Advertisement

Bleeding risk comparison between direct oral anticoagulants at doses approved for atrial fibrillation and aspirin: systematic review, meta-analysis and meta-regression

      Highlights

      • Guidelines do not recommend aspirin for stroke prevention in atrial fibrillation
      • However, many patients are still treated with aspirin due to presumed safety profile
      • We found no difference in safety between direct oral anticoagulants and aspirin
      • The level of evidence of the related recommendations should be upgraded

      Abstract

      Background

      A considerable proportion of patients with atrial fibrillation (AF) are still treated with aspirin despite current guidelines due to presumed favorable safety.

      Aim

      We performed a systematic review and meta-analysis of bleeding outcomes in randomized controlled trials (RCTs) comparing direct oral anticoagulants (DOACs) at doses approved for AF vs. aspirin.

      Methods

      We searched PubMed and Scopus for phase-III RCTs of DOACs at AF-approved doses vs. aspirin. Outcomes assessed were major-, intracranial-, gastrointestinal-, clinically-relevant-non-major- and fatal bleeding. We performed two subgroup analyses: one per patient population i.e. those at high risk of arterial or venous thromboembolism, and one per DOAC. We also performed a meta-regression to assess the association with patient age.

      Results

      In 4 eligible trials (20,440 patients) comparing DOACs vs. aspirin, the ORs were: 1.52 (95%CI: 0.91–2.53) for major bleeding in patients at high risk of arterial thromboembolism and 1.55 (95%CI:0.99-2.45, relative-risk-increase:55%, absolute-risk-increase:0.6%, number-needed-to-harm:170) in the overall analysis; 1.39 (95%CI:0.62–3.14) for intracranial bleeding in patients at high risk of arterial thromboembolism which was similar for the overall analysis; 1.27 (95%CI: 0.84–1.92) for gastrointestinal bleeding in patients at high risk of arterial thromboembolism and 1.26 (95%CI:0.86-1.85) in the overall analysis. Patient age was not a predictor of the magnitude of ORs for all bleeding outcomes.

      Conclusion

      The present meta-analysis does not support the use of aspirin over DOACs in AF. Accordingly, the level of evidence of the related recommendations should be upgraded, which in turn may reduce further the proportion of AF patients treated with antiplatelets.

