AlexeyP rotopopov IC-2017– arch9th 2017 Some facts about Stroke in Russian Federation

Population 144,6 millions

Neurovascular death rate 299 493 (15,7%)

Oncological death rate 291 819 (15,3%)

 550 000 new strokesperyear(3,803 per1 m illionperyear)  2nd placeincardiovasculardeathrate  2nd placeinoverallmortality  1st placeamongthecausesofdisability  theannualdeathratefrom strokeinR ussiaisoneofthehighestinthew orld  only20% ofpatientsreturntow ork

 thetotalcosts- upto22 billions$annually Skvortsova ., Stakhovskaya ., 2009, 2014

Ministry of Healthcare, 2017

Central statistical data base, 2014 Some facts about Stroke in USA

 5th leadingcauseofdeath intheU nitedS tates  killingm orethan130,000 Am ericanseachyear- that’s1 ofevery20 deaths.  omeoneintheU nited S tateshasastrokeevery 40 seconds.Everyfour m inutes,someonediesof stroke  795,000 peopleinthe U nitedS tateshaveastroke (app.2,500 permillion)  610,000 ofthesearefirstor new strokes  185,000 arerecurrent strokes  S trokereducesmobility in m orethanhalfofstroke survivorsage65andover en tersforD isease C on trolan P reven tion ,Nation alC en terforH ealthStatistics.Un d erlyin C ause of D eath1 999-201 3on C D C ND ER O lin D atabase,released 201 5.Dataarefrom the M ultipleC ause of D eathFiles,1999-201 3,ascom piled from d ata provid ed by the 57 vitalstatisticsjurisdiction sthrough the VitalStatisticsCooperative P rogram : ttp://w on d er.cd c.gov/ucd -  S trokecoststhenation$33 icd 1 0.html.A ccessed on Feb 3,201 5.

billionannually M ozzafarian D , en jam in EJ,Go A S,etal.on beh alfof the A m erican H eartAssociation StatisticsC om m ittee an d Stroke Statistics Subcom m ittee.H eartdisease an d stroke statistics—201 6upd ate: a reportfrom the A m erican H eartAssociation .C irculation . 201 6;133:e38-e360. Epidemiology of Stroke

Russia Czech Republic Germany

3803 strokes per 2394 strokes per 2455 strokes per 1 million/year 1 million/year 1 million/year

KrogiasC .etal.Tren d sof (M in istry of H ealthcare, W id im sky P.,IC C A -2016, P rague,23/04/2016 h ospitalized acutestroke care 2017 ) in German (…) Journalof the Neurological Scien ces345(2014)202–208 Negative dynamics of Stroke epidemiology in Russia

T otalnum berofallstrokes(peryear) 560000 549970 550000 540000 534245 535549 530000 523263 520000 514869 510000 504577 500000 490000 480000 2010 2011 2012 2013 2014 2016

Ministry of Healthcare, 2017 Acutecoronarysyndromevs.S trokeinR ussia (thetotalamountofinterventionsandestimatedneed)

ACS S troke

Incidenceperyear 520 524 550 000

Koncevaya A, 2011 Skvortsova V., Stakhovskaya L., 2009, 2014 N um berofpercutaneous 97879 -ACS < 100 interventions 46356-ST EM I Bokeria L, Alekyan B., 2016 N ecessaryamountofprocedures 214 500 -ACS 72 600 85800 -ST EM I Based on S tentforlifedata 13,2% of total Stroke number – based on incidence of LVO

Currentstatus 45,6% -ACS < 0,2% 54,0% -ST EM I Un til2016the n um berof A IS in terven tion sw asin feriorto the totalam oun tof coron aryin terven tion s in 1000 times

Th e effective treatmen tmetless than 0,2% of needed amount How manypatientsshouldreceivereperfusiontherapy inacuteischemicstroke?

Catheterbasedtherapyofacutestroke: Currentevidence. P .W idimsky,2016 100% pts with acute stroke

85% ischemic stroke 15% hemorrhagic pts stroke pts.

