Major bleeding in users of direct oral anticoagulants in atrial fibrillation: A pooled analysis of results from multiple population-based cohort studies

被引：21

作者：

van den Ham, Hendrika A. ^{[1
]}

Souverein, Patrick C. ^{[1
]}

Klungel, Olaf H. ^{[1
]}

Platt, Robert W. ^{[2
]}

Ernst, Pierre ^{[2
]}

Dell'Aniello, Sophie ^{[2
]}

Schmiedl, Sven ^{[3
,4
]}

Grave, Birgit ^{[5
]}

Rottenkolber, Marietta ^{[6
]}

Huerta, Consuelo ^{[7
]}

Martin Merino, Elisa ^{[7
]}

Leon-Munoz, Luz M. ^{[7
]}

Montero, Dolores ^{[7
]}

Andersen, Morten ^{[8
]}

Aakjaer, Mia ^{[8
]}

De Bruin, Marie L. ^{[1
,9
]}

Gardarsdottir, Helga ^{[1
,10
,11
]}

机构：

[1] Univ Utrecht, Utrecht Inst Pharmaceut Sci, Div Pharmacoepidemiol & Clin Pharmacol, Utrecht, Netherlands

[2] Jewish Gen Hosp, Canada & Canadian Network Observat Drug Effect St, Lady Davis Inst, Montreal, PQ, Canada

[3] Witten Herdecke Univ UW H, Fac Hlth, Sch Med, Dept Clin Pharmacol, Witten, Germany

[4] Helios Univ Hosp Wuppertal, Philipp Klee Inst Clin Pharmacol, Wuppertal, Germany

[5] AOK NORDWEST, Dortmund, Germany

[6] Klinikum Univ Munchen, Med Klin & Poliklin 4, Diabet Res Grp, Munich, Germany

[7] Spanish Agcy Med & Med Devices AEMPS, Div Pharmacoepidemiol & Pharmacovigilance, Madrid, Spain

[8] Univ Copenhagen, Fac Hlth & Med Sci, Dept Drug Design & Pharmacol, Pharmacovigilance Res Grp, Copenhagen, Denmark

[9] Univ Copenhagen, Fac Hlth & Med Sci, Copenhagen Ctr Regulatory Sci, Dept Pharm, Copenhagen, Denmark

[10] Univ Med Ctr Utrecht, Dept Clin Pharm, Div Lab & Pharm, Utrecht, Netherlands

[11] Univ Iceland, Fac Pharmaceut Sci, Reykjavik, Iceland

来源：

PHARMACOEPIDEMIOLOGY AND DRUG SAFETY | 2021年 / 30卷 / 10期

基金：

加拿大健康研究院;

关键词：

atrial fibrillation; cohort studies; directoral anticoagulants; major bleeding; oral anticoagulants; vitamin K antagonists; MORTALITY RISKS; WARFARIN; DABIGATRAN; RIVAROXABAN; APIXABAN; SAFETY; MANAGEMENT; STROKE; GUIDELINES; EFFICACY;

D O I：

10.1002/pds.5317

中图分类号：

R1 [预防医学、卫生学];

学科分类号：

1004 ; 120402 ;

摘要：

Objective To establish the risk of major bleeding in direct oral anticoagulant (DOAC) users (overall and by class) versus vitamin K antagonist (VKA) users, using health care databases from four European countries and six provinces in Canada. Methods A retrospective cohort study was performed according to a similar protocol. First-users of VKAs or DOACs with a diagnosis of non-valvular atrial fibrillation (NVAF) were included. The main outcome of interest was major bleeding and secondary outcomes included gastrointestinal (GI) bleeding and intracranial haemorrhage (ICH). Incidence rates of events per 1000 person years were calculated. Hazard ratios (HRs) and 95% confidence intervals (95% CI) were estimated using a Cox proportional hazard regression model. Exposure and confounders were measured and analysed in a time-dependant way. Risk estimates were pooled using a random effect model. Results 421 523 patients were included. The risk of major bleeding for the group of DOACs compared to VKAs showed a pooled HR of 0.94 (95% CI: 0.87-1.02). Rivaroxaban showed a modestly increased risk (HR 1.11, 95% CI: 1.06-1.16). Apixaban and dabigatran showed a decreased risk of respectively HR 0.76 (95% CI: 0.69-0.84) and HR 0.85 (95% CI: 0.75-0.96). Conclusions This study confirms that the risk of major bleeding of DOACs compared to VKAs is not increased when combining all DOACs. However, we observed a modest higher risk of major bleeding for rivaroxaban, whereas for apixaban and dabigatran lower risks of major bleeding were observed compared to VKAs.

引用

页码：1339 / 1352

页数：14