Therapeutic Endoscopy-Related GI Bleeding and Thromboembolic
Total Page:16
File Type:pdf, Size:1020Kb
Gut Online First, published on September 5, 2017 as 10.1136/gutjnl-2017-313999 Endoscopy ORIGINAL ARTICLE Gut: first published as 10.1136/gutjnl-2017-313999 on 5 September 2017. Downloaded from Therapeutic endoscopy-related GI bleeding and thromboembolic events in patients using warfarin or direct oral anticoagulants: results from a large nationwide database analysis Naoyoshi Nagata,1 Hideo Yasunaga,2 Hiroki Matsui,2 Kiyohide Fushimi,3 Kazuhiro Watanabe,1 Junichi Akiyama,1 Naomi Uemura,4 Ryota Niikura5 1Department of ABSTRACT Gastroenterology and Objective To compare the risks of postendoscopy Significance of this study Hepatology, National Center outcomes associated with warfarin with direct oral for Global health and Medicine, What is already known on this subject? Tokyo, Japan anticoagulants (DOACs), taking into account heparin 2Department of Clinical bridging and various types of endoscopic procedures. ► Oral anticoagulant users have a higher risk Epidemiology and Health Design Using the Japanese Diagnosis Procedure of GI bleeding after therapeutic endoscopy, Economics, School of Public Combination database, we identified 16 977 patients whereas temporal discontinuation of oral Health, The University of Tokyo, anticoagulants may increase their risk of Tokyo, Japan who underwent 13 types of high-risk endoscopic 3Department of Health Care procedures and took preoperative warfarin or DOACs thromboembolism. Informatics, Graduate School of from 2014 to 2015. One-to-one propensity score ► The risk of endoscopy-related GI bleeding or Medicine, Tokyo Medical and matching was performed to compare postendoscopy GI thromboembolism may differ between direct Dental University, Tokyo, Japan oral anticoagulants (DOACs) and warfarin. 4Department of bleeding and thromboembolism between the warfarin Gastroenterology and and DOAC groups. ► The risk of GI bleeding or thromboembolism Hepatology, National Center Results In the propensity score-matched analysis can be affected by the use of heparin bridging for Global Health and Medicine, involving 5046 pairs, the warfarin group had a or the type of endoscopic procedure in patients Kohnodai Hospital, Chiba, Japan significantly higher proportion of GI bleeding than the taking oral anticoagulants. 5Department of Gastroenterology, Graduate DOAC group (12.0% vs 9.9%; p=0.002). No significant What are the new findings? School of Medicine, The difference was observed in thromboembolism (5.4% ► Warfarin users had a significantly higher University of Tokyo, Tokyo, Japan vs 4.7%) or in-hospital mortality (5.4% vs 4.7%). The proportion of GI bleeding after high-risk http://gut.bmj.com/ risks of GI bleeding and thromboembolism were greater endoscopic procedures than did DOAC users. Correspondence to in patients treated with warfarin plus heparin bridging ► Heparin bridging was associated with Dr Naoyoshi Nagata, or DOACs plus bridging than in patients treated with an increased risk of bleeding and Department of Gastroenterology and Hepatology, National DOACs alone. Compared with percutaneous endoscopic thromboembolism. Center for Global Health and gastrostomy, patients who underwent endoscopic ► The bleeding risk varied by the type of Medicine, 1-21-1 Toyama, submucosal dissection, endoscopic mucosal resection endoscopic procedure. Shinjuku-ku, Tokyo 162-8655, and haemostatic procedures including endoscopic How might it impact on clinical practice in the on September 24, 2021 by guest. Protected copyright. Japan; nnagata_ ncgm@ yahoo. co. jp variceal ligation or endoscopic injection sclerotherapy foreseeable future? were at the highest risk of GI bleeding among the ► Our results will be useful for decision making Received 20 February 2017 13 types of endoscopic procedures, whereas those regarding switching from warfarin to DOACs Revised 19 June 2017 who underwent lower polypectomy endoscopic before implementing high-risk endoscopic Accepted 30 July 2017 sphincterotomy or endoscopic ultrasound-guided fine procedures. needle aspiration were at moderate risk. ► Because bridging with unfractionated heparin Conclusion The risk of postendoscopy GI bleeding was does not prevent thromboembolic events higher in warfarin than DOAC users. Heparin bridging and increases the risk of bleeding events, its was associated with an increased risk of bleeding and recommendation in clinical guidelines and its did not prevent thromboembolism. The bleeding risk current clinical use should be re-evaluated. varied by the type of endoscopic procedure. ► Risk stratification by the type of endoscopic procedure may be needed in patients taking oral anticoagulants. INTRODUCTION Transient interruption of anticoagulant agents before endoscopic procedures remains