45% pts with a minor 40% pts with moderate stroke or TIA: or large ischemic stroke reperfusion therapy not indicated (risks outweight benefits)

10% pts.presenting w ithin<4,5hoursof 30% pts. presenting symptom onset: late: reperfusion reperfusiontherapy therapy not indicated Dynamics of the main indicators of the stroke services in Russia in 2010-2015

T otal P atients T heproportionofpatients num ber hospitalized w ithin4,5 Year w ithstrokein IV-rtP A within ofstrokes hours 24 hours, IV-rtPA, thefirst24 4,5 peryear hours % % hours, %

504 557 2010 288 618 150 337 6361 57,2 29,8 1,3

514U pto33,7% 869 2011 311 ofpatientsareadmittedtohospital 496 168 779 5914 60,5 32,4 1,1

534 245 2012 340 848w ithin4,5hours 181 947 7268 63,8 34,1 1,4

523 263 2013 344 830 174 983 7107 65,9 33,5 1,4

535549 2014 346500 174 972 7978 64,9 32,7 1,5

549 970 2015 367380 185285 10631 66,8 33,7 1,9 How manypatientsshouldreceivereperfusiontherapy inacuteischemicstrokeinR ussia(per1million/year)?

Catheterbasedtherapyofacutestroke: Currentevidence. P .W idimsky,2016 100% pts with 3803acute stroke acute Assessmentoftheproper strokecases amountofAIS interventions inR ussia

85% ischemic stroke 15% hemorrhagic 2232pts pts.w ith stroke pts. AIS

45% pts with a minor stroke or TIA: 40%1521 pts with pts.w moderate ith reperfusion therapy not basedon or large ischemic stroke m oderateor indicated (risks current outweight benefits) statistics largeAIS

13,2% 502pts.presenting pts. 26,8% pts. presenting w ithin<4,5hoursof presentingw ithin late: reperfusion symptom onset: therapy not indicated <4,5h.ofsymptomreperfusiontherapy onset P ossiblecausesof the low am oun tof in terven tion al treatmen tof acuteisch em ic stroke

Complex multi-stage logistics and interdisciplinary interaction

A small number of eligible patients = lack of trained personnel

Delays in the logistics and in the treatment decisions

Complex pharmacotherapy including high risk of intracranial bleeding complications

The narrow therapeutic window (when treatment can be effective and safe)

Technology of the procedure

Lack of specialists able to perform endovascular procedures Im pactof geograph icalfactorson the d evelopm en tan d fun ction in g of stroke caresystem

Russia is a huge country with very low population density Population:144554993people Land area:17 125191 sq.km (11 time zones) Density:8,6 persons per sq. km of land area For example…

Germany Krasnoyarsk region

Population:8 2 17 57 00 Population:2 8 7 57 90 Land area:357 021 sq.km 6 = Land area:2 3397 00 sq.km Density:230 persons persq. Density:1,22 persons persq.km of km of lan d area lan d area

2455 strokes per 1 mln/year 3100 strokes per 1 mln/year B ackgroun d of successfuldevelopm en tof the stroke caresystem in Russia

The evidence base for mechanical thrombectomy using the latest generation of stents retrievers

The highest class of recommendations and level of evidence

Availability of the latest generation of stents retrievers in Russia

The presence of the advanced STEMI network which can become the platform for the endovascular treatment of AIS in 24/7/365 regimen T heevidencebaseofreperfusiontherapyinacute ischemicstroke T hepossibilitiesandlimitationsofthrombolytictherapy rtPA vs.placebo M eta-analysisof12 CT s

T hrombolysissignificantlyimprovetreatment outcomesinacuteischemicstroke T hepossibilitiesandlimitationsofthrombolytictherapy rtPA vs.placebo M eta-analysisof12 R CT s

T hrombolysisincreasesearlymortality(upto7days)duetothe 7,7% riskofintracranialbleeding T hepossibilitiesandlimitationsofthrombolytictherapy rtPA vs.placebo M eta-analysisof12 R CT s

T hrombolysisiseffectiveinthefirst3 hoursfrom thesymptoms onset T hrombolysisalonem aynotbeenoughforeffective treatment n

o The large clot reduces i t a

the likelihood of i l a

n recanalization a c e r

o

y t i l i b a b o r p

e Clot> 8m m h T 0% ofrecanalization

T hethrombusdiameter(mm )

R iedeletal.S troke2011,42:1775-1777 The evolution of technology and the evidence base of endovascular treatment of stroke (S troke2015 46:909-914) T heevidencebaseformechanicalthrombectomyin2013

3 RCTs comparing thrombolysis and endovascular thrombectomy demonstrated nosignificantdifferencesintheresults:

IM S III S YN T HESISEXP AN S ION MR R ESCU E T heevidencebaseformechanicalthrombectomyin2013