      Keywords

      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to European Journal of Internal Medicine
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • January CT
        • Wann LS
        • Alpert JS
        • Calkins H
        • Cigarroa JE
        • Cleveland JC
        • et al.
        AHA/ACC/HRS guideline for the management of patients with atrial fibrillation: a report of the American College of cardiology/American heart association task force on practice guidelines and the heart rhythm society.
        Circulation. 2014. 2014; 130: e199-e267
        • Lip GY.
        The role of aspirin for stroke prevention in atrial fibrillation.
        Nat Rev Cardiol. 2011; 8: 602-606
        • Stroke Prevention in Atrial Fibrillation Study
        Final results.
        Circulation. 1991; 84: 527-539
        • Kirchhof P
        • Benussi S
        • Kotecha D
        • Ahlsson A
        • Atar D
        • Casadei B
        • et al.
        ESC Guidelines for the management of atrial fibrillation developed in collaboration with EACTS.
        Eur Heart J 2016. 2016; 37: 2893-2962
        • January CT
        • Wann LS
        • Calkins H
        • Chen LY
        • Cigarroa JE
        • Cleveland JC
        • et al.
        AHA/ACC/HRS focused update of the 2014 AHA/ACC/HRS guideline for the management of patients with atrial fibrillation.
        Circulation. 2019; (0:CIR.0000000000000665)
        • Lip GYH
        • Banerjee A
        • Boriani G
        • Chiang Ce
        • Fargo R
        • Freedman B
        • et al.
        Antithrombotic therapy for atrial fibrillation: chest guideline and expert panel report.
        Chest. 2018; 154: 1121-1201
        • Sur NB
        • Wang K
        • Di Tullio MR
        • Gutierrez CM
        • Dong C
        • Koch S
        • et al.
        Disparities and temporal trends in the use of anticoagulation in patients with ischemic stroke and atrial fibrillation.
        Stroke. 2019; 50: 1452-1459
        • McIntyre WF
        • Conen D
        • Olshansky B
        • Halperin JL
        • Hayek E
        • Huisman MV
        • et al.
        Stroke-prevention strategies in North American patients with atrial fibrillation: The GLORIA-AF registry program.
        Clin Cardiol. 2018; 41: 744-751
        • Huisman MV
        • Rothman KJ
        • Paquette M
        • Teutsch C
        • Diener HC
        • Dubner SJ
        • et al.
        The changing landscape for stroke prevention in AF: findings from the GLORIA-AF registry phase 2.
        J Am Coll Cardiol. 2017; 69: 777-785
        • Huisman MV
        • Ma CS
        • Diener HC
        • Dubner SJ
        • Halperin JL
        • Rothman KJ
        • et al.
        Antithrombotic therapy use in patients with atrial fibrillation before the era of non-vitamin K antagonist oral anticoagulants: the global registry on long-term oral antithrombotic treatment in patients with atrial fibrillation (GLORIA-AF) Phase I cohort.
        Europace. 2016; 18: 1308-1318
        • Huisman MV
        • Rothman KJ
        • Paquette M
        • Teutsch C
        • Diener HC
        • Dubner SJ
        • et al.
        Antithrombotic treatment patterns in patients with newly diagnosed nonvalvular atrial fibrillation: the GLORIA-AF registry, Phase II.
        Am J Med. 2015; 128 (1306-13 e1)
        • Ntaios G
        • Sagris D
        • Gioulekas F
        • Galanis P
        • Pardali C
        • Vemmou A
        • et al.
        20-year trends of characteristics and outcomes of stroke patients with atrial fibrillation.
        Int J Stroke. 2018; 13: 707-716
        • Dorsch M
        • Pokorney S
        • Birmingham M
        • House JA
        • Moore K
        • James B
        • et al.
        Oral anticoagulation underused and aspirin overused for atrial fibrillation with advanced chronic kidney disease status.
        J Am Coll Cardiol. 2019; 73: 408
        • Apenteng PN
        • Gao H
        • Hobbs FR
        • Fitzmaurice DA
        Temporal trends in antithrombotic treatment of real-world UK patients with newly diagnosed atrial fibrillation: findings from the GARFIELD-AF registry.
        BMJ Open. 2018; 8e018905
        • Verheugt FWA
        • Gao H
        • Al Mahmeed W
        • Ambrosio G
        • Angchaisuksiri P
        • Atar D
        • et al.
        Characteristics of patients with atrial fibrillation prescribed antiplatelet monotherapy compared with those on anticoagulants: insights from the GARFIELD-AF registry.
        Eur Heart J. 2017; 39: 464-473
        • Huisman MV
        • Rothman KJ
        • Paquette M
        • Teutsch C
        • Diener HC
        • Dubner SJ
        • et al.
        The changing landscape for stroke prevention in AF: findings from the GLORIA-AF registry Phase 2.
        J Am Coll Cardiol. 2017; 69: 777-785
        • Palareti G
        • Salomone L
        • Cavazza M
        • Guidi M
        • Muscari A
        • Boriani G
        • et al.
        Stroke/thromboembolism and intracranial hemorrhage in a real-world atrial fibrillation population: the complications of atrial fibrillation in the Bologna Area (CAFBO) study.
        Chest. 2014; 146: 1073-1080
        • Camm AJ
        • Accetta G
        • Ambrosio G
        • Atar D
        • Bassand J-P
        • Berge E
        • et al.
        Evolving antithrombotic treatment patterns for patients with newly diagnosed atrial fibrillation.
        Heart. 2017; 103: 307-314
        • Connolly SJ
        • Eikelboom J
        • Joyner C
        • Diener H-C
        • Hart R
        • Golitsyn S
        • et al.
        Apixaban in Patients with Atrial Fibrillation.
        N Engl J Med. 2011; 364: 806-817
        • Weitz JI
        • Lensing AWA
        • Prins MH
        • Bauersachs R
        • Beyer-Westendorf J
        • Bounameaux H
        • et al.
        Rivaroxaban or aspirin for extended treatment of venous thromboembolism.
        N Engl J Med. 2017; 376: 1211-1222
        • Hart RG
        • Sharma M
        • Mundl H
        • Kasner SE
        • Bangdiwala SI
        • Berkowitz SD
        • et al.
        Rivaroxaban for stroke prevention after embolic stroke of undetermined source.
        N Engl J Med. 2018; 378: 2191-2201
        • Diener HC
        • Sacco RL
        • Easton JD
        • Granger CB
        • Bernstein RA
        • Uchiyama S
        • et al.
        Dabigatran for prevention of stroke after embolic stroke of undetermined source.
        N Engl J Med. 2019; 380: 1906-1917
        • Liberati A
        • Altman DG
        • Tetzlaff J
        • Mulrow C
        • Gøtzsche PC
        • Ioannidis JPA
        • et al.
        The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate healthcare interventions: explanation and elaboration.
        BMJ. 2009; 339: b2700
        • Chao TF
        • Liu CJ
        • Lin YJ
        • Chang SL
        • Lo LW
        • Hu YF
        • et al.
        Oral anticoagulation in very elderly patients with atrial fibrillation: a nationwide cohort study.
        Circulation. 2018; 138: 37-47
        • Deitelzweig S
        • Keshishian A
        • Li X
        • Kang A
        • Dhamane AD
        • Luo X
        • et al.
        Comparisons between oral anticoagulants among older nonvalvular atrial fibrillation patients.
        J Am Geriatr Soc. 2019;
        • Sardar P
        • Chatterjee S
        • Chaudhari S
        • Lip GY
        New oral anticoagulants in elderly adults: evidence from a meta-analysis of randomized trials.
        J Am Geriatr Soc. 2014; 62: 857-864