controver- because of its intricate pharmacodynamic proper- To cite: Nagata N, sial because of difficulties in balancing the risks of ties and narrow therapeutic range.7 8 In contrast, Yasunaga H, Matsui H, et al. 1–6 Gut Published Online First: GI)bleeding and thromboembolism. Among anti- direct oral anticoagulants (DOACs) are prescribed [please include Day Month coagulant agents, warfarin is familiar to nearly all at a fixed dose without the need for monitoring Year]. doi:10.1136/ clinicians, and its effect can be reversed easily and or dose adjustment based on their rapid onset of gutjnl-2017-313999 rapidly.5 However, it requires complex management anticoagulant effect and short half-life,4 5 9 which Nagata N, et al. Gut 2017;0:1–8. doi:10.1136/gutjnl-2017-313999 1 Copyright Article author (or their employer) 2017. Produced by BMJ Publishing Group Ltd (& BSG) under licence. Endoscopy allow for easier management; however, specific antidotes or Outcomes and variables reversal agents for some DOACs are lacking.1 5 Some evidence The main clinical outcomes included therapeutic endoscopy-re- Gut: first published as 10.1136/gutjnl-2017-313999 on 5 September 2017. Downloaded from suggests that patients receiving DOACs have an increased risk lated GI bleeding within 30 days of endoscopy, thromboembo- of non-procedure-related GI bleeding compared with patients lism within 30 days of endoscopy and death during the hospital receiving warfarin10 11; however, the risks of procedure-related stay. GI bleeding included overt GI bleeding after the initial high- GI bleeding remain unclear. risk endoscopic procedures that required endoscopic haemo- In several previous studies, the proportion of high-risk proce- stasis and/or blood transfusion. When the initial endoscopic dure-related bleeding in patients taking anticoagulants was 38% procedure was haemostasis, postendoscopy GI bleeding was in those who underwent gastric endoscopic submucosal dissec- defined as recurrent overt GI bleeding that required endoscopic tion (ESD),1217% in those who underwent colorectal ESD,1320% haemostasis and/or blood transfusion. We defined thromboem- in those who underwent colorectal polypectomy14 and 33% in bolism as the occurrence of cardiovascular events, cerebrovas- those who underwent endoscopic ultrasound-guided fine needle cular events, pulmonary embolism, deep vein thrombosis and aspiration (EUS-FNA).15 However, these studies involved small other types of arterial thrombosis. Cardiovascular events were samples from a limited number of institutions. identified by recorded diagnoses of ischaemic heart diseases after Endoscopic guidelines recommend continuing warfarin and admission (ICD-10 codes I20–22) or performance of percuta- DOACs in patients undergoing low-risk endoscopic procedures neous coronary intervention. Cerebrovascular events were iden- and heparin bridging for warfarin users undergoing high-risk tified by recorded diagnoses of stroke after admission (ICD-10 endoscopic procedures.1–3 6 In clinical practice, DOAC users may codes I61–63) or treatment with tissue plasminogen activator. also undergo heparin bridging to prevent thromboembolism.16 Complications that occurred after admission were used to iden- However, the difference in bleeding or thromboembolic risk tify pulmonary embolism (ICD-10 code I26), deep vein throm- associated with heparin bridging between warfarin and DOAC bosis (I82) and other types of arterial thrombosis (I74). users also remains unclear. We evaluated data on age, sex, body mass index (BMI), Because only <4% of patients who undergo high-risk endo- comorbidities at admission, drugs used, heparin bridging and scopic procedures receive oral anticoagulants,17 18 no single- type of endoscopic procedures. BMI was classified into four centre study would be able to recruit a sufficient number of categories (<18.5, 18.5–24.9, 25.0–29.9 and >30.0 kg/m2) patients. In this study, therefore, we used a large national inpa- in accordance with the WHO BMI Classification.21 We evalu- tient database in Japan to (1) compare the risks of bleeding, ated 13 comorbidities at admission based on the components thromboembolism, and death between patients treated with of the Charlson Comorbidity Index: congestive heart failure, warfarin and DOACs; (2) compare these risks among 13 types peripheral vascular disease, myocardial infarction, cerebrovas- of high-risk endoscopic procedures; and (3) determine whether cular disease, dementia, chronic pulmonary disease, rheuma- heparin bridging increases the incidence of adverse events. toid disease, peptic ulcer, diabetes with and without chronic complications, hemiplegia or paraplegia, renal disease, mild- to-severe liver disease and malignancy or metastatic cancer.17–19 METHODS We assessed the use of low-dose aspirin, thienopyridines, other Design,