IMS III SYNTHESIS MR RESCUE (N=629) (N=362) (N=118)

Primary intervention Selective thrombolysis O utdated MERCI MERCI / device or clot fragmentation technology LVO (ICA, M1): 33% 34% 81% Successful recanalization (TICI 44% n/a 27% 2b/3):

Good clinical 43% 42% 13% outcome (mRS 0-2):

Симптоматичное внутримозговое 6% 6% 5% кровоизлияние:

Смерть (90 день): 19% 8% 19% T heevidencebaseformechanicalthrombectomyin2013

IMS III SYNTHESIS MR RESCUE (N=629) (N=362) (N=118)

Primary intervention Selective thrombolysis MERCI MERCI / device or clot fragmentation L ow num ber LVO (ICA, M1): 33% 34% 81% ofconfirmedLVO s Successful recanalization (TICI 44% n/a 27% 2b/3):

Good clinical 43% 42% 13% outcome (mRS 0-2):

Симптоматичное внутримозговое 6% 6% 5% кровоизлияние:

Смерть (90 день): 19% 8% 19% T heevidencebaseformechanicalthrombectomyin2013

IMS III SYNTHESIS MR RESCUE (N=629) (N=362) (N=118)

Primary intervention Selective thrombolysis MERCI MERCI / device or clot fragmentation

LVO (ICA, M1): 33% 34% 81% Successful S uccessful recanalization (TICI 44% n/a 27% recanalization 2b/3): ratew aslow Good clinical 43% 42% 13% outcome (mRS 0-2):

Симптоматичное внутримозговое 6% 6% 5% кровоизлияние:

Смерть (90 день): 19% 8% 19% R ecentadvancesofendovasculartreatmenthave ledto:

-thehigherfrequencyofsuccessfulrecanalization - significantreductionintheproceduralduration

DingD.,Endovascularmechanicalthrombectomy foracuteischemicstroke:anew standardofcare. JournalofS troke2015;17(2):123-126 The evidence base for mechanical thrombectomy in 2015 5largerandomizedtrialsofmechanical thrombectomy publishedin T heN ew EnglandJournalofM edicine in2015

T ICI2b/3 m R S 0-2at90 Deathrate rate days MR CLEAN 59% 32.6% v. 19.1% 21% v 22%

ESCAPE 72% 53% v. 29% 10% v. 19%

EXTEND-IA 86% 71% v. 40% 9% v. 20%

SWIFT PRIME 88% 60% v. 36% 9% v. 12%

REVASCAT 66% 44% v 28% 18% v 16% The negative results in 2013

- O utdatedtechnology - L ow num berofconfirmedL VO s - S uccessfulrecanalizationratew aslow

mRS 0-2 after 90 days Meta-analysis of 5 randomized clinical trials in 2015 - T heuseofstentsretrievers - Confirmationoflargevesselocclusion - T hegrowthofsuccessfulrecanalizationandclinicalsuccess

mRS 0-2 after 90 days Revascularization within 24 hours m R S 0-2after90 days

Ferrante et al , Eurointervention, in press Symptomatic intracranial hemorrhage O verallmortality

Ferrante, … Reimers, Eurointervention, in press

Backgroundofsuccessin2015 Applicationofadvancedtechnologies-stentsretrievers

T rial % ofthrombectomyusingstents retrievers MR CLEAN 97 ESCAPE 86 REVASCAT 100 SWIFT PRIME 100 EXTEND IA 100 Advancedneuroimagingprotocols - to confirm the large vessel occlusion - to evaluate the perfusion and volume of penumbra S um m arizedresultsof5R CT s the number of patients assessed by the modified Rankin Scale (mRS) 0-2 pointsafter90 days

EXTEND-IA 71% (n=74) 40% ESCAPE 53% (n=316) 29% SWIFT-PRIME 60% (n=196) 36% REVASCAT 44% (n=206) 28% MR CLEAN 31% (n=500) 19%

0% 10% 20% 30% 40% 50% 60% 70% 80% Mechanical thrombectomy ± IV-tPA Optimal medication ± IV-tPA or IV-tPA alone

Philip M. Meyers, Stroke Trials: Results, Analysis and Implications. TCT 2015 Ding D., Journal of Stroke 2015;17(2):123-126 Proven safety of mechanical thrombectomy

