻ᶵ⎴ね㱩⎗傥㚱ᶵ⎴䘬嗽伖㕡⺷ˤ 㓡┬䳸⯨㗗㱣䗪䘬䳪㤝䚖䘬炻妋㰢⓷柴㗗䕭か⭞Ⱄ䘬㟠⽫姜㯪ˤ

195 ijıIJĺԑĹТѕୢသϛॳᚖТོʼnŪŨũŭŪŨũŵ

2.1 ⿍⿏儎㠿⠆䘤ἄ 3⮷㗪ℏ炻NIHSS 4-25↮炻 ᶵ㚫栗叿⡆≈䘤䓇䕯䉨儎↢埨(symptomatic 䃉℞Ṿ䤩⽴䕯侭怑䓐IVT㱣䗪(Class I, Level intracerebral hemorrhage, sICH)䘬桐晒1ˤ of Evidence A)ˤ 2008-2017⸜⎘䀋16⭞慓昊䘬⚆栏⿏䞼䨞炻 ⛐㰺㚱䤩⽴䕯䘬ね㱩ᶳ炻ẍ朄傰㲐⮬ 374⎵か侭忚埴IVT㱣䗪炻34.0%䘬枸⼴列 Actilyse (rt-PA)⎗㚱㓰㍸⋯《⽑儎ᷕ桐䤆䴻 ⤥炻栗叿檀㕤⮵䄏䳬䘬22.7%炻⤪堐2 11ˤ ≇傥ᷳ⊅䬿㭼(odds ratio, OR)炻Ữ㗗rt-PA䘬 ẍᶱ䧖ᶵ⎴⭂佑䘬sICH㡅ẞ䔞ἄ⬱ℐ姽Ộ 冐⸲㱣䗪㓰䙲晐叿嶅暊儎ᷕ桐䘤䓇䘬㗪攻㉱ 㧁㸾炻⇯rt-PA䳬冯⬱ㄘ∹䳬䚠㭼䃉栗叿ⶖ 攟侴怆㷃7炻ẍˮ䙲ᶨṢ暨慓㱣㔠˯(Number 䔘炻侴ẍ⣂嬲枭⚆㬠↮㜸rt-PA䘬mRS 0-1䘬 needed to treated, NNT)Ἦ姽Ộ䗪㓰炻䓙90↮ OR忼2.39ˤ 揀ℏ䘬4-5Ṣ⡆≈军90-180↮揀䘬9Ṣˤ 2.3 ⿍⿏仢埨ᷕ桐か侭䫎⎰朄傰㲐⮬ rt-PA㱣䗪 2.2 ⿍⿏仢埨ᷕ桐か侭䫎⎰朄傰㲐⮬ rt-PA㱣䗪 夷䭬炻劍䫎⎰㿴㳩⼙⁷㚱䚠䔞⣂䘬儎䳬䷼ 夷䭬炻⸜漉ʀ80㬚ˣ㛒ἧ䓐⎋㚵㈿ↅ埨∹ˣ 仢埨Ữ⯂㛒⢆㬣,⎗侫ㄖ㕤䘤䓇4.5-9⮷㗪ℏ NIHSSʀ25↮ˣ⼙⁷⬠㩊㞍㛒栗䣢ᷕ桐䭬 ㍍⍿rt-PA㱣䗪(Class IIb, Level of Evidence ⚵崭忶ᷕ⣏儎≽傰㿴㳩⋨➇1/3ẍᶲˣ㛒⎴ B-R)ˤ 㗪㚱⃰⇵ᷕ桐⍲䱾⯧䕭⎚侭炻⎗侫ㄖ㕤䘤 WAKE-UP䞼䨞栗䣢炻䃉䡢↯ᷕ桐䘤ἄ 䓇3-4.5⮷㗪ℏ㍍⍿rt-PA㱣䗪(Class I, Level 㗪攻䘬䕭か炻劍MRI⼙⁷↢䎦DWI-FLAIR of Evidence B-R)ˤ⿍⿏仢埨⿏儎ᷕ桐䘬か mismatch炻ẋ堐䕭か㠿⠆✳ᷕ桐䘤ἄ㗪攻 侭䫎⎰朄傰㲐⮬rt-PA㱣䗪夷䭬炻劍⸜漉> 80 ⮹㕤4.5⮷㗪炻㍍⍿rt-PA㱣䗪庫⬱ㄘ∹㚱 㬚ˣㆾ㬋ἧ䓐⎋㚵㈿ↅ埨∹warfarin侴INR < 㚜Ἓ䘬枸⼴(53.3%か侭忼ᷣ天䞼䨞䳪溆炻 1.7ˣㆾ⎴㗪㚱⃰⇵ᷕ桐⍲䱾⯧䕭⎚侭炻⎗ p = 0.02)2ˤEXTEND䞼䨞㊯↢炻劍⼙⁷⬠ 侫ㄖ㕤䘤䓇3-4.5⮷㗪ℏ㍍⍿rt-PA㱣䗪(Class 栗䣢ᷕ桐䕭か儎悐㚱⋲⼙⋨炻堐䣢䕭か䘬 IIa, Level of Evidence B-R)ˤ ᷕ桐䘤ἄ㗪攻⛐4.5-9⮷㗪ᷳ攻炻35.4%䕭 Hacke䫱⍲Emberson䫱䘬䞼䨞䘮栗 か㍍⍿rt-PA㭼崟⬱ㄘ∹䳬㚱㚜⤥枸⼴(mRS 䣢炻ᷕ桐䘤ἄ3-4.5⮷㗪ℏᷳか侭忚埴IVT 0-1烉OR = 1.44炻p = 0.04烊sICH 6.2%炻p = 㱣䗪炻㔜橼䳸㝄列⤥8, 9ˤ德忶9ᾳ晐㨇娎 0.053)3ˤ 槿䘬䴙⎰↮㜸炻劍㧁㸾㓦⮔军4.5⮷㗪炻㱣 2.4 ἧ䓐朄傰㲐⮬ rt-PA㕤⸜漉18-80㬚ㆾ⣏㕤80 䗪ṵ傥栗叿⡆≈か侭《⽑⇘≇傥⸦᷶㬋ⷠ 㬚ᷳ⿍⿏仢埨ᷕ桐か侭炻⛯㍸ὃ⛐ᶱᾳ㚰 (modified Rankin Scale [mRS] 0-1)㨇㚫10ˤ ⼴䤆䴻≇傥㓡┬ᷳ⎗傥⿏烊ˬ⸜漉⣏㕤80 Stroke Thrombolysis Trialists (STT)㔜⎰↮㜸 㬚˭ᶵㅱ╖䌐ㆸ䁢㌺昌rt-PA㱣䗪䘬㊯㧁炻 栗䣢炻ẍrt-PA㱣䗪ᷕ桐䘤ἄ3-4.5⮷㗪䘬䕭 侴ㅱ䵄⎰℞Ṿ㊯㧁 㔜橼姽Ộ⼴炻嫡ヶἧ䓐 か炻冯㱣䗪ᷕ桐䘤ἄ3⮷㗪ℏᷳ䕭か䚠㭼炻 (Level I, Level of Evidence A)ˤ

堐2ˢ⿍⿏仢埨ᷕ桐3-4.5⮷㗪㍍⍿rt-PA㱣䗪䘬䳸㝄

ᷕ桐䘤ἄ㗪攻 㭼庫ἧ䓐rt-PA冯⬱ㄘ∹(㍏⇞䳬)ᷳ䳸㝄 Hacke W et al.8 3-4.5⮷㗪 mRS 0-1: OR 1.42, p = 0.04 Emberson J et al.9 3-4.5⮷㗪 mRS 0-1: OR 1.26, p = 0.0132 Hacke W et al.10 3-4.5⮷㗪 mRS 0-1: OR 1.35 Chen YW et al.12 3-4.5⮷㗪 mRS 0-1: OR 1.75, p < 0.001

196 ijıIJĺԑĹТѕୢသϛॳᚖТོʼnŪŨũŭŪŨũŵ

Emberson䫱䘬䞼䨞栗䣢炻⣏㕤80㬚か IIb, Level of Evidence B-NR)ˤ军㕤憅⮵㚵䓐 侭㍍⍿rt-PA㱣䗪℟㚱列⤥䘬枸⼴堐䎦(mRS dabigatran䘬⿍⿏仢埨⿏儎ᷕ桐か侭炻⎗侫 0-1烉OR = 1.56)9ˤ德忶8ᾳ晐㨇娎槿炻劍⮯ ㄖἧ䓐⍵廱∹idarucizumab⼴ℵ㕥ㇻ埨㞻㹞 rt-PA㫸䚇ầ╖㧁㸾㓦⮔军⸜漉⣏㕤80㬚炻 妋∹(Class IIb, Level of Evidence C-EO)ˤ ṵ傥栗叿⡆≈か侭《⽑⇘≇傥⸦᷶㬋ⷠᷳ 㟡㒂⎘⣏慓昊24⸜⿍⿏ᷕ桐䘣抬屯㕁 㨇㚫(mRS 0-1烉OR = 1.43)10ˤSTT㔜⎰↮㜸 䘤䎦炻䘤䓇儎㠿⠆䘬䕭Ṣ⌈ℐ悐⿍⿏儎埨䭉 ㊯↢炻⸜漉> 80㬚䘬か侭㕥ㇻrt-PA⼴炻ᶵ㚫 䕦䕭䕭Ṣ䘬㭼ἳ⇵⼴䚠役炻Ữ⽫㸸⿏㞻⠆⽆ ⡆≈儎↢埨䘬桐晒1ˤTTT-AIS奨⮇⿏䞼䨞 19.9%徸⸜ᶲ⋯军28.5%炻⽫㇧栓≽䘬㭼ἳ ㊯↢炻> 70㬚䘬か侭㍍⍿0.86-0.95 mg/kg䘬 ḇ䓙17.6%⋯军25.7%16ˤ㬌栆䕭か⺢嬘ἧ䓐 rt-PA㱣䗪炻䘤䓇sICH桐晒庫檀12ˤ德忶Ṍ⍱ warfarin䫱㈿ↅ埨∹Ἦ枸旚ᷕ桐ˤ䵄⎰伶⚳ ↮㜸栗䣢炻⣏㕤70㬚䘬ᷕ桐か侭ἧ䓐Ỷ∹慷 ㊯⺽⺢嬘冯䚠斄䞼䨞⟙⏲炻⎘䀋儎ᷕ桐⬠ (0.7 mg/Kg) rt-PA䘬枸⼴㭼ἧ䓐㧁㸾∹慷(0.9 㚫⺢嬘⿍⿏ᷕ桐䘤ἄ3⮷㗪ℏᶼἧ䓐warfarin mg/Kg)䘬枸⼴㓰㝄Ἓ12ˤᶵㅱ╖䌐ẍˬ⸜漉 ᷳか侭炻劍INRʀ1.7炻⎗侫ㄖ㕥ㇻrt-PA烊 ⣏㕤80㬚˭㌺昌⿍⿏仢埨儎ᷕ桐䘬か侭忚埴 䘤ἄ⇵48⮷㗪ℏ㚦ἧ䓐Low Molecule Weight rt-PA㱣䗪炻ㅱ䵄⎰℞Ṿ㊯㧁 㔜橼姽Ộ炻 Heparinㆾ㚵䓐NOACᷳか侭炻ᶵ⺢嬘㕥ㇻ 嫡ヶἧ䓐ˤ 埨㞻㹞妋∹ˤỮ劍㚵䓐䘬㗗dabigatranᷳか 2.5 庽⽖ㆾ彭忇㓡┬䘬⿍⿏仢埨ᷕ桐か侭炻䴻姢 侭炻⎗侫ㄖἧ䓐⍵廱∹idarucizumab⼴ℵ㕥 㱣慓ⷓ⇌㕟⎰Ἕ㚱⣙傥䉨㱩炻ᶼ䃉䤩⽴䕯 ㇻrt-PA17ˤ劍㆟䔹㬌栆か侭㚱栙ℏLVO炻⎗ 㗪炻⎗侫ㄖ㕤ᷕ桐䘤ἄ3⮷㗪ℏ㕥ㇻ朄傰埨 侫ㄖ忚埴EVTˤ 㞻㹞妋∹(Class IIa, Level of Evidence A)ˤ 2.7 䔹Ụㆾ䡢姢 LVOᷳ⿍⿏仢埨⿏儎ᷕ桐か侭炻 㟡㒂䴙妰炻䲬40% NIHSS⮷㕤5䘬䕭か ⎗傥ㆾ⮯忚埴EVT⇵炻劍䫎⎰IVT㡅ẞ炻⎗ 㚱⣏埨䭉旣⠆(large vessel occlusion, LVO)炻 ⃰忚埴IVT㱣䗪(Class IIa, Level of Evidence 庽⽖ᷕ桐か侭ḇ⎗傥㚱⋲⼙⋨䘬⬀⛐13炻 B-R)ˤ 㬌栆䕭Ṣㅱ⎴㧋䴎Ḱ䧵㤝䘬㓹㱣ˤECASS ⎰ἝIVT⍲EVT䘬㧳㍍㱣䗪䘬⃒溆⊭ III䞼䨞憅⮵3-4.5⮷㗪庽⹎ᷕ桐䘬㫉㕷佌↮ ㊔⎗傥⛐埨㞻䦣昌⇵⶚䓙IVTㇻ忂埨䭉 㜸炻栗䣢ᷕ桐䦳⹎ᶵ⼙枧枸⼴冯sICH䘬㭼 (5-10%)炻ḇ⎗傥ἧEVT㚜≈⭡㖻炻ᶼ⌛ἧ ἳ14ˤ侴SITS-ISTR娎槿栗䣢炻NIHSS ≤ 5䘬 EVT㛒傥ㆸ≇ㇻ忂埨䭉ḇ傥㊩临ℵ㿴㳩㱣 庽⹎ᷕ桐か侭㕥ㇻrt-PA⛐0-3ㆾ3-4.5⮷㗪䘬 䗪烊仢溆䁢⎗傥⡆≈EVT㕥埴㗪儎↢埨䘬桐 mRS 0-1枸⼴䚠Ụ15ˤ 晒炻᷎ᶼ⎗傥⺞怚廱昊ㆾ⼙⁷⇘滈已悐䨧⇢ 2.6 ⿍⿏仢埨ᷕ桐䘤ἄ 3⮷㗪ℏ㚱ἧ䓐warfarin 㗪攻ˤ䞼䨞栗䣢炻⇵⽒䑘LVO䘬ᷕ桐䕭か⛐ ᷳか侭炻劍INR ≤ 1.7炻⎗侫ㄖ㕥ㇻ埨㞻㹞 ᷕ桐⼴6-8⮷㗪ℏ㍍⍿⎰ἝIVT⍲EVT炻㧳㍍ 妋∹(Class IIb, Level of Evidence B-R)ˤ⿍ 㱣䗪ᷳ䕭か⛐3ᾳ㚰䘬mRS 0-2㭼䌯䁢⮵䄏 ⿏仢埨ᷕ桐か侭⛐ᷕ桐䘤䓇⇵48⮷㗪㚦㚵 䳬䘬1.27᾵炻ᶼ䷥㬣ṉ䌯旵Ỷ役3ㆸ炻侴ℑ 䓐朆䵕䓇䳈K㊖㈿∹⎋㚵㈿ↅ埨∹(NOAC, 䳬䘬儎↢埨桐晒䚠役18ˤ⎘䀋儎ᷕ桐⬠㚫⺢ ⊭㊔dabigatranˣrivaroxabanˣapixabanˣ 嬘䔹Ụㆾ䡢姢LVOᷳ⿍⿏仢埨ᷕ桐か侭炻攳 edoxaban)炻ᶵ⺢嬘㕥ㇻ埨㞻㹞妋∹(Class ⥳㍍⍿IVT㗪炻⭄䚉⾓┇≽EVTᷳ姽Ộ冯⼴ III, Level of Evidence C-EO)ˤ侴㬌栆か侭劍 临㱣䗪炻ᶵ暨䫱⼭ㆾ奨⮇IVT䘬䗪㓰ˤ ㆟䔹㚱栙ℏLVO⎗侫ㄖ忚埴≽傰ℏ埨㞻䦣 㔜橼Ἦ婒炻⿍⿏仢埨ᷕ桐䕭Ṣ炻䘤ἄ㗪攻 昌埻(endovascular thrombectomy, EVT)(Class ⛐3-4.5⮷㗪ᶼ䃉䤩⽴䕯炻暨天⃀⾓㍍⍿IVT㱣

197 ijıIJĺԑĹТѕୢသϛॳᚖТོʼnŪŨũŭŪŨũŵ

䗪烊䘤ἄ㗪攻⛐4.5-9⮷㗪炻暨䓙慓䗪⛀昲ẍ娛 㚱栗叿䚠斄29ˤ㬌⢾炻ẍMRI↮㜸⿍⿏仢埨ᷕ 䳘䘬⼙⁷㩊㞍⋼≑炻惵⎰冐⸲䉨㱩Ἦ⇌㕟䕭Ṣ 桐䕭Ṣ䘬⋲⼙⋨⣏⮷炻䘤䎦儎悐LVO䘬䕭Ṣ炻 㗗⏎ㅱ㍍⍿IVT㱣䗪ˤ ⋲⼙⋨⎗⬀㳣攟忼9⮷㗪ẍᶲ30ˤ晾䃞1998⸜䘬 ECASS II娎槿31 ⍲2008⸜䘬EPITHET娎槿32 䃉㱽 ીՖϛॳӔៀࢺݽᕛ 嫱⮎ᷕ桐⼴3-6⮷㗪䴎ḰIVT㱣䗪⎗㓡┬枸⼴炻ܒĴįġġࡨ DEFUSE娎槿憅⮵⿍⿏仢埨ᷕ桐䘤ἄ3-6⮷㗪䘬 ـंܒएકޟ 䕭Ṣ忚埴MRI㿴㳩㓅⼙姽Ộ炻⮯䕭Ṣ↮ㆸ㚱⋲ ⎘ᷕ㥖㮹䷥慓昊䤆䴻慓⬠ᷕ⽫儎ᷕ桐ᷕ⽫ 昛㝷暾慓ⷓ ⼙⋨⍲㰺㚱⋲⼙⋨ℑ䳬炻䘤䎦㚱⋲⼙⋨䘬䕭Ṣ ㍍⍿IVT㱣䗪⼴炻ℵ㿴㳩ㆸ≇侭䚠庫㕤ℵ㿴㳩 ⋩⼙⋺သϛॳݽᕛᅋᡐ ⣙㓿侭炻㚱庫Ἓ䘬≇傥枸⼴炻军㕤㰺㚱ܒીՖܒĴįIJġࡨ 1995⸜䘬NINDS娎槿䡢䩳Ḯ朄傰rt-PA 䘬䕭Ṣ炻ℵ⹎ㆸ≇㿴㳩冯⏎᷎ᶵ⼙枧≇傥枸⼴ 㕤ᷕ桐⼴3⮷㗪㗪攻䨿䘬䗪㓰⼴19炻2008⸜䘬 33炻忁↮㜸ℵ⹎⻟婧Ḯ⋲⼙⋨㗗ℵ㿴㳩㱣䗪㓰 ECASS-III娎槿⇯⮯rt-PA䘬怑䓐㗪㨇㒜⯽军4.5 㝄䘬慵天⚈䳈炻⚈㬌EPITHET娎槿⮵㿴㳩ᶵ列 ⮷㗪8炻侴2015⸜⣏䆮䘤䘬EVT娎槿㼖䘬㬋⎹䳸 ⋨ῷ⎰(target mismatch)㍸↢㖶䡢䘬⭂佑炻⊭㊔ 㝄⇯⮯⿍⿏仢埨ᷕ桐ℵ㿴㳩㱣䗪⮶ℍḮℐ㕘䘬 㿴㳩㪲慵(perfusion-weighted imaging, PWI) / 㒜 昶㭝20-24炻啱≑檀昶⼙⁷↮㜸炻役Ḵ⸜㚜忚ᶨ㬍 㔋㪲慵(diffusion-weighted imaging, DWI)䘬橼䧵 ⮯ℵ㿴㳩㱣䗪䘬㗪攻䨿㍐⯽军24⮷㗪25, 26ˤ 㭼> 1.2炻␴PWI冯DWI䘬橼䧵ⶖ≥ 10㮓⋯34炻᷎ ẍ冒≽⼙⁷↮㜸庇橼(RAPID)ℵ㫉↮㜸炻䘤䎦 ીՖϛॳݽᕛϞࣺᜰधශ 㿴㳩ᶵ列⋨ῷ⎰䘬か侭㍍⍿IVT⼴炻58%㚱ܒĴįijġġࡨ ـं 㠿⠆㒜⣏(P = 0.046)炻䔞EPITHET冯DEFUSEẍ 8 2008⸜䘬ECASS-III娎槿栗䣢 炻仢埨ᷕ桐 䚠⎴䘬ῷ⎰⭂佑⎰Ἕ↮㜸⼴炻䘤䎦㚱ῷ⎰ᶼㆸ 䘤ἄ3-4.5⮷㗪ℏ䴎Ḱ朄傰rt-PA䘬䕭Ṣ炻䚠庫㕤 ≇㿴㳩侭⼿⇘列⤥枸⼴䘬⊅䬿㭼䁢㿴㳩⣙㓿䘬 ㍍⍿⬱ㄘ∹侭㚱㚜Ἓ䘬≇傥枸⼴(mRS 0-1)炻 5.61᾵炻军㕤㰺㚱ῷ⎰䘬䕭Ṣ炻ㆸ≇㿴㳩冯⏎ 㚱栗叿䴙妰シ佑ˤ忚ᶨ㬍↮㜸栗䣢炻ᷕ桐䘤ἄ ᷎ᶵ⼙枧≇傥枸⼴35ˤ ⼴3-4.5⮷㗪ℏ䴎Ḱrt-PA炻㭷䘦⎵か侭㚱16.4⎵ ⍿䙲炻侴㭷䘦Ṣᷕ2.7Ṣ⍿⭛27ˤ䴙⎰↮㜸栗 ĴįĴġņŗŕၐᡛᛖีዘ 䣢炻㕤ᷕ桐䘤ἄ3-4.5⮷㗪ℏ㍍⍿朄傰rt-PA㱣 晐叿IVT㱣䗪㖍㻠ㆸ䅇炻儎䳬䷼⼿⇘ㆸ≇ 䗪䘬䕭Ṣ炻㚱35.3%䕭Ṣ㚱列⤥䘬≇傥枸⼴炻 ℵ㿴㳩⮵ᷕ桐枸⼴䘬慵天⿏㻠⡆炻侴⍿䙲㕤ℵ

