Elderly Bleeding Risk of Direct Oral Anticoagulants in Nonvalvular Atrial Fibrillation: A Systematic Review and Meta-Analysis of Cohort Studies

INTRODUCTION: The 2014 American Heart Association (AHA)/American College of Cardiology (ACC)/Heart Rhythm Society (HRS) guidelines recommend anticoagulation to reduce clot formation and the risk of thromboembolic events in patients with atrial fibrillation but does not specify guidelines for the elderly population. Direct oral anticoagulants (DOACs) are newer US FDA-approved alternatives to warfarin and include dabigatran, rivaroxaban, apixaban and edoxaban. The efficacy of DOACs is heavily researched, but few studies have evaluated their bleeding risk. OBJECTIVES: This systematic review and meta-analysis investigates which DOAC has the lowest bleeding risk in elderly patients with nonvalvular atrial fibrillation (NVAF). METHODS: CINAHL and MEDLINE databases were searched using specific keywords, and 244 results were identified and screened. Inclusion criteria required a major bleeding event requiring hospitalization as an outcome and excluded patients with severe renal failure. Articles that met inclusion criteria were assessed for risk of bias using the Cochrane Tool to Assess Risk of Bias in Cohort Studies. Review Manager (version 5) was used to perform the random-effects model meta-analysis. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated. P < 0.05 was considered statistically significant. RESULTS: Six articles met inclusion criteria and encompassed 446,042 patients in total. Apixaban and dabigatran had statistically significant risk reductions compared with warfarin, whereas rivaroxaban did not (HR 0.60 [95% CI 0.52–0.69], p < 0.00001; HR 0.79 [95% CI 0.70–0.90], p = 0.0005; HR 1.03 [95% CI 0.86–1.22], p = 0.77, respectively.) Data regarding edoxaban were limited and thus not included in the analysis. CONCLUSION: Apixaban and dabigatran have a significantly decreased major bleeding risk (40 and 21%, respectively) compared with warfarin. There was no statistical difference in bleeding risk between rivaroxaban and warfarin. Head-to-head prospective randomized controlled trials are required to assess the true bleeding risk of each DOAC.