20% 18% Symptomatic intracranial hemorrhage 16% 14% 12% No difference in the risk of 10% 8% hemorrhagic complications 8% 6% 6% 6% 3% 4% 4% 2% 2% 3% 2% 0% 0% 0% MR CLEAN REVASCAT SWIFT-PRIME ESCAPE EXTEND-IA (n=500) (n=206) (n=196) (n=316) (n=74)

Mechanical thrombectomy ± IV-tPA Optimal medication ± IV-tPA or IV-tPA alone

Philip M. Meyers, Stroke Trials: Results, Analysis and Implications. TCT 2015 Ding D., Journal of Stroke 2015;17(2):123-126 R ecoveryfrom acuteischemicstroke

60

50 48%

40 M edicationonly

30% 30 T hrombolysisalone

20 S tents-retrievers 15% (± IV-rtPA) 10

0 mRS 0-2

P .W idimsky.S T EM I-likenetworkforacutestrokem anagement?EuroP CR 2015 13,2% of patients with acute stroke are candidates for thrombectomy - 72 600 patients per year in Russia

P atientswiththecompleterecoveryexpectancy T heproperamountofthrombectomiesisnotonlythesavedlivesbutleadstoalmostdependingonthew ayoftreatment completerecoveryupto34,8thousandpatientsw hosufferedseverestroke 30000 M edicationonly* 25000 T he difference34848 IV-rtPA*

20000 ExpectednumberoffullyrecoveredpatientsreceivedM echanical thrombectomy** 15000 thrombectomy is 21780 10000 3,2timeshigherthaninconservativetreatmentgroup & * P .W idimsky.S T EM I-likenetworkforacutestroke 5000 108901,6timeshigherthaninIV-rtPAm anagement?EuroP group CR 2015 ** O samaO .,Zaidat,M D,etal.T revoacute ischemicstrokethrombectomy registry. 0 P resentedatS VIN inN ov.2015. T hrombectomy± T hrombolysis(IV-tPA) since2015 Standard treatment of acute ischemic stroke caused by large vessel occlusion R ecomm endationclassI Level of evidence А Approved onApril16th 2015

Standard (A) Stents retrievers (such as Solitaire or Trevo) are recommended to perform endovascular thrombectomy Option (C) Other devices for endovascular thrombectomy can be used by decision of the specialist performing the procedure if this device provides the fast, complete and safe revascularization in the affected artery Recommendation (B) Endovascular thrombectomy should be performed by trained specialists having experience in endovascular procedures on intracranial vessels Rapid Increase in Endovascular Thrombectomy for Acute Ischemic Stroke in the United States: Data From Get With the Guidelines-Stroke T hestrategyofbuildinganddevelopingofacute strokecaresystem inR ussia By the decision of the Government of the Russian Federation ineachofthe85 R ussianregionsfrom 2008to2012 120 vascular centers were created equipped with cathlabs for the treatment of pts w ithACS andacutestroke. Cathlabs are located so that pts could be transported to these centers within 45- 90 min from 348 centers without departments of interventional cardiology. IntheR ussianFederationin2015295centersofendovascular diagnosticsandtreatmentand472 cathlabshavebeen functioning,inw hich1551 specialistshavebeenw orking

S ow how illbeengagedinAIS interventionaltreatment:

N euroradiologistsorInterventionalCardiologists?

W hat’sthecurrentstatusinthesespecialtieswehaveinR ussiatoday? N um berofP CIintheR F2006-2015

153979 27899 (22.1%) 160000

140000 126080 120000

100000 90335 75378 80000 62329 60000 51680 41425 40000 28159 32519 20267 20000

0 2006 2007 2008 2009 2010 2011 2012 2013 2014 2015 n=100 n=125 n=118 n=134 n=149 n=162 n=169 n=185 n=244 n=264 n – number of centers

S uchincreaseofP CIproceduresisconnectedw iththeN ationalP rogram w hichis completelycoveredbytheR ussianGovernment

Bockeria L., Alekyan B., 2016 N umberofpatientswithACS treatedwithP CI 2006-2015

T otalPCI– 153979 AcuteCoronaryS yndrome– 97879 (63,5%): - STEMI – 46356 (47,3 %) - nSTEMI – 24824 (25,3 %) - Unstable Angina – 26699 (27,4 %) 30358 (45 %)