栗叿⃒㕤㍏⇞䳬(OR = 1.26炻95%CI = 1.05-1.51) 㿴㳩㱣䗪㚨⤥䘬䭬ἳ卓忶㕤⿍⿏⽫倴㠿⠆炻䃉 11 ˤ2018⸜伶⚳⽫冇⬠㚫⺢嬘⿍⿏仢埨ᷕ桐䘤 婾㗗ⅈ䉨≽傰㯋䎫㒜⻝埻ㆾ㓗㝞㱣䗪炻悥ᶨℵ ἄ3-4.5⮷㗪炻䫎⎰怑ㅱ䕯䘬䕭Ṣ炻IVTㅱ↿䁢 ㍸愺叿儎ᷕ桐⮰⭞⼨≽傰ℏ⮶䭉㱣䗪怩㬍䘬 5 䫔ᶨ䳂⺢嬘 ˤ 㕡⎹炻晾䃞䴻㬟ḮIMS-III36ˣSYNTHESIS37ˣ 晐叿忈⼙㈨埻䱦忚炻忶⼨ẍ儎ᷕ桐䘤ἄ㗪 MR RESCUE38 䘬⣙㓿炻⬠䓴ḇ䚳夳Ḯ⣙㓿䘬 攻 䁢IVT㱣䗪冯⏎䘬⇌㕟㧁㸾ḇ⍿⇘㊹㇘ˤ ⍇⚈炻ἳ⤪㍍⍿㱣䗪䘬䕭Ṣ㰺㚱栙ℏLVOˣἧ ẍMRI⮵⿍⿏仢埨ᷕ桐䕭Ṣ忚埴儎㿴㳩↮㜸炻 䓐冲✳䘬⍾㞻☐㡘ˣㆾ㰺㚱⮯⣏朊䧵㠿⠆↿ℍ 䘤䎦⌛ἧᷕ桐⼴24⮷㗪炻ṵ㚱䲬50%⋲⼙⋨ ㌺昌㡅ẞ䫱ˤ侴慵㕘姕妰⼴䘬Ḽ⣏娎槿⯙⁷ 28 ⬀㳣 炻ẍPET↮㜸ẋ嫅⍿㎵䘬仢埨儎䳬䷼䘤 㗗ᶨ⟜厗渿䘬䄁䀓⣏㇚炻㕤2015⸜䅫㓦⺽䆮炻 䎦炻⛐ᷕ桐䘤ἄ⼴48⮷㗪ℏṵ㚱悐ấ仢埨儎䳬 ⏠⺽Ḯ⣏⭞䘬䚖⃱炻晐㨇娎槿MR CLEAN20ˣ ䷼⬀㳣炻ᶼ⬀㳣䳬䷼䘬Ỽ䌯冯ᷕ桐♜慵⹎嬲⊾ ESCAPE21ˣEXTEND-IA22ˣSWIFT PRIME23

198 ijıIJĺԑĹТѕୢသϛॳᚖТོʼnŪŨũŭŪŨũŵ

冯REVASCAT24 栗䣢⛐怑䔞䘬㡅ẞ怠㑯ᶳ炻 EVT㱣䗪᷎ᶵ㚫⡆≈sICH䘬桐晒(OR = 1.03炻 EVT冯╖䲼ἧ䓐IVT䚠㭼庫炻㚱庫⤥䘬≇傥枸 p = 0.88)41ˤ⚈㬌䕭Ṣ䨞䪇天㍍⍿IVTˣEVTㆾ ⼴炻ᶼᶵ㚫⡆≈儎↢埨桐晒ˤ㩊夾忁Ḽ⣏娎 ℑ侭⎰Ἕ㱣䗪炻⽭枰⯙ᾳ⇍ね㱩侫慷㱣䗪㕡 槿䘬䲵ℍ㧁㸾炻栙ℏLVO㗗⽭天㡅ẞ炻ᷕ桐♜ 㱽炻IVT冯EVTℑ侭攻᷎㰺㚱䪞䇕斄Ὢ炻军㕤 慵⹎(NIHSS慷堐)䘬天㯪⇯Ḻ㚱ⶖ䔘烉SWIFT ⎴㗪䫎⎰IVT⍲EVT怑ㅱ䕯䘬䕭Ṣ㗗⏎⎗䚜㍍ PRIME (8-29↮)炻ᶱᾳ娎槿㰺㚱NIHSS慷堐ᶲ ➟埴EVT侴㌐⍣IVT炻⇯㚱⼭㛒Ἦ娎槿䘬妋䫼 旸(MR CLEAN ≥ 2炻ESCAPE > 5炻REVASCAT > (SWIFT DIRECTˣMR CLEAN NO IV)ˤ 6)炻EXTEND-IA⇯㰺㚱天㯪NIHSS慷堐㧁㸾炻 㚱ᶱᾳ娎槿⮯ASPECT慷堐↿ℍ㧁㸾(ESCAPE ĴįĶġņŗŕᎌᔖ੿ޟᘗ৤ 6-10炻SWIFT-PRIME 7-10炻REVASCAT 㖊䃞5⣏娎槿䡢䩳ḮEVT⛐⿍⿏仢埨ᷕ 7-10)炻Ḵᾳ娎槿天㯪儎㿴㳩忈⼙㠿⠆橼䧵⮷ 桐䘬奺刚炻⬫㗗⏎傥㒜⯽ㅱ䓐㚜⣂䕭Ṣ烎 㕤70㮓⋯ᶼ⬀⛐ῷ⎰⋨(EXTEND-IAˣSWIFT- DEFUSE-2娎槿䘬㫉↮㜸䞼䨞㊯↢42炻ẍMRI PRIME)炻䳸㝄栗䣢EVT⮵㕤栙ℏLVO忼⇘ℵ 栗䣢㚱㿴㳩ῷ⎰䘬䕭Ṣ炻⤪ㆸ≇䴻≽傰ℏ㱣䗪 忂䌯(TICI 2b/3)䘬㭼䌯䲬6-9ㆸ炻ᶼ列⤥枸⼴ 侴ℵ㿴㳩侭炻℞列⤥≇傥枸⼴䘬㭼䌯栗叿⡆≈ (mRS 0-2)䘬㭼䌯忼33-71%炻⮯ᷕ桐䘤ἄ㗪攻䲵 (OR = 4.0炻p = 0.02)炻ᶼᶵ⍿旸㕤䘤䕭军㱣䗪㗪 ℍ㧁㸾⭂䁢4.5⮷㗪ℏ䘬EXTEND-IA冯SWIFT 攻㗗⏎⣏㕤ㆾ⮷㕤6⮷㗪(p = 0.56)ˤ⚈㬌䚠庫 PRIME娎槿䘬列⤥枸⼴㭼䌯庫Ἓ炻↮⇍㗗60% 㕤㗪攻䨿(time window)炻ẍ䳬䷼䨿(tissue-based ⍲71%烊䴙⎰↮㜸栗䣢39炻㍍⍿EVT䳬忼⇘列⤥ window)Ἦ䮑怠䕭Ṣ炻⎗ẍἧ㚜⣂⿍⿏仢埨ᷕ 枸⼴䘬㭼䌯䁢46%炻㍏⇞䳬䁢26% (OR = 1.7炻 桐䕭Ṣ⍿䙲㕤EVTˤ2018⸜䘬DAWN娎槿26 憅 p < 0.0001)炻⎬㫉↮䳬↮㜸⊭⏓⸜漉ˣASPECT ⮵6-24⮷㗪ℏ䘤䕭䘬⇵儎⽒䑘LVOˣNIHSS ≥10 ↮㔠ˣ㗗⏎⎰Ἕ朄傰rt-PAˣNIHSS慷堐ˣ䘤䕭 ↮䘬䕭Ṣ炻⤪ᷕ桐♜慵⹎冯㠿⠆橼䧵㚱ῷ⎰䎦 军EVT㗪攻ˣ⍲⿏⇍䫱炻⛯ᶨ农⿏⛘㊯↢EVT 尉㗪炻晐㨇↮惵军EVTㆾ喍䈑㱣䗪炻㚨⼴䚖㑲 䘬⤥嗽炻㚱⸜漉< 50㬚ˣASPECT > 6↮⍲ 㬋ⷠ军㍍⍿㱣䗪䘬ᷕỵ㔠㗪攻䲬12⮷㗪炻℞ᷕ NIHSS < 10↮䘬㕷佌㰺㚱栗叿ⶖ䔘炻⎎⢾sICH 㚱63%䕭Ṣ䁢䜉愺㗪ᷕ桐(wake-up stroke)炻䳸 䘬㭼䌯4.4%炻冯㍏⇞䳬㰺㚱栗叿ⶖ䔘ˤ⎎ᶨ 㝄栗䣢EVT䳬㚱庫檀㭼䌯䘬列⤥≇傥枸⼴(49% 䲣䴙⿏↮㜸栗䣢炻グ㖑忚埴EVT冯IVT炻℞枸 㭼13%)炻ᶼℑ䳬攻䘬sICH㰺㚱栗叿ⶖ䔘ˤ䵲 ⼴㓰㝄グἛ40ˤ㟡㒂REVASCAT24 屯㕁㇨忚埴 ㍍侭䘤堐䘬DEFUSE-3娎槿25 ⇯憅⮵6-16⮷㗪ℏ 䘬㗪攻庠冯枸⼴↮㜸炻䘤䎦冒䘤䕭军➟埴EVT 䘤䕭ˣ⇵儎⽒䑘LVOˣ㠿⠆橼䧵< 70㮓⋯ˣ㿴 㗪攻㭷⡆≈30↮揀炻⯙㚫㷃⮹5%⽑⍇列⤥䘬⎗ 㳩ῷ⎰㭼≥ 1.8ˣᶼῷ⎰橼䧵≥ 15㮓⋯䘬䕭Ṣ炻 傥⿏炻℞ᷕ⼙枧庫⣏䘬㗗⬴ㆸCT军➟埴EVT㗪 晐㨇↮惵军EVTㆾ喍䈑㱣䗪炻ᷕ桐䘤ἄ军㍍⍿ 攻炻㭷⡆≈30↮揀炻⯙㚫㷃⮹17%⽑⍇列⤥䘬 㱣䗪䘬ᷕỵ㔠㗪攻䲬11ᾳ⮷㗪炻℞ᷕ㚱50%䕭 ⎗傥⿏炻⚈㬌㓡┬昊ℏ㳩䦳㗗⼰慵天䘬婚柴ˤ Ṣ䁢䜉愺㗪ᷕ桐炻䳸㝄栗䣢EVT䳬㚱庫檀㭼 䌯䘬列⤥≇傥枸⼴(OR = 2.67炻p < 0.001)炻ᶼ ĴįĵġņŗŕᇄŊŗŕޟᜰ߽ ℑ䳬䘬sICH㰺㚱栗叿ⶖ䔘ˤ䳸⎰ESCAPE21ˣ EVT冯IVTᷳ攻㗗⎰ἄ㈹ㆾ㗗䪞䇕斄Ὢ烎 REVASCAT24ˣDEFUSE-325⍲DAWN26 䘬䴙⎰ 䴙⎰↮㜸栗䣢炻䃉婾䕭Ṣ㗗⏎㚱㕥ㇻ朄傰rt- ↮㜸䞼䨞43炻䘤䎦ᷕ桐⼴崭忶6⮷㗪䘬䕭Ṣ㕤㍍ PA炻䫎⎰EVT怑ㅱ䕯ᶼ㍍⍿㱣䗪䘬䕭Ṣ䘬列 ⍿EVT⼴炻列⤥枸⼴䘬⊅䬿㭼㗗喍䈑䳬䘬3.33 ⤥枸⼴㗗㰺㚱㱣䗪侭䘬䲬2.5᾵ 39ˤ⎎ᶨ䴙⎰ ᾵炻ᶼsICH㰺㚱栗叿⡆≈ˤ伶⚳⽫冇⬠㚫㊯⺽ ↮㜸栗䣢炻䚠庫㕤㚨Ἓ⊾䘬喍䈑㱣䗪炻⎰Ἕ ⶚⮯6-16⮷㗪ℏᷕ桐䘬EVT↿䁢class I䘬㱣䗪⺢

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嬘炻侴16-24⮷㗪䘬㱣䗪⺢嬘䁢IIa5ˤ ĴįĹġ๖ġ፣

ኇ៪ IVT怑ㅱ䕯姽Ộ烉䔞䕭Ṣᷕ桐䘤䓇㗪攻⮷ޟĴįķġ໌໦ኇ჋ᄇŊŗŕݽᕛ 䃉䌐㚱„炻⋲⼙⋨ㆾ㿴㳩ῷ⎰䘬㤪⾝ḇἧ 㕤4.5⮷㗪炻ㅱ忚埴朄傰rt-PA怑ㅱ䕯姽Ộ烊劍䘤 ⼿IVT䘬㗪攻䨿⼿Ḱ⺞攟炻WAKE-UP娎槿2 ⇑ 䓇㗪攻䁢4.5-9⮷㗪ㆾᷕ桐㗪攻㛒䞍炻⇯⽭枰德 䓐MRI㩊㷔儎ᷕ桐䘤䓇㗪攻⣏㕤4.5⮷㗪ˣᶼ㚱 忶忈⼙㈨埻䡢娵㗗⏎䫎⎰⋲⼙⋨ㆾ㿴㳩ῷ⎰⭂ DWI-FLAIRῷ⎰䘬䕭Ṣ晐㨇↮惵军㍍⍿IVT㱣 佑炻⍫侫WAKE-UP␴EXTEND娎槿䘬㡅ẞ炻᷎ 䗪ㆾ㧁㸾喍䈑㱣䗪炻℞ᷕ㚱崭忶90%䕭Ṣ㗗䜉 侫慷娚慓昊姕⁁⍲Ṣ≃⼴炻㰢⭂㗗⏎忚埴朄傰 愺㗪ᷕ桐炻ᶼ冒㚨⼴䚖㑲㬋ⷠ军㍍⍿㱣䗪䘬ᷕ 㹞㞻㱣䗪ˤ ỵ㔠㗪攻⣏䲬㗗10⮷㗪炻IVT㱣䗪䳬䘬列⤥枸 EVT怑ㅱ䕯姽Ộ烉劍䕭Ṣᷕ桐䘤䓇㗪攻⮷ ⼴㭼䌯㖶栗⃒㕤㍏⇞䳬(53.3%㭼41.8%炻OR = 㕤6⮷㗪炻⎗⍫侫伶⚳⽫冇⬠㚫㊯⺽㇨↿䫎⎰䫔 1.61炻p = 0.02)炻sICH㭼䌯䃉栗叿ⶖ䔘(8.0%㭼 ᶨ䳂⺢嬘䘬㡅ẞ⍲⎬⛘⋨冒妪䘬⍫侫夷䭬炻军 4.9%炻OR = 1.78炻p = 0.13)ˤ⎎ᶨ⮶ℍ䳬䷼䨿 㕤ᶵ䫎⎰䫔ᶨ䳂⺢嬘㡅ẞ䘬䕭Ṣ炻ㅱ⯙慓昊姕 㤪⾝䘬娎槿㗗EXTEND3炻⬫⮯NIHSS 4-26↮ˣ ⁁ˣṢ≃⍲䕭Ṣ䈡⿏䁢ᾳ⇍侫慷炻㰢⭂㗗⏎➟ 㗪攻䨿㗗4.5军9⮷㗪ˣ㚱㿴㳩ῷ⎰䘬⿍⿏仢埨 埴EVT炻军㕤䘤䕭㗪攻6-24⮷㗪䘬䕭Ṣ炻⎗⍫ ᷕ桐䕭Ṣ晐㨇↮惵军朄傰rt-PAㆾ⬱ㄘ∹炻侴㿴 侫DAWN␴DEFUSE-3䘬䲵ℍ⍲㌺昌㡅ẞ炻⍲ 㳩ῷ⎰䘬⭂佑㗗ῷ⎰㭼> 1.2ˣῷ⎰橼䧵> 10㮓 ⎬⛘⋨䚠斄夷䭬⍲䕭Ṣ䈡⿏ ᾳ⇍侫慷炻ẍ㰢 ⋯ᶼ㠿⠆橼䧵ᶵ⣏㕤70㮓⋯炻65%䘬䕭Ṣ㗗䜉 ⭂㗗⏎➟埴EVTˤ 愺㗪ᷕ桐炻℞ᷕ䲬70%䕭Ṣ㚱栙ℏLVO炻䳸㝄 ⿍⿏仢埨ᷕ桐ℵ㿴㳩㱣䗪䘬怠㑯⍲➟埴㗪 栗䣢㍍⍿朄傰rt-PA䳬㚱列⤥枸⼴䘬㭼䌯栗叿檀 㨇㗗ᶨ攨喅埻炻慓ⷓ侫慷⼿ᶵ㗗娚ᶵ娚忚埴 㕤⬱ㄘ∹䳬炻ᶼ24⮷⼴䘬埨䭉ℵ忂㭼䌯栗叿庫 ℵ㿴㳩炻ḇ天侫慷慓昊傥ᶵ傥➟埴㱣䗪炻⍲䕭 檀炻ỮsICH䔍檀㕤⬱ㄘ∹䳬ˤ Ṣ㚫ᶵ㚫⚈㬌⍿䙲炻忁⊭⏓Ḯ䕭Ṣˣ⭞Ⱄ⍲䣦 㚫䫱⣂慵奨溆䘬侫慷炻ῤ⼿㶙⿅ˤ ᎌᔖ੿ޟĴįĸġņŗŕݽᕛ 晾䃞伶⚳⽫冇⬠㚫㊯⺽⶚㖶䡢㊯↢䫎⎰ᶳ ୤ՃМᝦ ↿㡅ẞ䘬⿍⿏仢埨ᷕ桐䕭Ṣㅱ㍍⍿EVT㱣䗪(⺢ 嬘䫱䳂䁢I)5烉(1) 䘤䕭⇵mRS 0-1↮烊(2) ℏ柠≽ 1. Whiteley WN, Emberson J, Lees KR, et 傰ㆾᷕ⣏儎≽傰(middle cerebral artery, MCA)䫔 al. Risk of intracerebral haemorrhage with ᶨ㭝旣⠆烊(3) ⸜䲨ʁ18㬚烊(4) NIHSSʁ6↮烊 alteplase after acute ischaemic stroke: a (5) ASPECTSʁ6↮烊(6) 䘤䕭6⮷㗪ℏ㍍⍿EVT secondary analysis of an individual patient data 㱣䗪ˤỮ㗗冐⸲ᶲ䴻ⷠ㚫忯⇘ᶨ䳂⺢嬘夷䭬⢾ meta-analysis. Lancet Neurol 2016;15:925-933. 䘬䕭Ṣ炻ἳ⤪怈䪗MCA旣⠆ˣASPECT < 6↮ˣ 2. Thomalla G, Simonsen CZ, Boutitie F, et al. 㠿⠆䭬⚵> 1/3䘬MCA㿴㳩⋨䫱ˤ䴙⎰↮㜸䘤䎦 MRI-guided thrombolysis for stroke with MCA䫔Ḵ㭝旣⠆䘬䕭Ṣ⤪㍍⍿EVTṵ㚱庫檀㭼 unknown time of onset. N Engl J Med 2018; 䌯䘬列⤥枸⼴44炻ASPECT 3-5↮ㆾ㠿⠆䭬⚵⣏ 379:611-622. 㕤1/3䘬MCA㿴㳩朊䧵䘬䕭Ṣ㍍⍿EVTḇ㚱庫Ἓ 3. Ma H, Campbell BCV, Parsons MW, et al. 䘬列⤥枸⼴45ˤ⚈㬌ᶨ䳂⺢嬘夷䭬⢾䘬䕭Ṣ㗗⏎ Thrombolysis guided by perfusion imaging up ⎗㍍⍿EVT炻暨天㚜忚ᶨ㬍䘬娎槿炻ḇ天侫慷 to 9 hours after onset of stroke. N Engl J Med 慓昊姕⁁ˣ㈨埻傥≃⍲䕭Ṣ䈡⿏䫱ᾳ⇍侫慷ˤ 2019;380:1795-1803.

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4. Hsieh FI, Lien LM, Chen ST, et al. Get with randomized trials. Int J Stroke 2018;13:175- the Guidelines-Stroke performance indicators: 189. surveillance of stroke care in the Taiwan Stroke 11. Chen YW, Sung SF, Chen CH, et al. Intravenous Registry: Get with the Guidelines-Stroke in thrombolysis administration 3-4.5 h after acute Taiwan. Circulation 2010;122:1116-1123. ischemic stroke: a retrospective, multicenter 5. Powers WJ, Rabinstein AA, Ackerson T, et al. study. Front Neurol 2019;10:1038. American Heart Association Stroke Council. 12. Chao AC, Hsu HY, Chung CP, et al. Outcomes 2018 Guidelines for the early management of thrombolytic therapy for acute ischemic of patients with acute ischemic stroke: A stroke in Chinese patients: the Taiwan guideline for healthcare professionals from the Thrombolytic Therapy for Acute Ischemic American Heart Association/American Stroke Stroke (TTT-AIS) study. Stroke 2010;41:885- Association. Stroke 2018;49:e46-e110. 890. 6. Chen CH, Hsieh HC, Sung SF, et al. 2019 13. Shryock JC, Belardinelli L. Inhibition of Taiwan Stroke Society Guideline for late sodium current to reduce electrical intravenous thrombolysis in acute ischemic and mechanical dysfunction of ischaemic stroke patients. Formos J Stroke 2019;1:1-22. myocardium. Br J Pharmacol 2008;153:1128- 7. Lees KR, Bluhmki E, von Kummer R, et al. 1132. Time to treatment with intravenous alteplase 14. Bluhmki E, Chamorro A, Dávalos A, et al. and outcome in stroke: an updated pooled Stroke treatment with alteplase given 3.0-4.5 h analysis of ECASS, ATLANTIS, NINDS, and after onset of acute ischaemic stroke (ECASS EPITHET trials. Lancet 2010;375:1695-1703. III): additional outcomes and subgroup analysis 8. Hacke W, Kaste M, Bluhmki E, et al. of a randomised controlled trial. Lancet Neurol Thrombolysis with alteplase 3 to 4.5 hours 2009;8:1095-1102. after acute ischemic stroke. N Engl J Med 15. Ahmed N, Wahlgren N, Grond M, et al. 2008;359:1317-1329. Implementation and outcome of thrombolysis 9. Emberson J, Lees KR, Lyden P, et al. Stroke with alteplase 3-4.5 h after an acute stroke: Thrombolysis Trialists’ Collaborative an updated analysis from SITS-ISTR. Lancet Group. Effect of treatment delay, age, and Neurol 2010;9:866-874. stroke severity on the effects of intravenous 16. Tang SC, Tsai LK, Yeh SJ, et al. Secular trends thrombolysis with alteplase for acute ischaemic of stroke subtypes in Taiwan; National Taiwan stroke: a meta-analysis of individual patient University Hospital Stroke Registry, 1995- data from randomised trials. Lancet 2014;384: 2018. Formos J Stroke 2019;1:50-60. 1929-1935. 17. Pollack CV Jr, Reilly PA, van Ryn J, et al. 10. Hacke W, Lyden P, Emberson J, et al. Stroke Idarucizumab for dabigatran reversal - full Thrombolysis Trialists’ Collaborators Group. cohort analysis. N Engl J Med 2017;377:431- Effects of alteplase for acute stroke according 441. to criteria defining the European Union and 18. Mistry EA, Mistry AM, Nakawah MO, et al. United States marketing authorizations: Mechanical thrombectomy outcomes with and Individual-patient-data meta-analysis of without intravenous thrombolysis in stroke

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patients: a meta-analysis. Stroke 2017;48:2450- Stroke 2009;40:2433-2437. 2456. 28. Darby DG, Barber PA, Gerraty RP, et al. 19. National Institute of Neurological Disorders Pathophysiological topography of acute and Stroke rt-PA Stroke Study Group. Tissue ischemia by combined diffusion-weighted and plasminogen activator for acute ischemic perfusion MRI. Stroke 1999;30:2043-2052. stroke. N Engl J Med 1995;333:1581-1587. 29. Markus R, Reutens DC, Kazui S, et al. Hypoxic 20. Berkhemer OA, Fransen PS, Beumer D, et al. tissue in ischaemic stroke: persistence and A randomized trial of intraarterial treatment clinical consequences of spontaneous survival. for acute ischemic stroke. N Engl J Med 2015; Brain 2004;127:1427-1436. 372:11-20. 30. Copen WA, Rezai Gharai L, Barak ER, et al. 21. Goyal M, Demchuk AM, Menon BK, et al. Existence of the diffusion-perfusion mismatch Randomized assessment of rapid endovascular within 24 hours after onset of acute stroke: treatment of ischemic stroke. N Engl J Med dependence on proximal arterial occlusion. 2015;372:1019-1030. Radiology 2009;250:878-886. 22. Campbell BC, Mitchell PJ, Kleinig TJ, et al. 31. Hacke W, Kaste M, Fieschi C, et al. Randomised Endovascular therapy for ischemic stroke with double-blind placebo-controlled trial of perfusion-imaging selection. N Engl J Med thrombolytic therapy with intravenous alteplase 2015;372:1009-1018. in acute ischaemic stroke (ECASS II). Second 23. Saver JL, Goyal M, Bonafe A, et al. Stent- European-Australasian Acute Stroke Study retriever thrombectomy after intravenous t-PA Investigators. Lancet 1998;352:1245-1251. vs. t-PA alone in stroke. N Engl J Med 2015; 32. Davis SM, Donnan GA, Parsons MW, et al. 372:2285-2295. Effects of alteplase beyond 3 h after stroke 24. Jovin TG, Chamorro A, Cobo E, et al. in the Echoplanar Imaging Thrombolytic Thrombectomy within 8 hours after symptom Evaluation Trial (EPITHET): a placebo- onset in ischemic stroke. N Engl J Med 2015; controlled randomised trial. Lancet Neurol 372:2296-2306. 2008;7:299-309. 25. Albers GW, Marks MP, Kemp S, et al. 33. Albers GW, Thijs VN, Wechsler L, et al. Thrombectomy for stroke at 6 to 16 hours with Magnetic resonance imaging profiles predict selection by perfusion imaging. N Engl J Med clinical response to early reperfusion: the 2018;378:708-718. diffusion and perfusion imaging evaluation 26. Nogueira RG, Jadhav AP, Haussen DC, et al. for understanding stroke evolution (DEFUSE) Thrombectomy 6 to 24 hours after stroke with study. Ann Neurol 2006;60:508-517. a mismatch between deficit and infarct. N Engl 34. Nagakane Y, Christensen S, Brekenfeld C, et J Med 2018;378:11-21. al. EPITHET: positive result after reanalysis 27. Saver JL, Gornbein J, Grotta J, et al. Number using baseline diffusion-weighted imaging/ needed to treat to benefit and to harm for perfusion-weighted imaging co-registration. intravenous tissue plasminogen activator Stroke 2011;42:59-64. therapy in the 3- to 4.5-hour window: joint 35. Lansberg MG, Lee J, Christensen S, et al. outcome table analysis of the ECASS 3 trial. RAPID automated patient selection for

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reperfusion therapy: a pooled analysis of the al. A systematic review and meta-analysis of Echoplanar Imaging Thrombolytic Evaluation randomized controlled trials of endovascular Trial (EPITHET) and the Diffusion and thrombectomy compared with best medical Perfusion Imaging Evaluation for Understanding treatment for acute ischemic stroke. Int J Stroke Stroke Evolution (DEFUSE) Study. Stroke 2015;10:1168-1178. 2011;42:1608-1614. 42. Lansberg MG, Cereda CW, Mlynash M, et al. 36. Broderick JP, Palesch YY, Demchuk AM, et al. Response to endovascular reperfusion is not Endovascular therapy after intravenous t-PA time-dependent in patients with salvageable versus t-PA alone for stroke. N Engl J Med tissue. Neurology 2015;85:708-714. 2013;368:893-903. 43. Vidale S, Longoni M, Valvassori L, Agostoni 37. Ciccone A, Valvassori L, Nichelatti M, et al. E. Mechanical thrombectomy in strokes with Endovascular treatment for acute ischemic large-vessel occlusion beyond 6 hours: a stroke. N Engl J Med 2013;368:904-913. pooled analysis of randomized trials. J Clin 38. Kidwell CS, Jahan R, Gornbein J, et al. A Neurol 2018;14:407-412. trial of imaging selection and endovascular 44. Menon BK, Hill MD, Davalos A, et al. treatment for ischemic stroke. N Engl J Med Efficacy of endovascular thrombectomy in 2013;368:914-923. patients with M2 segment middle cerebral 39. Goyal M, Menon BK, van Zwam WH, et al. artery occlusions: meta-analysis of data from Endovascular thrombectomy after large-vessel the HERMES Collaboration. J Neurointerv ischaemic stroke: a meta-analysis of individual Surg 2019;11:1065-1069. patient data from five randomised trials. Lancet 45. Roman LS, Menon BK, Blasco J, et al. 2016;387:1723-1731. Imaging features and safety and efficacy of 40. Prabhakaran S, Ruff I, Bernstein RA. Acute endovascular stroke treatment: a meta-analysis stroke intervention: a systematic review. JAMA of individual patient-level data. Lancet Neurol 2015;313:1451-1462. 2018;17:895-904. 41. Balami JS, Sutherland BA, Edmunds LD, et

203 204 Endovascular Treatment Workshop

11/22 Fri. ◰侐敞⺁ W5 Time Topic Speaker Moderator Professor of Neurology, Dual Antiplatelet therapy in Introduction溪⽌䬸 憒⸒ 14:30-15:00 Inje University, Korea acute ischemic stroke Discussion㜵⻡⾞ 憒⸒ Keun-Sik Hong 15:00-15:10 Opening 㤱⬷峉 憒⸒ Treatment strategy for acute 15:10-15:50 occlusion in symptomatic 䥶⻡䛨㼚ⷅⷩ憒晉 Introduction 欶媇Ἰ 憒⸒ (40 min) intracranial arteriosclerotic 晚㕮ἀ 㕀㍯ Discussion 晚╆Ẩ 憒⸒ stenosis 15:50-16:05 Ḕ⛲昫憒 Introduction ≰ⳮ䥌 憒⸒ Learning and Case Sharing (1) (15 min) 溪噠䑃 憒⸒ Discussion ⼜⁌⭶ 憒⸒ 16:05-16:20 ⽗㿘䦧ₚ Introduction 欶媇Ἰ 憒⸒ Learning and Case Sharing (2) (15 min) 晚凛曽 憒⸒ Discussion 晚㕮ἀ 憒⸒ ぐḢ⅓ Introduction ⭒䑃 憒⸒ 16:20-16:35 Learning and Case Sharing (3) 㜘㵞䑅 憒⸒ Discussion 唈K暫 憒⸒ ⛲㳗憒晉 Introduction 晚╆Ẩ 憒⸒ 16:35-16:50 Learning and Case Sharing (4) 晚⎯◰ 憒⸒ Discussion 晚╆Ẩ 憒⸒ 16:50-17:00 Panel discussion 晚╆Ẩ 憒⸒

Stroke territories, mimics, and chameleons Case Report

11/22 Fri. 俷㖖䍲⬷棖⹾ W5 Time Topic Speaker Moderator Mapping the Supratentorial Cerebral Professor of Neurology, 18:30-18:50 Arterial Territories Using 1160 Large Dongguk University, Korea Artery Infarcts Dong-Eog Kim 凡Ḕ㦕两 18:50-19:00 Discussion 晚㞶曽 憒⸒ 凡⌾㖗㧺 19:00-19:10 Stroke mimics and chameleons 嬄掕晤 憒⸒ ◰侐⟡䝊㕀 Vertigo and posterior circulation 凡Ḕㄯ㿆 ⭲㗮Ⳗ 憒⸒ 19:10-19:30 stroke ⼜㺲⛪ 憒⸒ 凡⌾㖗㧺 Case reports 19:30-20:45 6䴫 嬄掕晤 憒⸒ (㮶䴫⠘␱10⇭揿˚姵媽2⇭揿) 20:45-21:00 Discussion and Conclusion All

205 11/23 (SAT.) 08:00-18:00 ◰侐⟡䝊㕀憒晉 (08:00-08:30 娢ⅱ⠘∗)

㈛⾞㣕⛲暂㛪字⻚

EMS˚telestroke˚triage˚stroke team -㈛⾞㣕⛲暂㛪字⻚ TIME TOPIC SPEAKER MODERATOR Acute stroke treatment network 檿暫ⷩ㵯昙Ⱗ 08:30-08:45 and pre-hospital management in 㝾㔦⯓ 䦸Ⓢ Kaohsiung ᷰ两憒晉 Acute stroke treatment network and 㜵ᾱ㳗 憒⸒ 㖗⋾ⷩ㵯昙Ⱗ 08:45-09:00 pre-hospital management in New 檿⭾䥡 䦸敞 Taipei City Telestrokeăexperience of ⽗⋽⟡䝊 Ἰ㯸憒晉 09:00-09:20 Changhua Christian Hospital ⭒䨭ṥ 憒⸒ ⷒ挒曽 晉敞 檿暫敞⺁ 檿暫敞⺁ 09:20-09:40 Triaging patients with acute stroke 㴑⣒⼞ 憒⸒ ⼜尞ⷅ 憒⸒ 曀⑳憒晉 曀⑳憒晉 09:40-10:00 Comprehensive Stroke Center 晚潴 憒⸒ 僈㜄㦕 憒⸒ 10:00-10:30 Coffee Break

IVT & EVT -㈛⾞㣕⛲暂㛪字⻚ TIME TOPIC SPEAKER MODERATOR Professor of Reperfusion therapy for acute Neurology, Inje ⏗䁊免Ḕ梏⭟㛪 10:30-11:00 ischemic stroke in Korea University, Korea 愔⻡凯 䏭Ṳ敞 Keun-Sik Hong Vice President of National Cerebral Extending therapeutic time window 檿憒昫晉 11:00-11:30 and Cardiovascular for acute reperfusion therapy 㝾䑅㳗 憒⸒ Center, Japan Kazunori Toyoda 11:30-11:40 Discussion Under the guidelines or beyond that Ḕ⛲昫憒 Ḕ⛲昫憒 11:40-12:00 Case discussion 溪噠䑃 憒⸒ ≰ⳮ䥌 憒⸒ Kaohsiung-Pinton Collaborative 晚Ẽ庹 娘᷽‰ Endovascular Therapy for Acute 嬄㝘栋 ⼜尞ⷅ 曀⑳憒晉 12:00-12:20 Ischemic Stroke 檿敞ⰶ㝘䶱「 晚╆Ẩ 憒⸒ (堧㟺䧢晋檿敞ⰶ㝘⌧⟆⏯ὃ䵺樾) 免Ḕ梏㲢䘩⛿晱 12:20-12:30 Discussion 13:30-14:00 ⢨⠘媽㕮姵媽 (⢨⠘媽㕮⌧)

206 PAC & Long-term care -㈛⾞㣕⛲暂㛪字⻚ TIME TOPIC SPEAKER MODERATOR

◰侐ⷩ 14:00-14:10 OPENING 溪㔶デⷩ敞 ⽗⋽⟡䝊 檿暫敞⺁ 14:10-14:35 「『⽳㜆䅎孞⛇ㆰ䬽䕌 䍲㕮䔒 憒⸒ ⼜尞ⷅ 憒⸒ 凡⋾㦕两 旃㸈憒晉 14:35-15:00 免Ḕ梏「『⽳㜆䅎孞ㇷ㞃⇭Ẓ 溪啀䐍 孞䏭⸒ 晚㗳㗵 憒⸒ ◰侐ⷩ塂䔆Ⱗ ◰侐⟡䝊 15:00-15:20 敞䅎⭬「ᾦă◰侐䵺樾 ⼜俧ㆲ Ⱗ敞 ⧁䶔Ẩ 晉敞 ⽗⋽䦧ₚ 偖㖗⛲暂 凡⌾㖗㧺 15:20-15:30 Panel Discussion 欶媇Ἰ 憒⸒ 晚⏚䷖ 憒⸒ 嬄掕晤 憒⸒ 15:30-15:50 Coffee Break Professor of Neurology and Associate Dean BP Targets in Secondary Stroke at University of ⏗䁊免Ḕ梏⭟㛪 15:50-16:30 Prevention: Does One Size Fit All? California, San 愔⻡凯 䏭Ṳ敞 Francisco, USA

Bruce Ovbiagele

16:30-17:30 ℑ䦧媽㕮䙣塏 17:30-18:00 㛪Ⓢ⤎㛪

207 11/23 (SAT.) 08:00-18:00 ◰侐⟡䝊㕀憒晉 (08:00-08:30 娢ⅱ⠘∗)

䬓ṳ嬂⟩ vascular dementia & small vessel diseases -䬓ṳ嬂⟩(㮶栳18⇭揿: 15⇭揿㻻嬂, 3⇭揿姵媽)

TIME TOPIC SPEAKER MODERATOR

CADASIL in Taiwan: an update and 08:30-08:48 凡⋾㦕两 凡⋾㦕两 future perspectives ⺽侱䬸 憒⸒ 捥办叴 憒⸒

Cerebral amyloid angiopathy: an 08:48-09:06 凡⤎憒晉 曀⑳憒晉 update and future perspectives 唈㬊䆠 憒⸒ 僈㜄㦕 憒⸒

Small vessel disease and geriatric 09:06-09:24 檿暫昫憒 䫌䶃⏯憒晉 syndrome 㝾䦧劓 憒⸒ 娘⻿㮬 憒⸒

BBB & glymphatic system in 09:24-09:42 凡⋾憒⤎ dementia 㤱⾾屑 ⊐䏭㕀㍯ 吓劚憒晉 晚㘰媣 憒⸒ Biomarkers of vascular cognitive 09:42-10:00 檿暫敞⺁ impairment 溪╆䶔 憒⸒

10:00-10:30 Coffee Break

ICH˚SAH˚neurosurgery -䬓ṳ嬂⟩

TIME TOPIC SPEAKER MODERATOR

10:30-11:00 Hemorrhagic stroke - SAH, ICH ◰侐⟡䝊 晚㘘屑 憒⸒ ◰侐⟡䝊 唈⭾Ἰ 憒⸒ Hemorrhagic stroke - Surgical 11:00-11:30 ◰侐⟡䝊 treatment ⭒䑅㗵 憒⸒

Consensus Guidelines for the 11:30-12:00 Medical Treatment of Spontaneous ᷰ两憒晉 ᷰ两憒晉

Intracerebral Hemorrhage ⑏Ḕ凯 憒⸒ 㜵ᾱ㳗 憒⸒

Consensus Guidelines for the 12:00-12:30 Surgical Treatment of Spontaneous ᷰ两憒晉 凡⋾㦕两

Intracerebral Hemorrhage 㹖⅝㚥 憒⸒ Ợ㣕∐ 憒⸒

13:30-14:00 ⢨⠘媽㕮姵媽 (⢨⠘媽㕮⌧)

208 Oral Papers (young scholars) -䬓ṳ嬂⟩ TIME TOPIC ⠘␱俬 偞㥔憒晉 MODERATOR 13:30-14:00 ⢨⠘媽㕮姵媽 (⢨⠘媽㕮⌧) 㜘㰟廰 凡⤎憒晉

㜘㵞䑅 ぐḢ⅓憒晉 檿暫昫憒 ⭲䢎⦴ ㇷ⤎昫憒 嶀暬䐛 憒⸒

晚⾾㗱 凡⤎憒晉 凡⋾㦕两 娘䪲⤮ 憒⸒ ₚ῕ 凡⤎憒晉 ◰侐敞⺁ 14:20-15:50 ⢨⠘媽㕮⏊栔⠘␱ 㛥⬷功 凡⋾㦕两 㜵⭆ 憒⸒ ≰㿆⻿ 㝾⏊敞⺁ 凡⤎憒晉 唈❋䑲 凡⤎㖗䫠 㹖柳␂ 憒⸒

唈㬊䆠 凡⤎⋾孞 ㌖凯憒晉 峛总㗳 憒⸒ 欶暬䑐 檿暫⛲庴

(㋰䬭䕒柭⹶)

209 11/24 (SUN.) 08:00-18:00 ◰侐⟡䝊㕀憒晉 (08:00-08:30 娢ⅱ⠘∗)

㈛⾞㣕⛲暂㛪字⻚

AF/PFO detection and treatment-㈛⾞㣕⛲暂㛪字⻚ TIME TOPIC SPEAKER MODERATOR

ESUS: Who and What with 凡⋾㦕两 凡Ḕ㽫㷬 09:00-09:25 diagnosis 㜵〈ㅎ 憒⸒ 吰⭯㭊 憒⸒ 凡⤎憒晉 榓‼憒晉 09:25-09:50 ESUS: How and When in treatment 唈⊂⇘ 憒⸒ 䶔Ẩ 憒⸒ 㖗ℰ憒晉 09:50-10:00 Panel Discussion 怊䪲㗵憒⸒ 10:00-10:30 Coffee Break

凡⋾㦕两 檿暫昫憒 10:30-10:55 Cardiac rhythm monitoring in ESUS 嶀⬷⇈ 憒⸒ 㝾⭾㆙ 憒⸒ 檿暫敞⺁ 檿暫昫憒 10:55-11:20 Cardiac imaging in ESUS 晚㰟晭 憒⸒ 㝾⭾㆙ 憒⸒ PFO: current management and 凡⤎憒晉 凡⤎憒晉 11:20-11:45 prospectives 㝾承㳗 憒⸒ 愔⻡凯 憒⸒ 檿暫昫憒 11:45-11:55 Panel Discussion 㝾⭾㆙ 憒⸒

210 11/24 (SUN.) 08:00-18:00 ◰侐⟡䝊㕀憒晉 (08:00-08:30 娢ⅱ⠘∗)

䬓ṳ嬂⟩

Imaging of Acute Stroke -䬓ṳ嬂⟩ TIME TOPIC SPEAKER MODERATOR Cerebral Small Vessel Disease ◰侐敞⺁ 凡⋾㦕两 08:30-08:50 - Beyond White Matter 唈K暫 憒⸒ 佬ℭ⯝ 憒⸒ Hyperintensities What should we do next in EVT for AIS? The real world years ⤮併憒晉 ㌖凯憒晉 08:50-09:10 after BIG5: Experience of single ⳻䤷⟪ 憒⸒ 愎㜏䁒 憒⸒ institution Mechanical Thrombectomy for ⽗⋽⟡䝊 09:10-09:30 acute stoke: experience sharing of 晚⧨剖 憒⸒ CCH ⤮併憒晉 ⳻䤷⟪ 憒⸒ 劘哕ㄯ㿆 09:30-09:50 Irradiated carotid stenosis 昕您῕ 憒⸒ 09:50-10:00 Q & A 10:00-10:30 Coffee Break

AI in medicine -䬓ṳ嬂⟩ TIME TOPIC SPEAKER MODERATOR

ὦ䔏㷘⺍⭟侹㖣免㳉姱噆⇭桅凮免㳉 Ḕ⤕曢㩆ⷌ䧲㈧ 凡⋾㦕两 10:30-10:50 ạ㩆Ẳ杉廻⅞ 㜵㞶䢱 㕀㍯ 㜵〈ㅎ 憒⸒ ⯵⅌ạⷌ㙡ㅎ⇭㝷 憶⋽ῲạ免⯶堧 凡⤎曢㩆䳢 曀⑳憒晉 10:50-11:10 䮈䖥䖬岇㒻 㜵⮃こ ⍁⣒ 晚╆Ẩ 憒⸒ ㆰ䔏ạⷌ㙡ㅎ㉧堺㖣㪉樾岮㖀-⌻⊐ 敞⺁⤎⭟岮䮈䳢 11:10-11:30 减⹱㱡䬽 㛥ヶ⃹ 㕀㍯ Ḕ㭊岮姱䮈䏭⭟䳢 Ḕ㭊岮ⷌ㈧ 僈暬㶜 㕀㍯ 11:30-11:50 免惏堧䮈ᷰ䶔憴⻡㉧堺 㝾䶔㙿 㕀㍯ 11:50-12:00 Discussion

⤎㛪㙁⮛-◰侐俷㖖䍲⬷棖⹾ 18:30-20:30 䏭Ṳ敞凛婅 柹䌵 㑟⽐ (㛪Ⓢ塏㻻)

211 ⹛㛪岛岺㻻嬂

Plenary Lecture

BP Targets in Secondary Stroke Prevention: Does One Size Fit All? Bruce Ovbiagele, MD, MSc, MAS, MBA Associate Dean of the San Francisco VA Healthcare System Professor of Neurology, University of California, San Francisco     [          System

Dr. Ovbiagele earned his MD from the University of Lagos, Master of Science in Clinical Research (MSc) from UCLA, Master of Advanced Studies (MAS) from UCSD, MBA from the University of Massachusetts, Amherst, and an Executive Certificate in Public Leadership from the John F. Kennedy School of Government at Harvard University. Dr. Ovbiagele maintains several National Insititutes of Health funded research programs, focused on improving outcomes for those with, or at risk for stroke, including the largest study of stroke in Sub-Saharan Africa, to-date. In 2008, his work was recognized by the American Academy of Neurology with the Michael Pessin Stroke Research Leadership Award. Dr. Ovbiagele is an elected fellow of the Royal College of Physicians (London), American Academy of Neurology, American Neurological Association, American Heart Association Stroke Council, American Association of Physician Leadership, and European Stroke Organization, as well as an AAMC Council of Deans Fellow. He is also the immediate past chair of       !       [           National Spokesperson for the American Stroke Association, interpreting the latest stroke science for medical professionals and the lay public.

Abstract While the underlying pathophysiological rationale and clinical trial evidence for lowering blood pressure (BP) in people with hypertension to safely and effectively prevent a primary stroke of any type are overwhelmingly clear, there remain unresolved questions with regard to secondary stroke prevention - what to do, when to do it, with whom to do it, and how aggressively to do it? Concerning the last question, a relative lack of clarity persists due to   [                  relative paucity of published BP target secondary stroke prevention treatment trials, especially aims at systolic BP targets < 120 mmHg. This presentation will provide an overview of prevailing published evidence from limited clinical trial data, observational studies, and meta- analyses; review current expert consensus guideline recommendations; examination emerging insights from recently published and soon-to-be published studies; and finally convey the notion that at this time a differential approach to BP Targets in Secondary Stroke Prevention may be required for certain stroke patient populations.

212 ℑ䦧媽㕮䌵

ijıIJĺġԑᓺؾ፣МዩுዩӪ൐

ѮᢊသϛॳᏰོᓺؾ፣Мዩ ᙽឍᚂᏰ᜸੫ᓺǺጰݒᐫᙴৣȐᆵεᙴଣȑܖஅᙃ ፕdzЎǺMicroangiopathy underlying mixed-location intracerebral hemorrhages/microbleeds: A PiB-PET study. Neurology 2019;92(8):e1–e8.