100000 97879 90000 80000 67521 70000 60000

50000 41136 40000 33600 25003 30000 21138 17513 20000 12781 9488 10000 6573 0 2006 2007 2008 2009 2010 2011 2012 2013 2014 2015 n=85 n=94 n=107 n=122 n=138 n=150 n=162 n=171 n=228 n=252 n – number of centers

Beginningfrom 2015allexpenseswithACS ptsarecoveredbytheFederalInsuranceFund

Bockeria L., Alekyan B., 2016 N eurointerventionalcareisdevelopingbutthetotalnum ber ofspecializedunitsandtrainedphysiciansisnotenoughto covertheneedsforAISprogram O nly4 centersin4 cities (M oscow,St.P etersburg,N ovosibirsk,Stavropol)

aredoing m orethan100 neurointerventions onintracranialsegmentofcerebralarteries

andoverallnum berin2015of neurointerventionswas2097 onintracranialsegmentofcerebralarteries W hatkindofspecializationdow eneedforAIStreatment? IsitpossibletoinvolvetheinterventionalcardiologistsinAIS treatment?

There is one universal specialization in Russia that allows to perform endovascular procedures:

“ S pecialistinendovasculardiagnosticsandtreatment”

This specialist is allowed to perform all types of endovascular interventions S ummary: What are the opportunities of early AIS treatment in Russia? • 112 regional & 248 primary cardiovascular centers and other specialized clinics • Huge experience of emergent percutaneous ACS & AMI intervention • TheInterventionalcardiologistsinR wide availability of vascular centers that ussiaaregoingto perform ACS & AMI interventionsstarttreatinganAcuteIschemicS in 24/7 regimen (STEMI networks) troke • Advanced logistics (fast-track algorithm) in centers working with ACS (STEMI networks) • The limited availability of interventional neuroradiologists • The AIS training for specialists who perform AMI procedures takes less time than training of interventional neuroradiologists from the beginning Petr Widimsky, Charles University Prague. EuroPCR 2015 (with some changes and additions) Regions in Russia actively developing the acute ischemic stroke care system for today

Region Stroke rate (thousands / million / year)

Moscow 2,95

Rosstat201 4

St. Petersburg 5,0

Spb d epartmen tof H ealthcare 201 2

Krasnodar Region 3,0 Tsukurova L,Esipen ko N,201 2

Krasnoyarsk 3,1 Region n yakin P .etal,201 5

Kemerovo Region 2,4 Kovalen ko A ,Gileva O .2008

Khanty-Mansiysk 2,24 – Yugra Region Lebedev I,2011 Regions of Russia actively developing interventional care in acute ischemic stroke at the beginning of 2017 Development of regional stroke networks to ensure the optimal patients logistics

Moscow Kh-M - Yugra

St. Petersburg

KemerovoKrasnoyarsk Region Region

Krasnodar Region Planned amount of mechanical thrombectomies in accordance with the performance of the leading countries

Countries leading in AIS Region of Russia Planned Rationale treatment (peryear) (per1 m illion )

Germany (2012) Moscow 600 50

48 procedure/million/year St. Petersburg 200 40 KrogiasC .etal.Tren d sof h ospitalized acutestroke care in German y (…) Journalof the NeurologicalScien ces345(2014)202–208

Krasnodar Region Germany (2014) 250 45

70 procedure/million/year

W id im sky P .,IC C A -2016,P rague,23/04/2016 Krasnoyarsk Region 100 35

Czech Republic (2014) Kemerovo Region 50 20 54 procedure/million/year

Khanty-Mansiysk – 80 50 W id im sky P .,IC C A -2016,P rague,23/04/2016 Yugra Region Face S troke A rm S peech T est P atientlogistics < 4,5hours

Availabilityofendovascular treatmentw ithin30 m in 4,5– 6hours no yes

GCS 12-15 IV-rtPA N IHS S 0-25 AS P ECT 6-10 yes yes no

successful unsuccessfulor Endovascular contraindicated yes no treatment

Intensivecareunit S trokeunit T hem ostdiscussedquestionsfortoday

 T heimplementationofendovascularAIS treatment technologyintheexistingAM I/ACS centers

 Discussionofthem ultidisciplinaryapproachtothetreatment ofAISbefore,duringandaftertheendovascular thrombectomy

 Hospitalizationofproperlyselectedpatientattherighttime andintherightplaceisstillthem ostimportantandreally challengingtask ICCA STROKE 2017 | March 24-25th 2017