ᚂᏰ᜸੫ᓺǺ݅ݒሺᖏ׉ᛰৣȐᆵεᙴଣȑחᖝ ፕdzЎǺ Real World Rivaroxaban and Apixaban Levels in Asian Patients with Atrial Fibrillation. Clinical Pharmacology and Therapeutics 2019 Aug 2. doi: 10.1002/ cpt.1601. ᓺ้Ǻ੍݅ϘᙴৣȐᆵчᄪᕴȑ ፕdzЎǺ Noninferiority Margins in Trials of Thrombectomy Devices for Acute Ischemic StrokeǺIs the Bar Being Set Too Low? Stroke. 2019 Oct 17 ȑ܌زᓺ้Ǻഋ⍌ཁȐ໚ܴεᏢғ౛Ꮲࣴ ፕdzЎǺ Aryl Hydrocarbon Receptor Modulates Stroke-induced Astrogliosis and Neurogenesis in the Adult Mouse Brain. Journal of Neuroinflammation 2019;16:187.

Рཱིक܈፣Мዩ (ᙴৣ(ཥчѱҥᖄӝᙴଣܷۏளዛΓǺ݅ ፕdzЎǺ Perioperative/Postoperative Atrial Fibrillation and Risk of Subsequent Stroke and/or Mortality A Meta-Analysis. Stroke. 2019;50:1364–1371.

သՖᆓ੽੾٩ݽஅߜོଽَ݂ఀ௲ᓺؾ፣Мዩ ಃ΋ӜǺᖙႨᏂᙴৣȐᆵεᙴଣȑ ፕdzЎǺ Early Recurrent Stroke in Patients Receiving Mechanical Thrombectomy. Poster presentation ಃΒӜǺ೚ਕ᝿ᙴৣȐ޸ጪཁᔮȑ ፕdzЎǺ Long-term stroke incidence in proximal thoracic aortic dissection survivors: a nationwide population-based cohort study.

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ـϞသഋωՖᆓ੾ᡐȈ᜸ᐦ઱ғυីኇϞंޱ౅ӫ࠮သюՖ௉ 4ǵ׵࢙ߙ4ǵ෯Ⴈ։2ǵPanagiotis Fotiadis3ǵ໳ఃએ5ǵޱጰݒᐫ1, 2ǵMarco Pasi3ǵጰΚഩ2ǵഋ໡ ᚑऩޱ6ǵᎄࡌᑫ2ǵEdip Gurol3 1Ѡεᙴଣчៈϩଣઓ࿶ϣࣽ 2Ѡεᙴଣઓ࿶ϣࣽ ύЈز3ऍ୯ഞԀᕴᙴଣတрՈࣴ 4ѠεᙴଣቹႽᙴᏢࣽ 5ѠεᙴଣЈ᠌ϣࣽ 6ѠεᙴଣਡηᙴᏢࣽᄤ҅ηឪቹύЈ

Microangiopathy Underlying Mixed-location Intracerebral Hemorrhages/ Microbleeds: A PiB-PET Study Hsin-Hsi Tsai1, 2, Marco Pasi3, Li-Kai Tsai2, Ya-Fang Chen4, Bo-Ching Lee4, Sung-Chun Tang2, Panagiotis Fotiadis3, Chen-Yu Huang5, Ruoh-Fang Yen6, Jiann-Shing Jeng2, M. Edip Gurol3 1 Departments of Neurology, National Taiwan University Hospital Bei-Hu Branch, Taipei, Taiwan 2 Departments of Neurology, National Taiwan University Hospital, Taipei, Taiwan 3 Hemorrhagic Stroke Research Program, Department of Neurology, Massachusetts General Hospital Stroke Research Center, Harvard Medical School, Boston, MA, USA 4 Department of Medical Imaging, National Taiwan University Hospital, Taipei, Taiwan 5 Division of Cardiology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan 6 Department of Nuclear Medicine, National Taiwan University Hospital, Taipei, Taiwan

Objective: To test the hypothesis that patients with concomitant lobar and deep intracerebral hemorrhages/microbleeds (mixed ICH) have predominantly hypertensive small vessel disease (HTN-SVD) rather than cerebral amyloid angiopathy (CAA), using in vivo amyloid imaging. Methods: Eighty Asian patients with primary ICH without dementia were included in this cross-sectional study. All patients underwent brain MRI and 11C-Pittsburgh compound B (PiB)-PET imaging. The mean cortical standardized uptake value ratio (SUVR) was calculated using cerebellum as reference. Forty-six patients (57.5%) had mixed ICH. Their demographic and clinical profile as well as amyloid deposition patterns were compared to those of 13 patients with CAA-ICH and 21 patients with strictly deep microbleeds and ICH (HTN-ICH). Results: Patients with mixed ICH were younger (62.8 ± 11.7 vs 73.3 ± 11.9 years in CAA, p = 0.006) and showed a higher rate of hypertension than patients with CAA-ICH (p < 0.001). Patients with mixed ICH had lower PiB SUVR than patients with CAA (1.06 [1.01–1.13] vs 1.43 [1.06–1.58], p = 0.003). In a multivariable logistic regression model, mixed ICH was     "  $\^^`{ [   | }\M`$\‚\‚ƒ„   † ‡ ˆ‰Š"  ‚\‚‹^`{ [   | ‚\‚‚}M‚\$Œ‚\‚„   to CAA after adjustment for age. Compared to HTN-ICH, mixed ICH showed a similar   "ƒ\$/}}\Œ|‚\}/}\`  ’•–—!’„     [ " ˜‚\}„\ Furthermore, PiB SUVR did not differ between mixed ICH (values presented above) and HTN-ICH (1.10 [1.00–1.16], p = 0.45). Conclusions: Patients with mixed ICH have much lower amyloid load than patients with CAA-ICH, while being similar to HTN-ICH. Overall, mixed ICH is probably caused by HTN- ‰™    [      |  \

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ᡊᆰᠬଢ଼ఊတϞᐨ࡙ϷݙܘࢸЖٳRivaroxabanᇄapixabanܻ ர4ǵ໳ᙃ޹1, 2ǵ෯Ⴈ։3ǵᎄࡌᑫ3قݒሺ1, 2ǵ೾ᒸᐇ2ǵယធൈ3ǵጰΚഩ3ǵቅ݅ 1ѠεᙴଣᛰᏊ೽ س2Ѡ᡼εᏢᛰᏢ஑཰ᏢଣᛰᏢ 3Ѡεᙴଣઓ࿶೽တύ॥ύЈ 4Ѡεᙴଣϣࣽ೽ЈՈᆅύЈ

Real World Rivaroxaban and Apixaban Levels in Asian Patients with Atrial Fibrillation Shin-Yi Lin, MS1, 2; Ching-Hua Kuo, PhD2; Shin-Joe Yeh, MD PhD3; Li-Kai Tsai MD, PhD3; Yen-Bin Liu, MD, PhD4; Chih-Fen Huang, PhD1, 2; Sung-Chun Tang, MD, PhD3; Jiann-Shing Jeng, MD, PhD3 1 Department of Pharmacy, National Taiwan University Hospital, Taipei, Taiwan. 2 School of Pharmacy, College of Medicine, National Taiwan University, Taipei, Taiwan. 3 Stroke Center and Department of Neurology, National Taiwan University Hospital, Taipei, Taiwan. 4 Department of Internal Medicine, Cardiovascular Center and Division of Cardiology, National Taiwan University Hospital, Taipei, Taiwan.

Introduction: Although the therapeutic index for non-vitamin K antagonist oral anticoagulants (NOAC) is wide, measuring NOAC level remains the most arbitrary method for evaluating the pharmacologic effect. The study aims to measure the plasma levels of rivaroxaban and  š   ›   [  "›œ„        š  drug levels from clinical studies. Methods: AF patients aged more than 20 years who took rivaroxaban or apixaban for more than 7 days were enrolled. Peak and trough levels were collected at 1-4 hours after medication ingestion and right before the next dose, respectively. Samples were measured using ultra-high performance liquid chromatography with tandem mass spectrometry. Results: A total of 178 patients were enrolled, 73 who took rivaroxaban (15 mg daily, 34 patients; 10 mg daily, 39 patients) and 105 who took apixaban (5 mg twice daily, 44 patients; 2.5 mg twice daily, 61 patients). Patients in the apixaban group were more likely to be ordered an inappropriately-adjusted dose compared to those in the rivaroxaban group (37.5% versus 22.5%, p = 0.046). The percentage of those with drug levels within the expected          [       š      rivaroxaban group, both for trough (84.8% versus 64.4%, p = 0.002) and peak level (76.9% versus 33.8%, p < 0.001). After adjusting for age, sex, kidney function, appropriate dose and adherence, patients in the rivaroxaban group were still less likely to have peak and trough levels within the expected drug levels (odds ratio [OR] for trough 0.279, 95% confidence interval [CI] = 0.13–0.62, P = 0.002; for peak, OR = 0.172, 95% CI = 0.08–0.35, P < 0.001). Conclusion: Our real world data suggests that Asian patients taking rivaroxaban are more likely to have out-of-expected drug levels than those taking apixaban.

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ᖝࣨ঄Ϟ௤ଆܒ੃ၐᡛϞߨӛڥသϛॳܒીՖܒࡨ ੍݅Ϙ1ǵJeffrey L. Saver2 1ᆵчᄪ҇ᕴᙴଣ 2ऍ୯уԀεᏢࢶ׼ᕚϩਠ

Noninferiority Margins in Trials of Thrombectomy Devices for Acute Ischemic Stroke : Is the Bar Being Set Too Low? Chun-Jen Lin1, Chun-Jen Lin2 1 Division of Cerebrovascular Diseases, Neurological Institute, Taipei Veterans General Hospital, Taiwan 2 Comprehensive Stroke Center and Department of Neurology, David Geffen School of Medicine, University of California, Los Angeles, USA

Background and Purpose: Novel endovascular thrombectomy (EVT) devices for acute ischemic stroke are often cleared by regulatory agencies on the basis of noninferiority trials. The relation between the noninferiority margins used in trials and the minimal clinically important differences (MCIDs) determined by experts have not been systematically investigated. Methods: Systematic searches were performed to identify (1) all noninferiority design or noninferiority-presented stroke-EVT trials for acute ischemic stroke, (2) all studies determining the MCIDs for the same outcomes, and (3) all noninferiority coronary revascularization trials. Stroke-EVT trial results were reanalyzed using the broad noninferiority margins originally used and narrower noninferiority margins derived from formal MCID studies. Results: We identified 7 noninferiority-designed or noninferiority-interpreted stroke-EVT controlled trials, enrolling 1766 patients, variously comparing coil retrievers, first- and second-generation stent retrievers, and aspiration devices. In 6 trials, the primary outcome was achievement of reperfusion, using noninferiority margins of 15% (3 trials), 10% (2 trials), and ${"} „\    š  |  [!™     ‹\}{ 5%, and cardiac trials used noninferiority margins of 3.5% to 4.4%. In one stroke-EVT trial, the primary outcome was functional independence, using a noninferiority margin of 15%. However, 2 stroke expert survey studies identified MCIDs for functional independence as having lower values, 5% and 1% to 1.5%. For both reperfusion and functional independence outcomes, all 7 trials demonstrated noninferiority with the broadest noninferiority margin, but only 4 and 3 trials demonstrated noninferiority with actual expert-derived margins for reperfusion and functional independence, respectively. Conclusions: Noninferiority margins used in EVT device trials have regularly exceeded the MCIDs determined by stroke experts, as well as margins used for cardiac devices. New approaches, such as the use of reasonably adequate performance margins, rather than noninferiority margins, are needed to optimize stroke-EVT trial design integrity and trial performance feasibility.

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ᇄડငཱིҡއသϛॳࡣϞડငีܒᡝ፡࿽ԙჃࡨڧ≏޿ॷ ች2, 3, 7܃ဖ1, 3ǵ׵܃6ǵ׵דഋ⍌ཁ1ǵ஭ҥ㗟2ǵ໳࣬ᅺ4ǵ໳ࢅണ1ǵԣࡾጪ5ǵ೾Ớ ܌ز1໚ܴεᏢғ౛Ꮲࣴ ܌ز2໚ܴεᏢတࣽᏢࣴ ύЈز3໚ܴεᏢတࣽᏢࣴ ᛰ౛Ꮲࣽس 4ύξᙴᏢεᏢᙴᏢ 5ਁᑫᙴଣ ଣزᏢࣴނଣಒझᆶঁᡏғز6ύѧࣴ 7Ѡчᄪᕴઓ࿶ᙴᏢύЈတՈᆅࣽ Aryl Hydrocarbon Receptor Modulates Stroke-induced Astrogliosis and Neurogenesis in the Adult Mouse Brain Wan-Ci Chen1, Li-Hsin Chang2, Shiang-Suo Huang4, Yu-Jie Huang1, Chun-Lien Chih5, Hung-Chih Kuo6, Yi-Hsuan Lee1, 3, I-Hui Lee2, 3, 7 1 Department and Institute of Physiology, National Yang-Ming University, Taipei, Taiwan. 2 Institute of Brain Science, National Yang-Ming University, Taipei, Taiwan. 3 Brain Research Center, National Yang-Ming University, Taipei, Taiwan. 4 Department of Pharmacology, Institute of Medicine, Chung-Shan Medical University, Taichung, Taiwan. 5 Cheng Hsin General Hospital, Taipei, Taiwan. 6 Stem Cell Program, Institute of Cellular and Organismic Biology, Academia Sinica, Taipei, Taiwan. 7 Division of Cerebrovascular Diseases, Neurological Institute, Taipei Veterans General Hospital, Taipei, Taiwan.

Background: The aryl hydrocarbon receptor (AHR) is a ligand-dependent transcription factor activated by environmental agonists and dietary tryptophan metabolites for the immune response and cell cycle regulation. Emerging evidence suggests that AHR activation after acute stroke may play a role in brain ischemic injury. However, whether AHR activation alters poststroke astrogliosis and neurogenesis remains unknown. Methods: We adopted conditional knockout of AHR from nestin-expressing neural stem/ progenitor cells (AHRcKO) and wild-type (WT) mice in the permanent middle cerebral artery occlusion (MCAO) model. WT mice were treated with either vehicle or the AHR antagonist ƒaa— š\ |"•œ` „    \•    š   at 2 and 7 days after MCAO. Results •›’Š       [       \‡•œ— treated WT and AHRcKO mice showed significantly decreased infarct volume, improved sensorimotor, and nonspatial working memory functions compared with their respective controls. AHR immunoreactivities were increased predominantly in activated microglia and astrocytes after MCAO compared with the normal WT controls. The TMF-treated WT and AHRcKO mice demonstrated significant amelioration of astrogliosis and microgliosis. Interestingly, these mice also showed augmentation of neural progenitor cell proliferation at the ipsilesional neurogenic subventricular zone (SVZ) and the hippocampal subgranular zone. At the peri-infarct cortex, the ipsilesional SVZ/striatum, and the hippocampus, both the TMF-    ›’Š ¡¢    £—}!£—œ–—"!¦!£}  }‚‚!        –  ƒ –  }\ Conclusion –   — [ ›’Š  |             astrogliosis and suppressed neurogenesis in adult mice. AHR inhibition in acute stroke may  [           \       preserving neurogenesis.

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ᠬଢ଼ᇄࡣ៉ϛॳЅԫιॳᓎȈࡣ೩ϷݙܘЙ೚ࠉࡣю౪ϞЖ 1ǵBruce Ovbiagele5ۏ࣓4ǵ׵ە1ǵHooman KamelǵDaniel E. Singer3ǵֆܷۏ݅ 1჏ကߏ۪ᙴଣઓ࿶೽ 2Department of Neurology, Weill Cornell Medical College, New York. 3 Division of General Internal Medicine, Massachusetts General Hospital and Harvard Medical School, Boston. ܌زଣဂᡏ଼நࣽᏢࣴز4୯ৎፁғࣴ 5Department of Neurology, University of California, San Francisco.

Perioperative/Postoperative Atrial Fibrillation and Risk of Subsequent Stroke and/or Mortality A Meta-Analysis Meng-Hsin Lin, MD1; Hooman Kamel, MD2; Daniel E. Singer, MD3; Yi-Ling Wu, DrPH4; Meng Lee, MD1; Bruce Ovbiagele, MD, MS5 1 From the Department of Neurology, Chang Gung University College of Medicine, Chang Gung Memorial Hospital, Chiayi, Taiwan 2Department of Neurology, Weill Cornell Medical College, New York. 3 Division of General Internal Medicine, Massachusetts General Hospital and Harvard Medical School, Boston. 4Institute of Population Health Sciences, National Health Research Institutes, Miaoli County, Taiwan. 5Department of Neurology, University of California, San Francisco.

Background and Purpose: Although believed to be transient and self-limiting, new-    |  |  [  "†¢›œ„        and mortality. We conducted a systematic review and meta-analysis to qualitatively and quantitatively evaluate the relationship of POAF with early and late risks of mortality and stroke. Methods: We searched Pubmed, EMBASE, and Cochrane Library (1966 through March 2018) to identify cohort studies that reported stroke and mortality associated with POAF. We computed a random-effects estimate based on the Mantel- Haenszel method. Odds ratios with 95% CI were used as a measure of the association between POAF and early (in- hospital or within 30 days of surgery) stroke and mortality, while hazard ratios (HR) were used for long- term outcomes. Results: Our analysis included 35 studies with 2 458 010 patients. Pooling the results from the random-effects model showed that POAF was associated with increased risks of early stroke (odds ratio, 1.62; 95% CI, 1.47–1.80), early mortality (odds ratios, 1.44; 95% CI, 1.11–1.88), long-term stroke (HR, 1.37; 95% CI, 1.07–1.77), and long-term mortality (HR, 1.37; 95% CI, 1.27–1.49). Analyses focusing on high-quality studies obtained similar results. In subgroup analyses, POAF was more strongly associated with stroke in patients undergoing noncardiac surgery (HR, 2.00; 95% CI, 1.70–2.35) than in patients undergoing cardiac surgery (HR, 1.20; 95% CI, 1.07–1.34). Conclusions: New-onset POAF is associated with an increased risk of stroke and mortality, both in the short-term and long- term. The best strategy to reduce stroke risk among these patients needs to be determined.

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௤ଆחᖝޟϛॳܒ੃೚ࡣ฻෈ϱӔีીՖڥᐠడ ᖙႨᏂ1, 3ǵ׵஖ᆢ2ǵ෯Ⴈ։1ǵᎄࡌᑫ1 1ᆵεᙴଣઓ࿶೽ 2ᆵεᙴଣቹႽᙴᏢ೽ 3ᆵεᙴଣ໦݅ϩଣઓ࿶೽

Early Recurrent Stroke in Patients Receiving Mechanical Thrombectomy Sung-Ju Hsueh1, 3, Chung-Wei Lee2, Sung-Chun Tang1, Jiann-Shing Jeng1 1Department of Neurology, National Taiwan University Hospital, Taiwan. 2Department of Radiology, National Taiwan University Hospital, Taiwan. 3Department of Neurology, National Taiwan University Hospital Yun-Lin Branch, Taiwan.

Background: Mechanical thrombectomy for acute ischemic stroke is a proven technique effective in selective patients. This study described the incidence and clinical characteristics of early recurrent stroke (ERS) in patients receiving mechanical thrombectomy from a single center in Taiwan. Methods: We retrospectively reviewed patients who had acute ischemic stroke and received mechanical thrombectomy from January 2015 to September 2018 at National Taiwan University Hospital. ERS was defined as newly developed neurological deficit localized a different vascular territory and not caused by hemorrhage within the 21 days after the onset of š \§     [  [Š   0ƒ ‹ after stroke. Results: During the period, 200 patients (mean age 71.62 ± 12.34 years, male 49.0%) received mechanical thrombectomy. 17 patients (mean age 65.0 ± 15.54 years, male 35.3%) developed ERS (8.50%, 95% confidence interval 5.39- 13.39%.) The stroke etiologies of those with ERS were cardioembolism in 10 (58.8%) patients, active cancer with positive disseminated intravascular coagulation profiles in 4 patients (23.5%), catastrophic antiphospholipid syndrome in 1 (5.9%) patient, and large artery atherosclerosis in 2 (11.8%) patients. 10 (58.8%) of them received repeated mechanical thrombectomy, all achieving successful revascularization and none developed symptomatic hemorrhage. The patients with and without ERS had comparable good functional outcome (29.4% versus 41.0%, p = 0.31). Conclusion: ESR in stroke patients with mechanical thrombectomy was not rare, and repeated mechanical thrombectomy could be effective and feasible in subjects with ERS.

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ߖᆒкଢ଼૕থᚔ௉ޱޟߝ෈သϛॳีҡ౥ ೚ਕ᝿1ǵቅӼٖ1, 2ǵ᝵༝ඵ3, 4ǵᎄЎҥ1,5 1޸ጪཁᔮᙴଣઓ࿶ϣࣽ س2ཁᔮεᏢᙴᏢ 3ύ୯ᙴᛰεᏢᙴᏢଣ 4ύ୯ᙴᛰεᏢεኧᏵύЈ ᐒᄬز5ऍ୯уԀεᏢᙑߎξϩਠӄౚတ଼நࣴ

Long-term stroke incidence in proximal thoracic aortic dissection survivors: a nationwide population-based cohort study Jin-Yi Hsu1, An-Bang Liu1, 2, Yuan-Chih Su3, 4 and Boon Lead Tee1, 5 1 Buddhist Tzu Chi General Hospital, Department of Neurology, Hualien, Taiwan R.O.C.; 2 Buddhist Tzu Chi University, Department of Medicine, Hualien, Taiwan R.O.C.; 3         ![   "  #  $ # % &'''( 4 China Medical University, College of Medicine, Taichung, Taiwan R.O.C.; 5 Global Brain health institute, Atlantic Fellows for Equity in Brain Health, San Francisco, USA

Background: Proximal thoracic aorta dissection (pTAD) is a fatal disease, but the advancement in surgical repair technique increase overall survival rate. Studies have demonstrated that there are increase perioperative risk for stroke incidence after pTAD surgery. However, there lacks evidence illustrating the long-term stroke incidence in pTAD individuals, that impact the long-term morbidity, mortality, and usage of antithrombotic agents. Method: Using Taiwan National Health Insurance Research Database (NHIRD), a nationwide population-based cohort, we recruited 3,501 pTAD survivors hospitalized from January 1st, 2000 to December 31th, 2012. To ensure study cohort quality, only patients that underwent aortic dissection repair surgery and age 20 and above are included. The control cohort is  [       "       „  }     the use of propensity score. The primary outcomes include ischemic stroke and intracranial hemorrhage incidence 30 days after surgery. Results: Compared to the control cohort, pTAD survivor had higher risk for intracranial hemorrhage (adjusted hazard ratio [aHR]: 2.09; 95% confidence interval [CI]: 1.57–2.78), ischemic risk (aHR:1.82; 95%CI: 1.55–2.14). Risk factors for intracranial hemorrhage include middle age (45-64 year-old) and dyslipidemia and risk factors for ischemic stroke include young age (<45 year-old) and chronic kidney disease. Conclusion: Despite surviving the acute aortic dissection and surgical repair surgery, our study suggests that pTAD patients may still face an increased risk of intracranial hemorrhage and ischemic stroke in the future. Further research and guideline are warranted to prevent such occurrence.

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ijıIJĺġԑོᏩൢ፣М

No ፣МӪᆎȃհޱ οᓞ ൢ֙ 1 ຀ЇჴᏯတ೽Ћೌ Ⲗځ෯ တύ॥ Ɉ܄ᐟჹᄌڈࢬႝޔ಍ӝϩ݋௖૸࿶ᢅکӣ៝܄಍س΋ҽPRISMA 2 ஻ޣ΢ަфૈ܄ࡠൺޑቹៜ ǵླྀ۸ػے᚟໡ዝǵ೚ᝬ ᖏ׉௖૸ޑတύ॥܄ਵೌࡕԐයӆวલՈڗᐒఓ 3 ǵ݅ࡏՎǵጰΚഩǵ׵஖ᆢǵ෯Ⴈ։ǵᎄࡌᑫܸדᖙႨᏂǵഋ ᠼᆢ᠞୏௼ဂϐᐚࡋϩ݋܊٥ࢪЈܭRivaroxabanᆶapixaban 4 ரǵ໳ᙃ޹ǵ෯Ⴈ։ǵᎄࡌᑫقݒሺǵ೾ᒸᐇǵယធൈǵጰΚഩǵቅ݅ زቹៜǺ΋ҽ಍ӝϩ݋ࣴޑޣတύ॥ॴӸܭᐟჹڈࢬႝޔ࿶ᢅ 5 ǵഋ᜼Бے᚟໡ዝǵ೚ᝬ 6 ՈύNfLᆶGFAPёႣෳCADASILϐ੯ੰᝄख़ࡋϷύ॥ൺว Ɉ ǵ෯Ⴈ։ǵᎄࡌᑫܸדഋ ൔ֋ٯບᘐഐٝǺ΋ੰޑᓍ୏ે-ੇᆟᝠ➷ᆅܭᢅՈᆅຬॣݢჹ 7 ഋ࢙Ӽǵ݅╈൛ ൔ֋ٯংဂᔕ՟ᓍ෎ઓ࿶ਥੰᡂǺ΋ੰੱسတ༸ύ॥ੰ஻և౜ϣୁᒙ 8 ᗛइ୻ ᖏࣚॶϐ௖૸܄ਵ၂ᡍϐߚӍڗတύ॥܄લՈ܄࡚ 9 ੍݅ϘǵJeffrey Saver ቹៜޑύ॥ੰΓܭ᏾ӝࣽᖄӝྣៈჹکઓ࿶ࣽ 10 ଯകǵ݅ችীǵ׵ྷนǵ೚ࡌమǵླ੍ྀሎ݅ 11 ୏ેϣՈਵ౽ନೌࡕวғੱރ܄တрՈϐ॥ᓀຑ՗ Ɉ ǵ෯Ⴈ։ǵᎄࡌᑫۏǵ݅։፣ǵ׵ܸדഡ໺অǵഋ 12 Ѡऍύ॥ฦᒵύࡼѺՈਵྋှᏊੰ஻ϐКၨ ǵഋҏ๭ǵᎄࡌᑫǵ೚ख़ကǵणඦࡹܸדഋ 13 ණӧ܄ୃᡛୃᓐภϐวբයᆶόวբයޑ҅ηᘐቫ೷ቹКၨ ࢙݅՘ǵ൹৪໋ǵЀ३ҏ ݤѲྷМੱǵଯાữለՈੱϷယለલЮวғϸᙟύ॥Ǻٳӝ܄تԃᇸ 14 ൔ֋ٯ΋ਢ ՙڂդࢅǵ݅݅ Ь୏୏ેዦϐ܄গᚆٳύ॥ӝ܄લՈ܄΋Տ࡚ܭᓉેՈਵྋှᏊ٬Ҕ 15 ੰΓ ᖴᙼ໚

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16 ࡚܄લՈύ॥୏ેϣՈਵ౽ନೌࡕϐᡉቹᏊတੰᡂ Ɉ ǵ׵஖ᆢǵጰΚഩǵ෯Ⴈ։ǵᎄࡌᑫܸדԙ҉ၩǵഋ ൔ֋ٯύ॥ϐᏉՈ䁙চ୷ӢཥँᡂF2 p.F382Lਢ܄рՈٳတᓉેਵ༞ 17 ች܃ຐဖǵ஭Κ㗟ǵᗛ߀๩ǵ׵݅ ӈൔ֋ Ɉسٯ౽ନೌǺੰڗတύ॥୏ેՈ܄࿶ާ୏ે຾ՉલՈ 18 ԙੇྷǵ݅ࡏՎǵ෯Ⴈ։ǵ׵஖ᆢ ઓ࿶༸ಒझ Ɉ܄တύ॥ࡕϐϣғ܄٬Ҕࢧ-18ૅဏ❣ᾕਡ㧿ୀෳલՈ 19 ጰݒᐫǵጰΚഩ ߏයᕍਏ Ɉޑޣύ॥஻܄લՈٳPioglitazoneᆶPPAR-"ፓ௓ݯᕍӧᑗֿੰ 20 ቅᔮѶ ύ॥Β Ɉ܄ठϐલՈ܌ฯϯރӧᝄख़εՈᆅๆނՈλ݈ᛰלᚈጕᆶൂጕ 21 زࣴ܄ભႣٛϐߏය่݀Кၨᆶϩ݋Ǻӣྉ ችǵ੍݅Ϙ܃මη޼ǵ׵ ნ Ɉ֚ޑཥԮӦ୔୔ୱᙴଣݯᕍတ೽εՈᆅߔ༞ੰ஻ 22 ዞڷጰ 23 ቹႽᏢλՈᆅੰᡂ܈ੇଭ଑๺ᕭჹಃ΋ԛલՈ܄ύ॥ੰ஻ύ॥ࡕ΋ԃ Ɉ ϐᇡޕԔጕϐቹៜ ۇѶǵֺᅸד׵খդǵ݅դࢅǵ᝵ች੿ǵഋ 24 ࡼቺ΍ᜪᛰނё෧ϿЈ܊᠞୏ੰΓวғ࡚܄લՈ܄ύ॥ࡕᢅϣрՈว ز1ԃԝΫ౗ǺѠ᡼ࢬՉੰᏢࣴکғ౗ ᄪǵ஭ЎૈǵᐽԋᏦǵጰΏЎדඁᅩǵጰۗ⣬ǵ݅݅ ٯਢـش໺಍တՈᆅ೷ቹܭᓍ୏ેੇᆟᝠ䈜ᆅᡉܴ܄ബ໾ޑཀ᛽ምᛖ 25 ൔ֋ ܴד໳ҏනǵ׵ ᆶᖏ׉ϷགځϷڋѐ׭ޑǺၮ୏Ҝ፦ڋғ౛ᐒੰޑύ॥ࡕύኰઓ࿶ภ 26 ᝺ੱރޑ࣬ᜢ܄ ෯Ⴈ։ǵ׵ߪ፣ǵᎄࡌᑫǵᖴ݊ᇇǵԢܴᄆǵယធൈǵᖙᏢЎǵᇳ௴ຬ ਵೌࡕੰΓϐៈ౛ڗ 27 ݅ᓉᖚǵՖలൟǵ໳ᑯนǵጰྷટǵቅη๭ǵఉᑉ 28 ୷ܭుࡋᏢಞϐఒ༞܄ύ॥ᅶਁ೷ቹᒣ᛽ ǵ൹৪໋ǵഋѓጎǵЦ୯଻ǵ೾ယᐴǵጰകϘےۏጰ တύ॥܄લՈ܄࿶୏ેݯᕍᢅѦϣᓍ୏ેߔ༞ϐ࡚ 29 ᝄᝊയǵ໳हྼ 30 ύ॥ჹғࢲࠔ፦ϷрଣӼ࿼ޑቹៜ ઔǵ݅ችীذ؇

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ຎЕᄂᏽသഋЙ೚ this adaptation to the new approach was Ⲗ also analyzed. The flow of procedure andځ෯ ୯ٛᙴᏢύЈΟैᕴᙴଣઓ࿶Ѧࣽ೽ complications were recorded at outpatient follow-up. Virtual Neuro-Navigation in Reality Results: All patients experienced neurologic Surgery improvement after the operations. 79 Chi-Tun Tang patients had no recurrence and hormonal Department of Neurosurgery, Tri-Service balance at serial follow-ups, 23 patients General Hospital, National Defense Medical underwent postoperative stereotactic Center, Taipei radiosurgery on account of residual tumor. There was no catastrophic vascular Objectives: The 3D virtual image system conflict and major complications (CSF is prevailing at current modern surgeries. leaks, bacterial meningitis, stroke, etc.) in With improvement in computational power our cohort. The mean operation time and and advances in visual and haptic display maneuverability were comparable with our technologies, virtual surgical environments controlled group (p=0.01). With regard to   [    the wearing limitation, repeated training can training, planning, and rehearsal in a safe, vanish the cybersickness and it is associated simulated setting. It is readily compensated with the individual tolerance. by provide depth perception and stereotactic Conclusion: The use of the VRNAS visualization to the operator. Neural tract integrated the VR and real-time navigation is invisible under the microscope except      |[ visualized by virtual tractography by in accuracy and patients’ outcome. We computing methodology. Diffuse tensor believed there is great promising potential images (DTI) are the source to make the to mature this novel technology to guarantee tensor neural tract being able to see after the patient’s safety. combination of current navigation system – we named “Virtual Neuro-navigation”. Even though the innovative development, the ಛӫϷݙڷӱ៫ܒಛفsurgeon still needs to overcome the learning ΙӋPRISMA သϛॳ௉ܒᐭᄇᄚږࢺႫޢcascade. ௤ଆငᢓ Methods: Between 2015 and 2017, 120 ޱΰ޴ђ૖ܒ࡮ඈޟኇ៪ 2ǵླྀ۸ػ3ےpatients were selected and underwent VR ᚟໡ዝ1ǵ೚ᝬ Neuro-navigation Surgery (VRNAS). We 1, 2ଯ໢୯ैᕴᙴଣᙴᕍ೽ൺ଼ࣽ ౛ݯᕍᖏ׉റγ੤ނperformed VRNAS by aids of virtual 3D 3ऍ୯ફऊεᏢ conversion simulator (SHINKO, Tokyo, Japan) with head-mounted display (HMD, A PRISMA Systematic Review and Meta- SONY-HMZ, Tokyo, Japan) visualization. Analysis of the Effects of Transcranial The perioperative maneuverability (score Direct Current Stimulation on Upper 0-4) was compared to the other standard Extremity Functional Recovery in surgeries purely by standard navigation Patients with Chronic Stroke system with no VR assistance. The Ya-Ying Wei1, Ya-Ying Wei2, Chung-Yu Yang3 operator’s discomfort (cybersickness) in 1, 2Department of Physical Medicine and

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Rehabilitation, Kaohsiung Armed Forces via using the Cochrane risk of bias tool and General Hospital, Kaohsiung City, Taiwan; the Physiotherapy Evidence Database scale 3Doctor of Physical Therapy for Practicing (PEDro) and then synthesized the study Physical Therapists, New York University, New results. The UE functional recovery of the York City, USA real-tDCS and sham-tDCS groups was compared by calculating standardized mean Background: In the chronic phase of stroke, differences (Hedge’s g) to derive a summary an imbalance of interhemispheric excitability effect size. could hinder the motor recovery of the upper Results: Thirteen studies (295 participants extremity (UE). Transcranial direct current with chronic stroke) were included. These stimulation (tDCS) is a promising treatment studies yielded a positive effect in favor of that could promote the interhemispheric UE functional recovery, and among these balance and motor recovery by modulating studies, six studies showed that tDCS could neuronal excitability in a polarity-specific promote recovery of UE function over 40% manner. However, there is a lack of current (106 chronic stroke patients). The percentage systematic studies investigating UE of improvement is calculated thus: (post- functional recovery after receiving the tDCS tDCS - pre-tDCS) /pre-tDCS scores*100%. intervention. Therefore, the primary purpose Ten of high-quality (PEDro >7) and low- of this study is to investigate the effects of bias studies were included in the meta- tDCS on UE functional recovery in chronic analysis. A random-effects model of meta- stroke patients by a systematic review and      [ |    meta-analysis. Z = 2.66 (p = 0.008), heterogeneity: Tau² = Methods: A comprehensive database 0.06; Chi² = 11.79, df = 9 (p = 0.23); I² = search of the literature up to June 24%. Summary Hedge’s g was statistically 2019 was performed via MEDLINE, significant in favor of the real-tDCS group EMBASE, CINAHL, AMED, PubMed, (Hedge’s g = 0.44, p = 0.008), which PEDro. keywords were: (1) stroke, (2) suggested a moderate effect. cerebrovascular accident, (3) tDCS and Conclusion: In conclusion, all tDCS studies (4) upper/arm/hand. Randomized clinical support the validity of the interhemispheric trials that included tDCS intervention for balance theory. This meta-analysis study improving UE function of chronic stroke reveals a superior UE functional recovery patients were located. The primary outcome on patients of chronic stroke in the real- was clinical assessments of UE functional, tDCS group compared to patients in the based on the activity categories of sham group. As a result, the tDCS could International Classification of Functioning, be a viable intervention for chronic stroke Disability and Health (ICF), which included: patients because it is safe, cost-effective, and (1) Action Research Arm Test (ARAT), clinically convenient to be combined with (2) Wolf motor function test (WMFT), (3) other therapies. Jebsen-Taylor Hand Function Test (JHFT), (4) Motor assessment scale (MAS) and Box and Block Test of Manual Dexterity (BBT). Two review authors independently assessed the risk of bias and trial quality

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(သϛॳ antiphospholipid syndrome in 1 (5.9%ܒ੃೚ࡣԞ෈ӔีીՖڥᐠడ ௤ଆ patient, and large artery atherosclerosisחᖝޟ 1ǵ݅ࡏՎ2ǵጰΚഩ1ǵ׵஖ in 2 (11.8%) patients. Ten (58.8%) ofܸדᖙႨᏂ1ǵഋ ᆢ2ǵ෯Ⴈ։1ǵᎄࡌᑫ1 them received repeated MT, all achieving 1Ѡεᙴଣઓ࿶೽ǵ2ѠεᙴଣቹႽᙴᏢ೽ successful revascularization and none developed symptomatic hemorrhage. Early Recurrent Stroke in Patients The patients with and without ERS had Receiving Mechanical Thrombectomy comparable good functional outcome (29.4% Sung-Ju Hsueh1, Chih-Hao Chen1, Yen-Heng versus 41.0%, p = 0.31). Lin2, Li-Kai Tsai1, Chung-Wei Lee2, Sung-Chun Conclusion: ESR in stroke patients with Tang1, Jiann-Shing Jeng1 MT was not rare, and repeated MT could be 1Department of Neurology, 2Department of effective and feasible in subjects with ERS. Medical Imaging, National Taiwan University Hospital, Taipei, Taiwan

Background: Mechanical thrombectomy ᡊܘࢸЖٳRivaroxabanᇄapixabanܻ (MT) for acute ischemic stroke is a proven ᆰᠬଢ଼ఊတϞᐨ࡙Ϸݙ technique effective in selective patients. This ݒሺ1, 2ǵ೾ᒸᐇ2ǵယធൈ3ǵጰΚഩ3ǵቅ݅ study described the incidence and clinical ர4ǵ໳ᙃ޹1, 2ǵ෯Ⴈ։3ǵᎄࡌᑫ3ق characteristics of early recurrent stroke 1ѠεᙴଣᛰᏊ೽ǵ2Ѡ᡼εᏢᛰᏢ஑཰Ꮲଣᛰ (ERS) in patients receiving MT from a ǵ3Ѡεᙴଣઓ࿶೽ǵ4Ѡεᙴଣϣࣽ೽ЈسᏢ single center in Taiwan. ՈᆅύЈ Methods: We retrospectively reviewed patients who had acute ischemic stroke and received MT from January 2015 to Real World Rivaroxaban and Apixaban September 2018 at one medical center. ERS Levels in Asian Patients with Atrial  [  |     Fibrillation 1, 2 2 3 [   ©   |      Shin-Yi Lin , Ching-Hua Kuo , Shin-Joe Yeh , 3 4 1, 2 and not caused by hemorrhage within the 21 Li-Kai Tsai , Yen-Bin Liu , Chih-Fen Huang , 3 3 days after the onset of index stroke. Good Sung-Chun Tang , Jiann-Shing Jeng 1 3      [  [ Department of Pharmacy, Stroke Center and 4 Š   "Š „0ƒ ‹   Department of Neurology, Department of stroke. Internal Medicine, National Taiwan University Results: During the period, 200 patients Hospital, Taipei, Taiwan 2 (mean age 71.6 ± 12.3 years, male 49.0%) School of Pharmacy, College of Medicine, received MT. Seventeen patients (mean age National Taiwan University, Taipei, Taiwan 65.0 ± 15.5 years, male 35.3%) developed ªŠ "$\`{^`{ [   | `\{— Introduction: Although the therapeutic 13.4%). The stroke etiologies of those with index for non-vitamin K antagonist oral ERS were cardioembolism in 10 (58.8%) anticoagulants (NOAC) is wide, measuring patients, active cancer with positive NOAC level remains the most arbitrary disseminated intravascular coagulation method for evaluating the pharmacologic profiles in 4 patients (23.5%), catastrophic effect. The study aims to measure the plasma

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ޟޱᐭᄇܻသϛॳংԆږࢺႫޢlevels of rivaroxaban and apixaban among ငᢓ ـAsian atrial fibrillation (AF) patients and ኇ៪ȈΙӋಛӫϷݙं 2ǵഋ᜼Б3ےcompare the results with expected drug ᚟໡ዝ1ǵ೚ᝬ levels from clinical studies. 1, 2ଯ໢୯ैᕴᙴଣᙴᕍ೽ൺ଼ࣽ ౛ݯᕍᖏ׉റγ੤ނMethods: AF patients aged more than 20 3ऍ୯ફऊεᏢ years who took rivaroxaban or apixaban for more than 7 days were enrolled. Peak and The Effect of Transcranial Direct trough levels were collected at 1–4 hours Current Stimulation on Activities of after medication ingestion and right before Daily Living in Stroke Survivor: A the next dose, respectively. Samples were Systematic Review measured using ultra-high performance Ya-Ying Wei1, Yao-Tsung Hsu2, Qi-Fang Chen3 liquid chromatography with tandem mass 1, 2Department of Physical Medicine and spectrometry. Rehabilitation, Kaohsiung Armed Forces Results: A total of 178 patients were General Hospital, Kaohsiung, Taiwan; enrolled, 73 who took rivaroxaban (15 3Department of Physical Therapy, College of mg daily, 34 patients; 10 mg daily, 39 Health Sciences, Kaohsiung Medical University, patients) and 105 who took apixaban (5 Kaohsiung, Taiwan mg twice daily, 44 patients; 2.5 mg twice daily, 61 patients). Patients in the apixaban Background: Changes in interhemispheric group were more likely to be ordered an activation balance after the occurrence inappropriately-adjusted dose compared of a stroke have been postulated to to those in the rivaroxaban group (37.5% impede recovery of activities of daily versus 22.5%, p = 0.046). The percentage of living (ADL) among stroke patients. As those with drug levels within the expected a promising technique, transcranial direct range reported in clinical studies was current stimulation (tDCS) has gained significantly higher in the apixaban group much attention for its potential effects than in the rivaroxaban group, both for regarding restoration of motor function and trough (84.8% versus 64.4%, p = 0.002) and ADL following cases of stroke. However, peak level (76.9% versus 33.8%, p < 0.001). individual studies have yielded inconsistent After adjusting for age, sex, kidney function,   \    \•     appropriate dose and adherence, patients in review investigates the effects of tDCS on the rivaroxaban group were still less likely ADL in stroke patients. to have peak and trough levels within the Methods: Our literature search focused expected drug levels (odds ratio [OR] for on tDCS studies that have investigated trough 0.279, 95% confidence interval [CI] the effects on stroke patients’ ADL. An = 0.13–0.62, P = 0.002; for peak, OR = 0.172, initial search was carried out using the 95% CI = 0.08–0.35, P < 0.001). databases MEDLINE, EMBASE, CINAHL, Conclusion: Our real world data suggests AMED, PUBMED, PEDro, and airiti that Asian patients taking rivaroxaban are library from May 2000 until June 2019. more likely to have out-of-expected drug Four keywords were used: (1) stroke, (2) levels than those taking apixaban. cerebrovascular accident, (3) tDCS, (4) daily living. Meanwhile, search outcomes were limited to full text of articles reviewed

226 ⹛㛪⢨⠘媽㕮 that were either in the Chinese or English than the effect on patients in the control language. Studies were selected if they met group. However, the results have been the following inclusion criteria: (1) studies differentiated regarding the passage of time on stroke patients, (2) multiple sessions since stroke onset, which is known to be a of tDCS intervention, (3) assessment of crucial parameter of the focal changes of the ADL before and after the intervention, interhemispheric plasticity. The time of the (4) placebo-controlled study-design. The intervention after stroke onset likely has a primary outcome measure for clinical very significant impact on the efficacy of assessments of ADL includes: (1) Barthel tDCS intervention; however, these results index, (2) Functional independence measure, need to be confirmed by future clinical (3) Frenchay activities index, (4) Modified studies. Rankin scale, (5) Stroke specific quality of life scale. Two reviewers independently assessed the chosen body of works for bias and quality using a validated, reliable tool, ՖϛNfLᇄGFAPџႱกCADASILϞ the Cochrane Risk of Bias Tool and the ੽੾ᝒ१࡙Ѕϛॳඈี ǵ෯Ⴈ։ǵᎄࡌᑫܸדPhysiotherapy Evidence Database scale ഋ (PEDro) scale, respectively. Ѡεᙴଣઓ࿶೽ᄤတύ॥ύЈ Results: There were 37 articles found via the listed search databases. However, only six works of research literature (which included Glial Fibrillary Acidic Protein Can 180 participants in total) were included Reflect CADASIL Disease Severity based on meeting our inclusion criteria for and Predict Recurrent Stroke review. Study subjects were of the mean age Chih-Hao Chen, Sung-Chun Tang, Jiann-Shing of 55.8 (ranging from 47 to 62) years old. Jeng Additionally, studies included cases with the Stroke Center & Department of Neurology, period from stroke onset to a range of from National Taiwan University Hospital, Taipei 4.9 weeks to 33.5 months. The PEDro scores are from 8 to 11, and the bias was deemed of Objective: To investigate whether plasma low risk by the independent reviewers. These biomarkers can reflect the disease severity studies show a positive effect in regard to and predict stroke recurrence in patients ADL recovery: subjects receiving tDCS (78 with CADASIL. stroke patients) showed improvements in Methods: Sixty-three patients with ADL ranging between 1.9% and 81.3% from CADASIL (mean age 58.9±9.3 years old, baseline (with an average of 39.4%), while male 63%) and 17 controls were recruited. those “receiving” the placebo-tDCS showed Patients with CADASIL were divided into improvements in ADL ranging between 0% those without stroke (n=16), with ischemic and 55.6% (on average 20.7%). stroke (IS, n=26) only, and ever intracerebral Conclusion: In conclusion, all tDCS studies hemorrhage (ICH, n=21) based on their support the validity of the interhemispheric history upon recruitment. Plasma biomarkers balance theory. These studies show a including neurofilament light chain (NfL), positive effect on ADL recovery for stroke glial fibrillary acidic protein (GFAP), tau, patients in the real-tDCS group far greater and ubiquitin carboxy-terminal hydrolase L1

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(UCHL1) were measured by ultra-sensitive classified into the direct and indirect single molecule array. MRI markers included types, which can be attributed to trauma, Fazekas scale of white matter hyperintensity, atherosclerosis, hypertension (HTN), numbers of lacunes and cerebral microbleeds diabetes mellitus (DM), pregnancy or (CMBs). postmenopausal status. Carotid Doppler Results: The four serum biomarkers were ultrasonography (CDU) typically reveals significantly elevated in patients with    \|      CADASIL than control. Among patients resistance index (RI) in the feeding arteries, with CADASIL, those with ICH had highest which can assist in the diagnosis. We herein serum GFAP compared with no stroke or IS report a case of indirect CCF presenting groups. Higher NfL and GFAP correlated with high RI in the feeding arteries, which with lower MMSE (s=-0.44 and -0.52, was mainly attributed to the generalized respectively), higher Fazekas scale (s=0.26 atherosclerotic change, and was regarded as and 0.50, respectively), and CMBs count diagnostic pitfall of CCF. (s=0.38 and 0.42, respectively; all P<0.05). Within a median follow-up of 3.1±2.1 years, 9 patients (14.3%) had at least one recurrent ੿ঐတᔣفstroke. A cox regression analysis showed သཆϛॳ੾௉֕౪ϱ୏ᒧ ൢ֙ٽthat higher NfL (HR=1.89, 95% CI=1.15– խᓛොડငਲ਼੾ᡐȈΙ੾ 3.82) or GFAP (HR=1.90, 95% CI=1.14– ᗛइ୻ at baseline were associated with stroke ߞကᙴᕍ଄იݤΓଯ໢୷࿎௲ᙴଣ (3.16 recurrence. Conclusions: Serum NfL and GFAP can Medial Lemniscus Syndrome be promising biomarkers in reflecting Masquerading Cervical Radiculopathy the disease burden and monitoring stroke in a Brain Stem Stroke Patient: A Case occurrence in patients with CADASIL. Report Chi-Pei Chung Department of Neurology, Lutheran Medical Foundation Kaohsiung Christian Hospital, ᢓՖᆓ຺ॱݰᄇܻᓛଢ଼૕.੕ᆭᝮ⥝ᆓ Kaohsiung, Taiwan ൢ֙ٽຨᘞഞ٫ȈΙ੾ޟ ഋ࢙Ӽ1ǵ݅╈൛2 Background and Purpose: Two main 1ѠчѱҥᖄӝᙴଣϘངଣ୔ somatosensory tracts exist: The medial ,ᙴଣ lemniscus responsible for light touchۺ2Ѡчଭିइ proprioception and vibration and the High Resistance Index in the Feeding spinothalamic tract responsible for sensing Arteries of Indirect Carotid-Cavernous pain and body temperature, disturbance of Fistula: A Diagnostic Pitfall deep and discriminative sensory perception. Bo-An Cheni1, Wei-Ting Lin2 Infarction of medial lemniscus could present 1Taipei City Hospital, Renai Branch, Taipei; symptom mimic cervical radiculopathy. 2Mackay Memorial Hospital, Taipei Case Report: A 52-year-old man presented with sudden onset of sensory disturbance Carotid-cavernous fistulae (CCFs) are and numbness over right hand, forearm, arm

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(ventral and dorsal parts). Initially, cervical University of California, Los Angeles, USA multiple radiculopathy was suspected, then sensory disturbance migrating to right Non-Inferiority Margins in Trials of flank and knee. His past history included Thrombectomy Devices for Acute hypertension without regular control, Ischemic Stroke: Is the Bar Being Set hyperlipidemia without control, and heavy Too Low? smoker. On neurological assessment and Chun-Jen Lin1, Jeffrey L. Saver2 examination, there was only paresthesia 1 Division of Cerebrovascular Diseases, and reduced perception of right upper Neurological Institute, Taipei Veterans General limb to light touch as well as vibratory Hospital, Taiwan and proprioceptive stimuli over left C5678 2 Comprehensive Stroke Center and Department dermatome, other neurological examination of Neurology, David Geffen School of Medicine, were within normal limits including cranial University of California, Los Angeles, USA nerve ,motor systems and cerebellar systems. Brain Magnetic resonance image showed Background and Purpose: Novel hypointensity lacune signal in tegmentum endovascular mechanical therapy (EVT) part of left mid-pons level in T2. Lab data devices for acute ischemic stroke (AIS) are also revealed hyperlipidemia as TG 661, often cleared by regulatory agencies on the Cholesterol 301, LDL 144. basis of non-inferiority trials. The relation Conclusion: MRI confirmed an acute between the non-inferiority margins used in infarction of a paramedian branch of the trials and the minimal clinically important basilar artery in the left medial lemniscus differences (MCIDs) determined by experts in a patient presenting as mimic cervical has not been systematically investigated. radiculopathy. Sensory projections from Methods: Systematic searches were the face, arm, and leg are somatotopically performed to identify: 1) all non-inferiority arranged medially to laterally within the design or non-inferiority-presented stroke- medial lemniscus in the posterior column EVT trials for AIS, 2) all studies determining pathway. It is possible that the infarction of the MCIDs for the same outcomes, and 3) medial meniscus mimic polyneuropathy or all non-inferiority coronary revascularization cervical or lumbar radiculopathy. Although trials. Stroke-EVT trial results were re- strokes classically present with numbness, analyzed using the broad non-inferiority medial lemniscal infarcts can presents margins originally employed and narrower as acute paresthesia as radicular sensory non-inferiority margins derived from formal symptoms without dermatome distributions. MCID studies. Results: We identified 7 non-inferiority designed or non-inferiority interpreted stroke-EVT controlled trials, enrolling patients, variously comparing coil 1,766 ܒ੃ၐᡛϞߨӛڥသϛॳܒીՖܒࡨ ᖝࣨ঄Ϟ௤ଆ retrievers, 1st and 2nd generation stent ੍݅Ϙ 1ǵJeffrey L. Saver2 retrievers, and aspiration devices. In 6 trials, 1ᆵчᄪ҇ᕴᙴଣઓ࿶ϣࣽ the primary outcome was achievement of 2Comprehensive Stroke Center and Department reperfusion, using non-inferiority margins of Neurology, David Geffen School of Medicine, of 15% (3 trials), 10% (2 trials), and 8%

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(1 trial). In contrast, a stroke expert survey 3Emergent Medicine, Chi-Mei Medical Center,  [!™     ‹\}— Tainan, Taiwan 5%, and cardiac trials used non-inferiority margins of 3.5-4.4%. In one stroke-EVT Introduction ƒ‚}ƒ—}$  [  trial, the primary outcome was functional care model (hospitalist care model-HCM) independence, employing a non-inferiority with 8 medical sub-specialists at emergency margin of 15%. However, two stroke department(ED) to care all pre-hospitalized expert survey studies identified MCIDs for patientswith 3 shifting-duty works within functional independence as having lower 24 hours. The mortality rate, waiting time, values, 5% and 1-1.5%. For both reperfusion 6- and 24-hour deterioration after admission and functional independence outcomes, all were declined, and patient satisfaction was 7 trials demonstrated non-inferiority with higher over 90% by the collaboration with the broadest non-inferiority margin, but only ED physicians. 4 and 3 trials demonstrated non-inferiority Purpose: To understand weather this HCM with actual expert-derived margins for  |[   [   reperfusion and functional independence, in stroke patients. respectively. Methods: One qualified hospitalist, Conclusion: Non-inferiority margins certified by Taiwan Neurology Society, employed in EVT device trials have participated in the care of stroke patients regularly exceeded the MCIDs determined referred by emergency physicians at ED for by stroke experts, as well as margins used admission since 2012, with a duty consultant for cardiac devices. New approaches, such as neurologist. Both hospitalist and neurologist the use of reasonably adequate performance shared decisions making for copy strategy margins, rather than non-inferiority margins, and specific tests including lipid profile, are needed to optimize stroke-EVT trial carotid Doppler, and neuroimaging design integrity and trial performance study (exp., magnetic resonance image- feasibility. MRI),which were supposed to be performed after hospitalization in most hospitals in Taiwan. We compared several parameters before and after setting this HCM to realize ᐌӫऋᖒӫྱ៖ᄇܻϛॳ੾ the impacts to stroke patients the efficacyڷડငऋ Ρޟኇ៪ [  \ ଯക1, 2ǵ݅ችী2ǵ׵ྷน1ǵ೚ࡌమ3ǵླྀ Results: Three time period was divided݅ ੍ሎ2 before and after setting HCM (2010- ऍᙴଣઓ࿶ϣࣽǵ 8~2012-7; 2012-8~2015-7; 2015-8~2018-ڻऍᙴଣӄΓᙴᕍࣽǵ2ڻ1 = ऍᙴଣ࡚ບ೽ 7) by excluding patients died at ED (nڻ3 23), and direct admission without stopover Impacts to Stroke Patients Under (n = 1149). Totally, 6299 were analyzed Hospitalist and Neurologist Combined for demographics. Sex (M : F = 1.5 : 1), Care Model NIHSS at admission was 3 (1-7 of inter- Kao-Chang Lin1, 2, Huey-Juan Lin2, Jei-Chi Li1, quartile range-IQR), length of stay at Chien-Chin Hsu3, Chun-Ming Yang2 wards 2 was 5 (3-9 of IQR), and modified 1Department of Holistic Care, 2Neurology, ranking scale at discharge was 2 (1-4 of

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IQR) without statistically significant. The 2 Department of Neurology, Chiayi Chang Gung over-waiting time (24~48 hours) in pre- Memorial Hospital, Chiayi, Taiwan hospitalized period at ED declined, and the complete necessary studies increased, both Background: Several risk score models was statistically significant (p < 0.05). The were developed to predict symptomatic increase rate of specific tests at ED saved intracranial hemorrhage (SICH) after much time of delaying decision to perform intravenous thrombolysis, while the further procedures in next steps. risk models for predicting SICH after Conclusion: Our study, setting a new HCM endovascular thrombectomy (EVT) were at ED, saved pre-hospitalized boarding time limited. The study aimed to use previously especially on long waiting period over 24 established risk scores for intravenous hours for stroke patients. The efficiency of thrombolysis to predict SICH after EVT. Doppler study, lipid profile, and MRI was Methods: Patients with anterior circulation earlier performed at ED by the collaboration large vessel occlusion who received EVT between hospitalist and neurologist to in two medical centers were recruited. make earlier decision for precise treatment Two definition of SICH, the European compared to not setting this model. Although Collaborative Acute Stroke Study II the mortality, disease severity, and length (ECASS II) and the Safe Implementation of stay at wards of stroke patients did not of Thrombolysis in Stroke-Monitoring reduce in our analysis may due to variable Study (SITS-MOST), were used. etiologies, the impacts to stroke patients for Previously developed risk scores including fast diagnosis and better decision making in the Hemorrhage After Thrombolysis treatment are mandatory importance. (HAT) score, the Safe Implementation of Thrombolysis in stroke (SITS) SICH risk score, and the SEDAN score, were calculated. Logistic regression and area ଢ଼૕ϱՖ੃ಋଶ೚ࡣีҡ੿ޑܒသю under a receiver operating characteristic ՖϞॳᓎຟե curve (AUC-ROC) were used to evaluate the 2ǵ෯Ⴈ։ effectiveness and performance of each riskۏ1ǵ݅։፣2ǵ׵ܸדഡ໺অ1ǵഋ 1ǵᎄࡌᑫ1 model. 1Ѡεᙴଣတύ॥ύЈ Results: A total of 243 patients (mean 2჏ကߏ۪ᙴଣઓ࿶ϣࣽ age 71.8 ± 12.6 years; men: 47.4%) were included in this study. The observed rate of Risk-scoring Systems in Predicting !’ª!› [   }}\`{"ƒ$ Symptomatic Intracranial cases), which was higher than the predicted Hemorrhage after Endovascular rates by the HAT score (10.5%) and SITS- Thrombectomy SICH risk score (6.5%), while lower than Chuan-Hsiu Fu1, Chih-Hao Chen1, Chun-Hsien predicted rate by the SEDAN score (11.6%). Lin2, Meng Lee2, Sung-Chun Tang1, Jiann-Shing The observed rates of SICH by SITS-MOST Jeng1 definition was 4.9%, which was higher 1 Stroke Center and Department of Neurology, than the predicted rates by the SITS-SICH National Taiwan University Hospital, Taipei, risk score (2.3%). The SEDAN score was a Taiwan significant predictor for SICH by ECASSII

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 • —¢ •[  "¢Š}\`  3 Graduate Institute of Clinical Medical Science, 1.96 per score increase, respectively; both P China Medical University, Taichung, Taiwan < 0.05), while the HAT score only predicted 4 National Institute of Neurological Disorders SICH by ECASSII definition (OR = 1.45, and Stroke, National Institutes of Health, USA P = 0.04) and the SITS-SICH risk score by SITS-MOST definition (OR = 1.37, P Introduction: Registry-based stroke research = 0.05). The AUC-ROC was highest when has provided real-world evidence on the using the SEDAN score to predict SICH by performance and quality of clinical care • —¢ •[  "‚\Œ}^`{!‚\`— among different regions in the world. 0.86). In multivariate logistic regression We aimed to compare the outcome of analysis, atrial fibrillation, procedure time intravenous thrombolysis treated patients and presence of CT hypodensity were from two stroke registries in Taiwan and the independent risk factors for SICH after United States. EVT by ECASSII definition, while age, Methods: There were 122,191 stroke cases serum glucose level and presence of CT from Taiwan Stroke Registry (TSR) and hypodensity predicted SICH by SITS-MOST 10,981 from National Institute of Health- [  \ funded SPOTRIAS network. Among them, Conclusion: The SICH after EVT in our we analyzed 3302 patients in TSR and 3002 study occurred at a rate of 11.5% and 4.9% in SPOTRIAS treated with intravenous by ECASSII and SITS-MOST definition. thrombolysis with available clinical The SEDAN score could be a practical tool information. to predict SICH after EVT. Results: The mean age of patients (68.2±12.5 vs 67.8±12.5 years) and initial NIHSS score (13.0±7.3 vs 13.0±7.5) were comparable between the two registries, while the Ѯछϛॳิᓃϛࢊ҈Ֆ੃ྙ၌Ꮨ੾௉ prevalence vascular risk factors were higher ϞШၶ in TSR. The door-to-needle time was 1ǵഋҏ๭2ǵᎄࡌᑫ1ǵ೚ख़က3ǵणඦ significantly faster in the TSR (median 55ܸדഋ ࡹ4 min, IQR 42 to 77) than SPOTRIAS (65 min, 1Ѡεᙴଣઓ࿶೽ IQR 45 to 90; P < 0.001). The proportion of patients with favorable outcome (modified سၗૻᆶᙴᏢπำᏢނ2٥ࢪεᏢғ Rankin scale 0 and 1) at discharge were ܌ز3ύ୯ᙴᛰεᏢᖏ׉ᙴᏢࣴ 4ऍ୯୯ৎፁғଣ higher in TSR than SPOTRIAS (29.7% vs 22.5%, P < 0.001). Combining age, NIHSS, Comparison of Intravenous Thrombolysis door-to-needle time can have good accuracy Treated Patients Between Stroke Registry in predicting favorable outcome in TSR (area in Taiwan and the United States under the curve [AUC] 0.72), SPOTRIAS Chih-Hao Chen1, Yu-Ching Chen2, Jiann-Shing (AUC 0.79) and overall patients (AUC 0.74). Jeng1, Chung Y. Hsu3, Yang C. Fann4 Conclusion: We found certain degree of 1 Department of Neurology, National Taiwan differences in clinical features and practice University Hospital, Taipei, Taiwan of intravenous thrombolysis between Taiwan 2 Department of Bioinformatics and Medical and the United States, while the predictors for Engineering, Asia University, Taichung, Taiwan clinical outcome were universally similar.

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ඹӵܒ୑ᡩ୑ᓞฮϞีհ෈ᇄϚีհ during the events. As a result, according to ෈ޟғυᘞቹഅኇШၶ       !  [   ࢙݅՘1ǵ൹৪໋2ǵЀ३ҏ1 of Headache Disorder III (ICHD- 1Ѡчᄪ҇ᕴᙴଣઓ࿶ϣࣽ III), sporadic hemiplegic migraine was 2ѠчᙴᏢεᏢ diagnosed. We further did brain subtraction of ictal-interictal FDG-PET co-registered to Ictal-Interical Comparison of FDG- MRI for image analysis to demonstrate its PET Findings in Sporadic Hemiplegic underlying pathophysiology. Activation level Migraine threshold was set to 1.5 standard deviations. Po-Tso Lin1, Syu-Jyun Peng2, Hsiang-Yu Yu1 In comparison with interictal state, the FDG- 1 Department of Neurology, Neurological PET image showed decreased brain glucose Institute, Taipei Veterans General Hospital, metabolism in the bilateral dorsal lateral Taipei, Taiwan frontal cortices and the bilateral occipital 2 Professional Master Program in Artificial cortices, whereas increased metabolism was Intelligence in Medicine, Taipei Medical observed in the left precentral motor cortex University, Taipei, Taiwan and right premotor cortex. Conclusion: These findings reveal an Background: Sporadic hemiplegic migraine increase in metabolism in the contralateral (SHM) is regarded as prolonged motor aura motor and ipsilateral premotor cortex during when migraine attack and its underlying general cortical dysfunction in the frontal pathophysiology remained unclear. It is and occipital cortex in SHM. among one kind of stroke mimics. Case report «   }$—\ š   positron emission tomography (FDG-PET) ݲҀ࿅Ъ੿ȃଽૌₕሖځӫܒظfinding in a 15-year-old female of sporadic ԑሆ hemiplegic migraine. She presented with Ֆ੿ЅဨሖીмีҡІ᙭ϛॳȈΙਰ ൢ֙ٽ recurrent right distal arm weakness twice ՙڂa week that each time lasted for around 3 ݅դࢅǵ݅ hours to 3 days. The hemiplegic migraine ԋεᙴଣઓ࿶೽ attack started with right limb weakness followed by right upper limb pain and Recurrent Ischemic Stroke in A Young shoulder pain. Throbbing headache at Male with Concurrent Fabry Disease, right temporal region soon evolved. It was Hyperhomocysteinemia and Folic Acid moderate to severe in intensity, aggravated by physical activity and was accompanied Po-Yu Lin, Tien-Yu Lin by nausea, vomiting, photophobia and Department of Neurology, National Cheng Kung phonophobia. The headache disappeared University Hospital, Tainan, Taiwan before weakness recovered. It was regarded          [ \ Background: Fabry disease is a Brain magnetic resonance imaging (MRI) risk factor of ischemic stroke, as are was normal and without evidence of acute hyperhomocysteinemia and folic acid infarction. Video electroencephalogram deficiency. Here we reported a case showed no evidence of epilepsy in nature of recurrent ischemic stroke who had

233 ⹛㛪⢨⠘媽㕮 concurrent Fabry disease, elevated serum thrombolysis, because of the high potentials      [  \ of massive bleeding. We present a case of Case Report: A 44-year-old male patient dissecting aneurysm presenting with acute had history of ischemic stroke in brainstem ischemic stroke and receiving intravenous years ago. He presented with acute onset thrombolysis. occipital headache, blurred vision and Case Report: An 86-year-old hypertensive transient vertigo. Acute ischemic stroke man presented to our emergency room due in bilateral occipital lobes was diagnosed to acute left hemiparesis for 2 hours. The through brain MRI. Stroke risk factor survey initial National Institutes of Health Stroke revealed hypertension, tobacco use, Fabry Scale (NIHSS) score was 5, and non- disease (GLA gene mutation, c.658C>T), contrast computed tomography (CT) of brain     "}^\}) £„ did not show intracerebral hemorrhage. and low serum folic acid (3.2 ng/mL). The However, routine chest x-ray showed a underlying pathophysiology of cerebral suspicious aortic aneurysm. After a thorough vascular involvement in Fabry disease is not discussion with the patient and his family yet fully understood. In previous reports, about the benefit and risk of thrombolysis, serum homocysteine was higher in patients intravenous alteplase was still administered. with Fabry disease comparing to normal After 24 hours, his NIHSS score improved control. Serum folic acid was also found to to 2. Magnetic resonance images of brain be decreased in patients with Fabry disease. showed acute infarct at right pre-central Conclusion: We reported this case to gyrus without hemorrhagic transformation. highlight the possible correlation between Contrast CT of chest showed a thrombosed Fabry disease, hyperhomocysteinemia and dissecting aneurysm at the aortic arch folic acid deficiency, and emphasis the without evidences of bleeding. He was    |     [    discharged to post-acute ward about 1 week factor in patient with ischemic stroke. after stroke onset. At 1 month, the functional status was almost back to his baseline. Conclusion: Despite the high risk of bleeding, intravenous thrombolysis was effective ીՖ and without bleeding complications in thisܒҢܻΙ՝ࡨٺᓗ૕Ֆ੃ྙ၌Ꮨ кଢ଼ଢ଼૕ዴϞ੾Ρ elderly stroke patients with dissecting aorticܒথᚔځϛॳӫܒ ᖴᙼ໚ aneurysm. Further study may be warranted Ѡࠄཥኴᙴଣઓ࿶ࣽ to determine the safety and efficacy of intravenous thrombolysis in such patients. Intravenous Thrombolysis in a Patient with Acute Ischemic Stroke and Dissecting Aortic Aneurysm Cheng-Yang Hsieh ࡨܒીՖϛॳଢ଼૕ϱՖ੃ಋଶ೚ࡣϞ Department of Neurology, Tainan Sin Lau ᡗኇᏘသ੾ᡐ 1 1 2 1 ǵ׵஖ᆢ ǵጰΚഩ ǵ෯Ⴈ ܸדHospital, Tainan, Taiwan ԙ҉ၩ ǵഋ ։1ǵᎄࡌᑫ1 Background and purpose: Aneurysm is a 1Ѡεᙴଣઓ࿶೽ᄤတύ॥ύЈǵ2ቹႽᙴᏢ೽ contraindicated condition for intravenous

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Contrast-Induced Encephalopathy of old right middle cerebral artery (MCA) after Endovascular Thrombectomy for infarct attributed to infective endocarditis, Acute Ischemic Stroke who developed sudden onset of aphasia. Yung-Tsai Chu1, Chih-Hao Chen1, Chung-Wei Perfusion CT showed left MCA posterior Lee2, Li-Kai Tsai1, Sung-Chun Tang1, Jiann- M2 territory infarct, and he underwent ET Shing Jeng1 with successful recanalization (TICI 3). 1 Department of Neurology and Stroke Center, However, he was semi-comatose after the 2 Department of Radiology, National Taiwan procedure and later developed generalized University Hospital, Taipei, Taiwan tonic-clonic seizure. Emergent CT showed diffuse swelling of the whole left hemisphere Background: Contrast-induced encephalopathy with CL. Magnetic resonance imaging (CIE) is a rare complication of endovascular (MRI) on the next day showed infarct core thrombectomy (EVT). This study aimed to only in posterior M2 territory with gyral T2 investigate the incidence and risk factors of hyperintensity in the left hemisphere. He CIE in patients undergoing EVT for acute gradually regained his consciousness and CT ischemic strokes (AIS). after one week revealed total resolution of Methods: Patients who experienced AIS cerebral edema. and received endovascular thrombectomy Conclusion: This study described the during the period of September 2014 to incidence and risk factors of CIE after EVT. August 2019 at National Taiwan University CIE should be suspected in patients with Hospital were included. Contrast leakage clinical worsening and evident CL after "!£„ [      EVT. medium after EVT on follow-up computed tomography (CT) within 24 hours. CIE was defined clinico-radiologically. Clinically, ϛॳϞᏗՖনஅܒюՖځthe patients experienced neurological သᓗ૕੃༬ ൢ֙ٽdeterioration which cannot be explained by ӰཱིएᡐF2 p.F382Lਰ ች1, 2܃the infarct or hemorrhagic transformation. ݅ຐဖ1ǵ஭Κ㗟2ǵᗛ߀๩1, 3ǵ׵ Radiologically, the image showed CL plus 1Ѡчᄪ҇ᕴᙴଣઓ࿶ϣࣽ ܌زedematous changes possibly extending 2୯ҥ໚ܴεᏢတࣽᏢࣴ سbeyond the infarct core. The incidence and 3୯ҥ໚ܴεᏢᙴᏢ possible risk factors of CL and CIE were analyzed. Hemorrhagic Stroke and Cerebral Results: Of 270 patients who received EVT, Venous Thrombosis with a Novel four (1.5%) patients developed CIE and Prothrombin Gene Variant F2 p.F382L additional seven patients (2.6%) had CL on Yung-Shuan Lin1, Li-Hsin Chang2, Chih-Ping follow-up images after ET. The manifestation Chung1, 3, I-Hui Lee1, 2 of CIE included seizures, altered mental 1 Department of Neurology, Neurological status and prolonged neurological recovery. Institute, Taipei Veterans General Hospital, The risk factors of CIE were prior history Taipei, Taiwan of stroke, renal dysfunction, heart diseases 2 Institute of Brain Science, Brain Research and posterior circulation strokes. One index Center, National Yang-Ming University, Taipei, patient was a 61-year-old man with history Taiwan

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3 Faculty of Medicine, National Yang-Ming demonstrates a familial young hemorrhagic University School of Medicine, Taipei, Taiwan stroke with CVT and thrombophilia. Early  [        Acute intracranial hemorrhage with cerebral timely anticoagulation therapy are important venous thrombosis (CVT) is sometimes for preventing neurological deterioration and under-diagnosed and life-threatening, which good functional recovery. presents with a wide spectrum of clinical symptoms. We present a young 21-year- old woman having hereditary hemorrhagic ڥသϛॳଢ଼૕Ֆܒstroke and CVT with a novel prothrombin င޵ଢ଼૕໌՗ીՖ Ӗൢ֙فٽF2 gene variant. She presented with febrile ಋଶ೚Ȉ੾ episode followed by a week of posterior ԙੇྷ1ǵ݅ࡏՎ2ǵ෯Ⴈ։1ǵ׵஖ᆢ2 headache, blurred vision and increased 1Ѡεᙴଣઓ࿶೽ᄤတύ॥ύЈǵ2ቹႽᙴᏢ೽ somnolence. She rapidly developed clustered generalized tonic-clonic seizures A Case Series of Transbrachial and became comatose, and was intubated Artery Approach for Endovascular for airway protection. The neurological Thrombectomy in Acute Ischemic Stroke examination showed skew eye deviation, Hai-Jui Chu1, Yen-Heng Lin2, Sung-Chun Tang1, \    © \š  Chung-Wei Lee2 and presence of bilateral Babinski sign. Her 1Department of Neurology and Stroke Center, brain magnetic resonance imaging revealed 2Department of Medical Imaging, National acute intracranial hemorrhage in bilateral Taiwan University Hospital, Taipei, Taiwan frontal and parietal lobe with superior sagittal sinus thrombosis and marked Background and Purpose: Endovascular vasogenic edema, which led to midline thrombectomy (EVT) has become the shifting and impending uncal herniation. standard of care for selected patients She was given subcutaneous low molecular with acute ischemic stroke. Although the weight heparin with bridging to Warfarin. transfemoral arterial approach (TFA) has The patient recovered well and walked been the conventional approach for EVT, without aids on day 30 (modified Rankin transbrachial artery approach (TBA) could Scale of 3) and functionally normalized at 6 be alternative, but rarely described before. months. There was a strong family history In this study, we reported a case series of of venous thromboembolism. Her mother stroke patients receiving EVT via TBA and had four episodes of deep vein thrombosis compared their clinical parameters with and her maternal uncle died of extensive those via TFA. pulmonary embolism in his twenties. The Methods: The prospective registry for laboratory tests disclosed abnormally patients who received EVT for acute low circulating coagulation factor II ischemic stroke at National Taiwan (prothrombin). Whole exome sequencing University Hospital between September revealed a novel F2 p.F382L (c.C1146A) 2014 and September 2019 were reviewed. variant, which was highly evolutionary The demographic features, reasons for TBA, conserved and possibly pathogenic techniques used and outcomes including by in silico prediction tools. This case modified Rankin Scale at 90 days were

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သܒҢࢵ.18૓ဝ⤉℻ਯ୎กીՖٺ .collected Results: Seventeen patients (mean age: 79.4 ϛॳࡣϞϱҡܒડငཆಠफ years; men: 47.1%) out of 284 (5.9%) ጰݒᐫ1ǵጰΚഩ2 9.3 ± underwent suction-based thrombectomy 1Ѡεᙴଣчៈϩଣઓ࿶ࣽ via TBA. The median (IQR) NIHSS were 2Ѡεᙴଣઓ࿶೽ᄤတύ॥ύЈ 18(14-22). Thirteen (76.5%) patients were through right TBA including 8 (7.1%) Detecting Endogenous Neurogenesis right anterior circulation, 3 (17.6%) left after Ischemic Stroke: F-18- anterior circulation and 2 (11.8%) posterior !"# circulation. Four (23.5%) patients received Hsin-Hsi Tsai1, Li-Kai Tsai2 left TBA, 2 (11.8%) for posterior circulation, 1 Neurology Department, National Taiwan and 2 (11.8%) for left anterior circulation University Hospital Beihu Branch, Taipei, after aortic arch surgery with left subclavian- Taiwan carotid bypasses. Twelve (70.6%) patients 2 Neurology Department, National Taiwan received primary TBA while the others University Hospital, Taipei, Taiwan received TBA following failed TFA. The major reasons for TBA were unfavorable Background and Purpose: Adult neural aortic arch anatomy for TFA and vessel stem cells (NSCs) can be activated after tortuosity. Successful recanalization (mTICI stroke, but currently noninvasive imaging 2b-3) were achieved in 13(76.5%) with technique to visualize cerebral neurogenesis a median puncture to recanalization time is lacking. F-18-fluorothymidine (FLT) has as 15(11-21) min in primary TBA and been used as a PET tracer to image cell 50(39-166) min in switching from TFA. proliferation and could detect endogenous One had pseudoaneurysm formation by NSCs in vivo. In this study, we assessed the manual compression and the other one had change in cerebral FLT uptake in a rat model brachial artery occlusion by closure device of ischemic stroke. at puncture sites. Comparing to those with Methods: Cerebral FLT PET was performed TFA, patients with TBA were older, more in rats subjected to transient middle prior stroke and less intravenous rt-PA cerebral artery occlusion (MCAO). PET use. The rates of successful recanalization, data were semiquantitatively analyzed and symptomatic hemorrhage and mortality expressed as average mean standardized were similar but the percentage of functional uptake value ratios (SUVRs) of regions independence was significantly lower in of interest using cerebellar cortex as the patients via TBA comparing to those via reference region. Neurological function TFA. was assessed via modified Neurological Conclusion: TBA could be an alternative Severity Score (mNSS) 1 day after MCAO, route for EVT with good recanalization and and infarct volume was analyzed by acceptable complication rates, especially for 2,3,5-Triphenyltetrazolium chloride staining those with failure of EVT via TFA. method 7 days after MCAO. Results: Seven days after MCAO, rats exhibited a higher number of Ki67 immunoreactive cells at the subventricular zone, striatum, frontal and temporal

237 ⹛㛪⢨⠘媽㕮 cortices in the infarcted brain, indicating cardiovascular benefits in type 2 diabetic promotion of neurogenesis. The FLT PET (T2DM) patients after ischemic stroke showed higher SUVR in the infarcted brain (IS). However, whether there are additional compared to the unaffected side (Striatum: [   |††›Š—"   1.03 ± 0.36 vs 0.74 ± 0.16, p = 0.001; treatments in Asian patients with T2DM Frontal: 1.14 ± 0.27 vs 0.96 ± 0.13, p = after IS remains unknown. 0.004; Temporal: 1.16 ± 0.26 vs 1.00 ± 0.15, Methods: Between 2001 and 2013, patients p = 0.01). The cerebral FLT binding activity admitted due to IS were identified from gradually declined from post MCAO day the National Health Insurance Research 7 to day 28 in the infarcted brain. The FLT Database of Taiwan. Patients with T2DM binding ratio (global SUVR in the infarcted and hypertension using angiotensin receptor brain divided by that in the contralateral blockers were further included. Eligible side) was positively correlated to the patients were divided into 2 groups: (1) severity of stroke, including mNSS (r = 0.70, pioglitazone and (2) non-pioglitazone oral p < 0.001) and infarct volume (r = 0.90, p < antidiabetic agents groups. Propensity 0.001). score matching (1 : 2) was used to balance Conclusion: In vivo FLT PET can detect the distribution of baseline characteristics, NSCs in a rat model of ischemic stroke. The stroke severity and medications. The primary promising results of FLT PET suggest that it outcome was recurrent IS. Subgroup analysis can be potentially applied in clinical studies for recurrent IS in pioglitazone and/or as noninvasive longitudinal monitoring and telmisartan users, the trend of IS risks across ­  [  – !  |     ††›Š—"      in the human brain. dose-dependent outcomes across different pioglitazone possession ratios were further studied. Statistical significance was set at p < 0.05 and p < 0.1 for clinical outcomes ,Pioglitazoneᇄ"፡௡ݽᕛӵᑥ and interaction of subgroup analyses .ߝ෈ᕛਝ respectivelyޟޱϛॳ௉ܒીՖځ׍੾ ቅᔮѶ Results: Patients of the pioglitazone αߏ۪ᙴଣઓ࿶ϣࣽᄤတύ॥ύЈ group had a lower risk of recurrent IS݅ (subdistribution hazard ratio, 0.91; 95% %"& [   | ‚\$—‚\^^„\†   © Treatment in Type 2 Diabetic Patients was also associated with reduced recurrent after Ischemic Stroke: a national IS in patients who also used telmisartan (p cohort study for interaction = 0.071). A graded correlation Chi-Hung Liu was found a borderline significant trend Stroke Center and Department of Neurology,   ††›Š—"  Linkou Chang Gung Memorial Hospital, and following IS (p = 0.076). The dose- Taoyuan, Taiwan dependent outcome also showed a borderline significant trend that higher pioglitazone Background and purpose: Peroxisome possession ratio was associated with a lower     —  |    —" risk of recurrent IS (p = 0.068). "††›Š—"„      | Conclusions: This study suggests that

238 ⹛㛪⢨⠘媽㕮

pioglitazone use in diabetic IS patients is stroke recurrence without increasing major associated with fewer recurrent IS events in       1`‚{  Asian population. Patients with concurrent intra- or extracranial large arteries. However, telmisartan use or a higher pioglitazone it has been challenging to determine a possession ratio may have a trend of [—    — ™›†•  increased pleiotropic effects due to the stroke patients with severe cervico-cerebral   ††›Š—"   \ large artery stenosis. The purpose of this study was to compare the clinical outcomes of DAPT or mono antiplatelet therapy (MT) in our ischemic stroke patients with cervico- cerebral large artery atherosclerosis. ӵᝒ१σՖސՖωݖ᛾תᚖጣᇄ൐ጣ Methods: We conducted a preliminary ᆓ๔ޑ฽ϽܚमϞીՖܒϛॳΠ઻Ⴑ retrospective study for ischemic stroke ंܒШၶᇄϷݙȈӱྗݎ٩Ϟߝ෈๖ patients with cervico-cerebral large artery ـ 1`‚{    Š   1 1, 2 1, 3 ች ǵ੍݅Ϙ at Taipei Veterans General Hospital܃මη޼ ǵ׵ 1 Ѡчᄪᕴઓ࿶ϣࣽ between January 1, 2017 and April 30, 2 We analyzed vascular risk factors .2017 ܌ز୯ҥ໚ܴεᏢတࣽᏢࣴ 3 ,including hypertension, diabetes mellitus) س୯ҥ໚ܴεᏢᙴᏢ hyperlipidemia, coronary artery disease Long-Term Outcomes of Dual Versus and smoking), anti-thrombotic regimens Single Antiplatelet Therapy For and clinical outcomes. Patients using any Secondary Stroke Prevention in    ƒ      1‹ Patients with Severe Large Artery months were defined as the DAPT group. Atherosclerosis: A Retrospective Study Those treated with single antiplatelet or 1 1, 2 1, 3 Tzu-Yun Tseng , I-Hui Lee , Chun-Jen Lin ™›†•   ‹ [  1 Department of Neurology, Neurological the MT group. The outcome measurements Institute, Taipei Veterans General Hospital,       " [ Taipei, Taiwan Rankin Scale, mRS 0-2) at 3 months and 2 Institute of Brain Science, Brain Research 1 year after stroke, recurrent ischemic Center, National Yang-Ming University, Taipei, stroke, hemorrhagic stroke and major Taiwan gastrointestinal (GI) bleeding. 3 School of Medicine, National Yang-Ming Results: During the study period, 106 out University, Taipei, Taiwan of 381 ischemic stroke patients (27.8%) fulfilled our criteria. 57 (53.8%) were in Background and Purpose: Dual antiplatelet the MT group and 32 (30.2%) were in the therapy (DAPT), such as aspirin plus DAPT group, 17 (16%) were no treatment clopidogrel, for months is generally a or using only anti-coagulants. The basic cornerstone of the medical therapy for characteristics including vascular risk      1`‚{  factors did not differ between groups. artery atherosclerosis. A recent study There was no significant difference in the showed that long-term (>12 months) use of proportion of functional independence at aspirin plus cilostazol significantly reduced 3-month and 1-year follow-up (p = 0.084

239 ⹛㛪⢨⠘媽㕮 and p = 0.471, respectively). The 1-year patients with LVO are transferred to primary risk of recurrent ischemic stroke was 6.5% stroke center. We reported the results in in the MT group and 7.1% in the DAPT transferred/non-transferred patients with group (p = 0.464), and the risk of major GI LVO in Hsinchu regional hospital. bleeding was 10.9% in the MT group and Method: The AIS patients within 3~4.5 3.6% in the DAPT group (p = 0.399). There hours were given intravenous thrombolysis was no hemorrhagic stroke during the 1-year in the emergency room setting under the follow-up in both groups. qualified neurologist’s evaluation. The Conclusions: In this preliminary retrospective advanced image study is CTA and CTP. If study, there was no significant difference the LVO is suspected, the transfer-protocol in the functional outcomes at 3 months and would be initiated , either radiographer for 1 year, nor in recurrent ischemic stroke CTA and CTP or no neuro-interventionist between two groups. Interestingly, there was is in the hospital. The patients were mostly no significant difference in adverse effects transferred to primary stroke center which of hemorrhagic stroke and GI bleeding located in 80km far from our hospital. The either. Further analysis with a larger sample interventionist in our hospital includes size and a longer follow-up is undergoing. cardiologist, neurosurgeon, neurologist. A randomized controlled trial to validate Results: Since 2016~2019/08, 36 LVO- the optimal antithrombotic regimens in patients were suspected. 14 LVO-patients ischemic stroke patients with large artery were transferred to primary stroke center atherosclerosis is warranted. without confirmation of CTA. 9 of 14 patients (64%) were definite LVO after CTA. 4 of 9 patients (44%) underwent EVT. 22 LVO-patients underwent CTA in ԼӴୢୢ୿ᚂ଱ݽᕛသഋσՖᆓߢ our hospital, and 18 patients (81%) wereཱི ც confirmed LVO. 5 of 18 patients were֨ޟ༬੾௉ ዞ transferred to primary stroke center forڷጰ ѠεᙴଣཥԮϩଣઓ࿶೽ EVT because lack of interventionists. 1 of 5 patients underwent EVT after transfer. 6 of The Trouble of Treating Patients with 13 patients underwent EVT in our hospital. Large Vessel Occlusion at Regional Conclusion: Time is brain. The median time Hospital in Hsinchu of door to groin puncture was longer among Kun-Chang Tsai transferred patients than not transferred Department of Neurology, National Taiwan patients (228 minutes vs 205 minutes). The University Hospital Hsin-chu Branch, Hsinchu, futile inter-hospital transfer rate for EVT Taiwan was 56%. The positive predictive rate of LVO was lower among transferred patients Background: Acute ischemic stroke (AIS) than non-transferred patients (64% vs 81%) with large vessel occlusion (LVO) is The distance between regional hospitals in critical. In regional hospitals, endovascular Hsinchu and primary stroke centers is more thrombectomy (EVT) is not always available far than other counties in Taiwan. Therefore with limitation in advanced neuroimage the time-saving for inter-hospital transfer study and resources of manpower, most is very limited. The full-time coverage of

240 ⹛㛪⢨⠘媽㕮 interventionist for EVT is a major solution the stroke lesion and the baseline brain for these LVO patients. condition. Small-vessel disease burden was decided by modified cerebral small vessel disease burden (mCSVD) and the degree of hippocampal atrophy was evaluated by ኇ჋ᏰωՖᆓ੾ᡐܖ੕଻ଟຈᕻᄇ಑ mesial temporal atrophy score (mTA). Both ΙԩીՖܒϛॳ੾௉ϛॳࡣΙԑϞᇯ scales were evaluated by the committee of ޣԢጣϞኇ៪ 3 independent readers blinded to cognitive results and the final scores of the mCSVD ۇѶǵֺᅸד׵খդǵ݅դࢅǵ᝵ች੿ǵഋ ԋεᙴଣઓ࿶೽ and mTA was given to each patient after decision-making committee. The serial data The Impact of Small Vessel Disease of cognitive results were analyzed using Burden and Hippocampal Atrophy on group-based trajectory model and the impact Cognitive Trajectory over One Year of vascular burden and hippocampal atrophy in Patients with First-Ever Ischemic was analyzed by multiple logistic regression. Stroke Results: A total of 132 patients were Kang-Po Lee, Po-Yu Lin, Hui-Chen Su, Chih- enrolled and we analyzed the data from 112 Hung Chen, Pi-Shan Sung patients who completed cognitive monitoring Department of Neurology, National Cheng-Kung for at least 2 times. Mean age was 64.9 ± University Hospital, Tainan, Taiwan 10.2 years. The median values of education level was 9 (IQR:6-12) years. The median Background: The aim of this study is of NIHSS at admission was 3 (IQR1.5-5) to investigate the impact of small-vessel points. The post-stroke cognitive trajectory disease burden and hippocampal atrophy was grouped into low/intermediate/high on post-stroke cognitive trajectory over one (group I/II/III) cognitive performance by    [ —|     \ trajectory modelling. Both improvement in Methods: This is a prospective cohort study post-stroke cognitive function was noted with serial monitoring of cognitive function over 1-year period in the intermediate and for 3 times over 1-year period after first- high cognitive performance group, but not ever ischemic stroke. The time to monitor noted in the low cognitive performance cognitive function included acute phase group. Higher dementia occurrence rate (4-7 days post stroke), subacute (3 months was found during follow-up in the low post stroke) and chronic state (1 year post performance group. The baseline vascular stroke). We enrolled patients with first- burden, instead of hippocampal atrophy, was ever ischemic stroke admitted to our stroke independently associated with higher risk ward from 2015/02 to 2018/01. The enrolled of low cognitive performance group after criteria included normal consciousness stroke (mCVSD: adjusted OR 2.74 (95% CI level without delirium, subjective memory 1.09-6.86) p = 0.032; mTA: adjusted OR 1.53 impairment or language disturbance as the (95% CI 0.56-4.21) p = 0.405), but the risk chief complaints of index stroke. Cognitive was even higher in those patients combined function was assessed by Montreal with concomitant high vascular burden and Cognitive Assessment (MoCA). Brain MRI hippocampal atrophy (Adjusted OR 6.29 were performed in acute phase to determine (95% CI1.90-20.83), p = 0.003). However,

241 ⹛㛪⢨⠘媽㕮 the stroke location, stroke etiology or stroke Background: Atrial fibrillation (AF)- severity exhibited no association with the related stroke causes severe disability and post-stroke cognitive trajectory. poor prognosis. Adjunctive statin therapy Conclusion: In our studies, cognitive has been recommended for atherosclerotic- improvement after stroke was noted in related stroke but not AF-related stroke. This patient with intermediate or high cognitive study investigated the effects of statin in AF performance, but not in low performance patients who experienced acute ischemic group, which also gave higher occurrence stroke. rate of dementia over 1-year follow-up. Methods: Data from patients with AF Stroke severity, etiology or location might experiencing first-ever ischemic stroke exert less impact in this group with small between 2001 and 2010 were collected strokes (median NIHSS at admission: from the Taiwan National Health Insurance 3 points). The impact of small-vessel Research Database and categorized into non- disease burden may somehow outweigh the statin and statin groups. The statin group was detrimental effect of hippocampal atrophy in further divided into pre-stroke statin (those post-stroke cognitive transition. who began statin therapy before stroke) and post-stroke statin (those who began statin therapy after stroke) groups. The risks for recurrent ischemic stroke, coronary artery ࢊኈΛ᜸᛾ސџ෵ЍЖܘᠬଢ଼੾Ρี disease (CAD), intracranial hemorrhage ҡࡨܒીՖܒϛॳࡣᢓϱюՖีҡ౥ (ICH), and 1-year mortality were compared .among the groups ـ1ԑԫι౥ȈѮᢊࢺ՗੾Ᏸंڷ ᄪ2ǵ஭Ўૈ1ǵᐽԋ Results: A total of 43,242 patients wereדඁᅩ1ǵጰۗ⣬1ǵ݅݅ Ꮶ1ǵጰΏЎ1 in the non-statin, 2858 in the pre-stroke .ᙴଣઓ࿶ϣࣽ statin and 4640 in poststroke statin groupsۺ1ଯ໢ߏ۪इ ύЈ Comparing the risk for recurrent stroke andز2ᖏ׉ၗૻᆶᙴᏢ಍ीࣴ CAD among the three groups, the prestrike Adjunctive Statin Therapy Reduces statin and post-stroke statin groups did not Intracranial Hemorrhage and 1-Year exhibit a significant difference compared Mortality in Patients with Atrial with the non-statin group. In terms of Fibrillation after Acute Ischemic Stroke: ICH risk, the statin group had a lower A Population-Based Epidemiological risk for ICH (odds ratio [OR] 0.79, 95% Study From Taiwan confidence interval [CI] 0.68–0.90; p = Hui-Chen Lin1, Wan-Chen Tsai1, Jr-Rung 0.0007) compared with the non-statin group. Lin2,,Wen-Neng Chang1, Cheng-Hsien Lu1, Nai- The overall 1-year mortality in both statin Wen Tsai1 subgroups was lower than that in the non- 1 Department of Neurology, Chang Gung statin group (pre-stroke statin, OR 0.55 [95% Memorial Hospital-Kaohsiung Medical Center, CI 0.49–0.61]; p < 0.0001 versus post-stroke Taoyuan, Taiwan statin, OR 0.53 [95% CI 0.48–0.58]; p < 2 Clinical Informatics and Medical Statistics 0.0001). Research Center, Chang Gung University, Conclusions: Statin therapy reduced the risk Taoyuan, Taiwan of ICH and 1-year mortality in AF patients who experienced acute ischemic stroke.

242 ⹛㛪⢨⠘媽㕮

Ȉၼڙ੾ҡ౩ᐠޟᓛଢ଼૕੕ᆭᝮᆓᡗ ϛॳࡣϛኾડငฮܒഺ༌ޟཎᜋራᛤ Ѕཐឈ੿חᇄᖝڏЅڙў׻ޟൢ֙ ଢ଼Ҫ፴ٽਰَق༈ಛသՖᆓഅኇܻ݂ ܒࣺᜰޟޑ ܴד໳ҏනǵ׵ ፁғᅽճ೽ਲ༜ᙴଣઓ࿶ϣࣽ ෯Ⴈ։1ǵ׵ߪ፣1, 2ǵᎄࡌᑫ1ǵᖴ݊ᇇ1ǵԢ ܴᄆ3ǵယធൈ1ǵᖙᏢЎ1ǵᇳ௴ຬ1 Traumatic Carotid Cavernous Fistula 1Ѡεᙴଣઓ࿶೽ ଣزDiscovered Incidentally on Conventional 2୯ৎፁғࣴ Cerebral Angiography 3໚ܴεᏢᙴπ܌ Huang Yu-Ching, Lee Chi-Ming Department of Neurology, Taoyuan Hospital, Pathophysiology of Central Poststroke Ministry of Health and Welfare, Taoyuan, Pain: Motor Cortex Disinhibition and Taiwan Its Clinical and Sensory Correlates Sung-Chun Tang1, Lukas Jyuhn-Hsiarn Lee1, 2, Carotid cavernous fistula (CCF) involves Jiann-Shing Jeng1, Sung-Tsang Hsieh1, an abnormal communication between the Ming-Chang Chiang3, Shin-Joe Yeh1, Hsueh-Wen cavernous sinus and the carotid arteries Hsueh1, Chi-Chao Chao1 presenting with clinical features. According 1 Department of Neurology, National Taiwan to literature, CCF is not an uncommon University Hospital, Taipei, Taiwan occurrence in patients involved in road 2 National Institute of Environmental Medicine traffic accident. Its pathogenesis could be Sciences, National Health Research Institutes, traumatic or spontaneous. Our patient is Taiwan a 32-year-old woman involved in a road 3 Department of Biomedical Engineering,  [   |    ¯ \ National Yang-Ming University, Taipei, Taiwan Emergency cranial CT scan revealed subarachnoid hemorrhage and suspected Background and Purpose: Central poststroke aneurysm of the left internal carotid pain (CPSP) is a disabling condition in artery. Subsequent computed tomographic stroke patients, and evidence suggests that angiography and magnetic resonance altered corticospinal and motor intracortical angiography were negative for aneurysm or excitability occurs in neuropathic pain. The CCF but a latter digital subtraction cerebral objective of this study was to investigate angiography showed florid signs of CCF changes in motor cortex excitability and (dilated cavernous sinus and left ophthalmic sensorimotor interaction and their correlates vein). Though, no clinical feature of with clinical manifestations and alterations CCF was seen in this patient. Patient was in somatosensory systems in CPSP patients. subsequently referred to another hospital, Methods: Fourteen patients with CPSP but under the condition of persistent impaired no motor weakness were compared with consciousness but lack of clinical signs, with age- and sex-matched healthy controls for a neuro-interventional radiologist for further motor cortex excitability and sensorimotor intervention and management. In conclusion, interaction assessed by transcranial this case indicates that the absence of magnetic stimulation to measure resting clinical features and negative non-invasive motor thresholds, short-interval intracortical investigation does not exclude the diagnosis inhibition, intracortical facilitation, and    | [ \ afferent inhibitions. The sensory pathway

243 ⹛㛪⢨⠘媽㕮 was evaluated by quantitative sensory ᆵчᄪ҇ᕴᙴଣៈ౛೽ testing, contact heat evoked potential, and somatosensory evoked potentials. Clinical Care of the Post Intra-Arterial pain and quality of life were assessed with Thrombectomy Patient validated tools. Ching-Wei Lin, Shu-Yuan Ho, Hui-Chi Huang, Results: The duration of CPSP was 3.3 Jui-Yao Tsai, Tzu-Ching Liu, Ying Liang ± 3.0 years (ranging 0.5-10 years), and Department of Nursing, Taipei Veterans General pain significantly impaired quality of life. Hospital, Taipei, Taiwan Compared with the unaffected hemisphere, the stroke hemisphere had higher thermal Background and Purpose: In the past 20 thresholds, lower contact heat evoked years, active treatment of acute infarction potential amplitudes, and prolonged cortical has only administered intravenous somatosensory evoked potential latencies. thrombolytic agents within 3–4.5 hours of There was no difference in resting motor gold. However, in very short time windows, thresholds between the stroke and unaffected patients who are able to receive treatment in hemisphere or between patients and a timely manner are still a minority (about controls. CPSP patients had a reduction in 2–5% of all strokes). However, if the stroke short-interval intracortical inhibition in the is a major vascular occlusion from a larger stroke hemisphere compared with that in diameter, until the success of the new intra- the unaffected hemispheres of patients and arterial mechanical thrombectomy trial in controls. No changes were noted in afferent 2015, the acute stroke treatment time will be inhibitions between the stroke and unaffected extended again. hemispheres. The short-interval intracortical Results: We retrospectively retrieved inhibition of the stroke hemisphere was patients’ data from Stroke Registry of a negatively correlated with self-rated health Northern medical center. Patients admitted on a visual analog scale and positively between 2017 and 2018 were screened. correlated with cortical somatosensory The current study recruited 129 patients. evoked potential latencies. Demographics of patients are presented in Conclusions: CPSP patients with intact Table 2. The results showed that baseline corticospinal tracts showed reduced motor characteristics were similar. At 3-months intracortical inhibition in the stroke after stroke, 44.2% of patients had better hemisphere, suggesting defective gamma- functional recovery .Our results showed that aminobutyric acid-ergic inhibition. This about half of the stroke patients improved disinhibition was associated with impaired their functional status at 3-months after quality of life and was related to dorsal stroke. column-medial lemniscus pathway Conclusions: Intravenous recombinant dysfunction. tissue plasminogen activator (IV -rtPA) remains the only approved systemic reperfusion therapy suitable for most patients presenting timely with acute ੃೚ࡣ੾ΡϞ៖౩ ischemic stroke. In recent years, intra-arterialڥ ݅ᓉᖚǵՖలൟǵ໳ᑯนǵጰྷટǵ thrombectomy (mechanical thrombectomy) ቅη๭ǵఉᑉ has emerged, and the results of randomized

244 ⹛㛪⢨⠘媽㕮 control trials have also proved its efficacy. Identification of Ischemic Stroke in This article provides an overview of MRI Using Convolutional Neural thrombectomy, the management of patients Network with Deep Learning with an acute ischemic stroke eligible for Meng- Zong Tsai1, Syu-Jyun Peng2, Yu-Wei this procedure and the implications for Chen3, Kuo-Wei Wang3, Ye-Lin Guo3, Jang-Zern nursing practice in Taipei Veterans General Tsai1 Hospital. A new treatment has started to 1 National Central University, redefine acute stroke care in countries 2 Taipei Medical University, all over the world –thrombectomy. Early 3 Landseed International Hospital treatment is critical to rescue potentially salvageable tissue. Safe, rapid and effective Background and Purpose: Infarct detection arterial recanalization to restore blood flow on cerebral MRI have been hindered by and improve a functional outcome remains the histographic overlapping of image the primary goal of hyperacute ischemic artifacts and infarct lesions. This study stroke management. Post-thrombectomy aimed at improving the detection accuracy management of the emergent large vessel by utilizing convolutional neural network occlusions patient is complex. Vital aspects trained by deep learning algorithm. of patient care that require monitoring Methods: The preprocess included the and treatment include optimization of \ Œ œ     ©  ° reperfusion, post-reperfusion hemorrhage, Second, registration of DWI to T1W; Third, cerebral edema, access site complications, registration of ADC to DWI; Fourth, z-axis and rehabilitation efforts. Careful attention registration of ADC to DWI; Fifth, skull to these aspects is vital to outcome masking; Sixth, intensity normalization of optimization. Nurses must keep up with the the cerebellar portion of excessive intensity; times and be active. Take the initiative to Seventh, removing DWI/ADC pixels with learn new guidelines, update concepts in below-/above-threshold intensity. real time, challenge higher standards, and The CNN structure contained four dynamically masterstrokes. New progress in convolutional layers that had 16, 32, 64 and diagnosis and treatment, providing evidence- [   ©&\› |      based support for nursing decision-making was followed by a batch normalization layer, and implementation of ischemic stroke. a ReLU layer, max pooling 2d layer. The Reducing the complications and length of       [       stays of stroke patients, and improving the by a fully connected layer and a softmax quality of life of stroke. layer. The network model was trained with deep learning using the stochastic gradient descent algorithm. The activation function அܻ౏࡙ᏰಬϞఠ༬ܒϛॳᆄਏഅኇ ReLU was used for faster convergence and ᒱᜋ    [  \•     .1ǵ൹৪໋2ǵഋѓጎ3ǵЦ୯଻3ǵ weights were initialized randomlyےۏጰ ೾ယᐴ3ǵጰകϘ1 An experiment to evaluate the developed 1୯ҥύѧεᏢǵ2ѠчᙴᏢεᏢǵ3ᖄཥ୯ሞ CNN involed 15 stroke patients and 15 ᙴଣ healthy persons. The cerebral infarcts and

245 ⹛㛪⢨⠘媽㕮 artifacts of the patients had been segmented Methods: We performed a single center by an experienced neurologist. Patches of retrospective analysis of consecutive }&} š      patients with AIS due to acute occlusion subject MRIs. The training set consisted of of extracranial ICA, who underwent 90% of the patches and the rest were used as thrombectomy with or without carotid stent the test set. placement. The outcomes were evaluated Results: The experimental result shows based on rate of angiographic recanalization a similarity index of the developed CNN " [•! „   | infarct detector exceeds 90%. Moreover, of NIHSS score, modified Rankin Scale the required detection time to finish the (mRS) at discharge and after 3 months, detection is just one third of that of the and symptomatic cerebral hemorrhagic conventional automated method. complications. Conclusion: Our deep learning algorithm Results: From October 2014 to Feb. 2019, incorporates location information, whole 43 consecutive thrombectomy procedure brain intensity, slice intensity, and slice order with extracranial artery stenosis. Nine (21%) to better exploit the infarct features. The cases was failed to access the occluded performance of this new design is better than lesion due to complete proximal occlusion. conventional infarct detection algorithm. In the rest of 34 cases with complete endovascular procedures, 76% are men, with median age 65 years (IQR 59-74). The median NIHSS at presentation was 19 IQR 59-74). In 21 patients, there was an) ܒငଢ଼૕ݽᕛᢓѴϱᓛଢ଼૕ߢ༬Ϟࡨ ીՖܒသϛॳ additional intracranial occlusion (tandem ᝄᝊയ1ǵ໳हྼ2 lesions) at distal ICA and M1. Intracranial 1ύ୯ᙴᛰεᏢߕ೛ᙴଣܫ৔೽ǵ2ύ୯ᙴᛰε occlusions were either treated mainly Ꮲߕ೛ᙴଣઓ࿶೽ with combined stentreiver and aspiration technique. 82% cases achieved successful Endovascular Treatment of Extracranial revascularization (TICI>= 2b). Among the Internal Carotid Artery Occlusions in cases (n = 14) with carotid stent deployment Acute Ischemic Stroke in hyperacute phase, 3 (21%) patients had Pao-Sheng Yen1, Hung-Yu Huang2 mRS<3 at day 90. Symptomatic intracranial 1Radiology Department, 2Neurology Department, hemorrhage (sICH) was found in 6 patients China Medical University Hospital, Taichung, (18%). The mortality rate was 6% at 90 Taiwan days. Conclusion: Endovascular treatment of Purpose: Acute ischemic stroke (AIS) due acute ICA occlusion appears to have a high- to acute occlusion of the extracranial internal recanalization rate in our cohort of patients carotid artery (ICA) is associated with a with acute ICA occlusion. Future prospective   [  |       \ studies are necessary to determine which The purpose of this study is to demonstrate      [   the technical success of endovascular form of therapy.      [    outcome in this unique stroke population.

246 ⹛㛪⢨⠘媽㕮

ϛॳᄇҡࣀࠢ፴Ѕю଱Ԋညޟኇ៪ information for enhancing the quality of ઔ1ǵ݅ችী2 health care and for managing the secondaryذ؇ 1ଯ໢ᄪ҇ᕴᙴଣ health problems faced by stroke survivors. ऍᙴᏢύЈ These prospective domestic data would beڻ2 particularly valuable for inter-regional and The Influence of Quality of Life and international comparisons, as well as for Discharge state-level policy making. Hsiu-Chu Shen1, Huey-Juan Lin2 Methods: We will conduct a one-year 1Kaohsiung Veterans General Hospital prospective cohort study by enrolling 2Chi-Mei Medical Center   |   [ —|     stroke in the Chi-Mei Medical Center. Background & Purpose: While diagnostic Participants will be evaluated via assessment tools and medical treatment have advanced survey questionnaires by face-to-face or considerably, stroke is widely considered a telephone interviews at acute ward, and 1, 3, catastrophic event with long-term physical, 6 months after stroke. psychological, and social consequences. The Goals: We expect to assess the short-term burden of stroke is likely to increase, as a and long-term needs and newly developing consequence of the rapidly aging population secondary health problems in stroke and a better survival rate of stroke. However, survivors. These prospective domestic the provision of chronically continuing data will be of great value for setting up a services for patients is typically limited by comprehensive multidisciplinary team care the lack of robust estimates of long-term  |   \   needs after the stroke event. Specifically, interventions on the long-term consequences less attention has been paid to the long-term of stroke, as well as for providing burden and related needs for health care. Our implications for health policy makers. study would contribute to extant research by proposing various strategies for clinical Keywords: ischemic stroke, prognosis, management, accessing specialized care, and quality of life, needs assessment, subacute organizing in-hospital stroke care. Moreover, care, long-term care. our proprietary data would provide useful

247 ȁȁᓃןരȁȁ ȁȁᓃןരȁȁ ȶѮᢊϛॳᚂᇬȷ׹ገᙏࠌ

1. ↉冯ᷕ桐慓⬠䚠斄ᷳ⬠埻婾叿烉⊭㊔㊯⺽ˣ䵄婾ˣ⍇叿ˣ䕭ἳ⟙⏲ˣ⮰柴⟙⮶ㆾ℞Ṿ⟙⏲炻㛒 㚦↲庱㕤⚳ℏ⢾℞Ṿ↲䈑侭⛯䁢㛔娴↲庱ᷳ⮵尉ˤ 2. ㈽䧧㗪炻婳⎴㗪旬ᶲ农㛔娴䓛婳㈽䧧倚㖶㚠炻堐㖶㈽䧧㛔娴ᷳシ栀⍲℞↲䘣㕡⺷炻᷎旬↥婒㖶 ㇨㚱叿侭⛯㚦忶䚖᷎䯥⎵⎴シˤ 3. Ṣ橼娎槿ˣṢ栆䞼䨞枰㚱ΐ䎮⥼⒉㚫ᷳ⎴シ炻≽䈑娎槿⽭枰㚱≽䈑⥼⒉㚫ᷳ⎴シˤ䞼䨞⮵尉➢ 㕤Ṣ㪲ᾅ嬟炻暨䴻 IRB炷Institutional Review Board炸㟠Ⅾˤ㬌⢾㔯㛓⽭枰姣㖶㗗⏎㚱㍍⍿ảỽἮ 㸸ᷳ岲≑炷financial disclosure炸炻ẍ⍲⇑䙲堅䨩炷conflict of interest炸䫱ˤ 4. Ἦ䧧ᶵ㊀ᷕ㔯ㆾ劙㔯炻㔯䧧婳ẍ A4 ⣏⮷炻㨓㚠䶐㌺炻᷎⮯枩䡤㧁䣢㕤㬋ᶳ㕡炻埴冯埴攻䨢ℑ埴 (double-spaced)ˤᷕ㔯䧧⼴旬劙㔯㐀天嬗㔯炻劙㔯䧧⼴旬ᷕ㔯㐀天嬗㔯炻ᷕˣ劙㔯㐀天ℏ⭡暨⮵ 䄏ᶨ农炻ᷕ㔯䧧ᷕ⣦姣ᷳ劙㔯昌⮰㚱⎵娆⢾ᶨ⼳⮷⮓ˤ 5. ⍇叿婾㔯㊱烉㐀天ˣ⇵妨ˣ㛸㕁冯㕡㱽ˣ䳸㝄ˣ妶婾ˣ娴嫅ˣ⍫侫㔯䌣ˣ旬堐ˣ⚾䇯婒㖶枮⸷ 㑘⮓ˤ䕭ἳ⟙⏲⇯㊱烉㐀天ˣ⇵妨ˣ䕭ἳˣ妶婾ˣ⍫侫㔯䌣ˣ旬堐ˣ⚾䇯婒㖶枮⸷㑘⮓ˤ䵄婒 ⍲⮰柴⟙⮶ᶵ⽭㊱㬌㟤⺷㑘⮓炻Ữ⽭枰↿↢㐀天ˣ⍫侫㔯䌣⍲㐀天嬗㔯ˤ 6. ᷕˣ劙㔯㐀天⼴暨旬斄挝娆炷 Key words炸炻军⣂ 6 ᾳˤ 7. 旬堐炻㭷ᶨ堐㟤暨㚱ᶨ䯉䞕㧁柴炻ℏ⭡⃀⎗傥ἧ䓐ᷕ㔯⽭天㗪⼿ᷕˣ劙㔯᷎↿烊堐㟤ᷕ⊧䓐䷙ 䶂炻㨓䶂ḇ䚉⎗傥性⃵ˤ⚾䇯婳䚉慷㍸ὃ暣⫸㨼炻妋㜸⹎军⮹䁢 300 ⁷䳈炷dpi炸炻⚾䇯㟤⺷䁢 JPG 㨼ˤ⚾婒㖶ẍᷕ㔯䁢旸炻⃀慷䯉㻼ˤ 8. ⺽䓐ṾṢᷳ堐㟤ㆾ⚾䣢枰⽝⼿叿ἄ㪲㇨㚱Ṣ⎴シ炻⏎⇯娚⚾堐ᶵḰ↲䘣ˤ劍ἧ䓐⶚䘤堐䘬⚾䇯 堐忼㤪⾝侭炻ἄ侭暨慵㕘墥ἄ旬⚾ᶼ性⃵Ὕ䉗䇰㪲炻⽭天㗪ἄ侭⽭枰䯥䳸⽭天㔯ẞ炻ẍ屈⬴ℐ 㱽⼳屔ảˤ 9. ⮩朊枩屯㕁烉⊭㊔婾㔯Ⱄ⿏ˣ㧁柴ˣἄ侭⥻⎵ˣả借╖ỵ炻⍲㈽䧧侭冯忂妲ἄ侭ᷳ倗䴉暣娙 炷⏓ㇳ㨇炸ˣ忂妲⛘⛨ˣ暣⫸悝ẞᾉ䭙䫱屯㕁炻ẍ㕡ὧ倗䴉ˤ 10. ⍫侫㔯䌣烉㔯ᷕ⺽䓐⍫侫㔯䌣㊱⃰⼴枮⸷炻ẍ旧㉱ỗ㔠⫿㍉⎛ᶲ㧁䣢㱽烊⺽䓐䚠忋䭯㔠 3 䭯 炷⏓炸ẍᶲ炻℞嘇㔠ẍ忋嘇忋ᷳ炻⤪ 1, 3-5ˤ⍫侫㔯䌣㚠⮓㕡⺷婳⍫䄏Index Medicus炻暄娴炼叿 侭⥻炷ℐ炸⎵炷䷖炸烉柴䚖ˤ暄娴⎵ˣ⸜ấˣ⌟ˣ崟彬枩㔠ˤ叿侭 6 Ṣ炷⏓炸ẍᶳ炻㇨㚱叿侭 ℐ↿烊叿侭 7 Ṣẍᶲ炻⇯↿↢⇵ 3 Ṣ炻⼴朊≈ “ et al ” ㆾ “ 䫱 ” 堐䣢ᷳˤ䭬ἳ⤪ᶳ烉 (1) Hsieh FI, Lien LM, Chen ST, et al. AHA/ASA Get With The Guidelines – stroke performance indicators: surveillance of stroke care in the Taiwan Stroke Registry. Circulation 2010;122:1116- 1123. doi: 10.1161/CIRCULATIONAHA.110.936526. (2) Tsai HH, Pasi M, Tsai LK, et al. Distribution of lacunar Infarcts in Asians with intracerebral hemorrhage: an MRI and amyloid PET study. Stroke 2018;49:1515-1517. doi: 10.1161/ STROKEAHA.118.021539. (3) Chung CP. Types of stroke and their differential diagnosis. In: Caplan LR, Biller J, Leary MC, Lo EH, Thomas AJ, Yenari M, Zhang JH, eds. Primer on Cerebrovasculasr Diseases, 2nd ed. London, United Kingdom, Academic Press, 2017:372-376. (4) 㸗枴⏃ˣ惕⺢冰ˣ⹾㻊㔯ˣ檀㖶夳烉⿍⿏仢埨⿏儎ᷕ桐㱣䗪䘬㚨㕘䘤⯽ˤ⎘䀋慓䓴 2017;60: 178-181ˤ 11. Ἦ䧧ᶨ䴻↲庱炻䇰㪲Ⱄ㛔㚫㇨㚱炻㛒䴻㚠朊⎴シ炻ᶵ⼿ẍảỽ㕡⺷廱庱ˤ㟉⮵䓙叿侭屈屔⇅ 㟉炻㟉⮵㗪婳性⃵⛐⍇䧧ᷕ徥≈⫿⎍ㆾ⣏ⷭᾖ㓡ˤ ȶѮᢊϛॳᚂᇬȷ׹ገᖐ݂ਪ

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