Bleeding Risk in Nonvalvular Atrial Fibrillation Patients Receiving Direct Oral Anticoagulants and Warfarin: A Systematic Review and Meta-Analysis of Observational Studies.

Alla Iansavitchene,Rohan Kehar,Yimin Pearl Wang,Alejandro Lazo-Langner

doi:10.1055/s-0040-1714918

Abstract

Introduction In randomized trials in atrial fibrillation (AF) patients on direct oral anticoagulants (DOACs) have a lower risk of bleeding compared with warfarin. However, data from randomized trials may not extrapolate to general population. We aimed to determine the risk of bleeding in patients on DOACs in observational studies. Materials and Methods Observational studies from 1990 to January 2019 were included. A pooled effect hazard ratio (HR) was calculated with a random effects model using the generic inverse variance method. Subgroup analyses according to previous anticoagulants exposure, study type, funding source, and DOAC type (direct thrombin inhibitors vs. factor Xa inhibitors) were conducted. Results A total of 35 studies comprising 2,356,201 patients were included. The average pooled HR for observational data was 0.78 (95% confidence interval [CI] 0.71, 0.85). There were no statistically significant differences in pooled HR by previous exposure to anticoagulants, DOAC type (direct thrombin vs. factor Xa inhibitors), study type, and funding source. Among patients receiving factor Xa inhibitors, patients on apixaban had a lower risk of bleeding compared with warfarin (HR 0.60, 95% CI 0.50, 0.71, p < 0.001) in contrast to those on rivaroxaban (HR 0.98, 95% CI 0.91, 1.06, p = 0.60). Conclusion In observational studies, AF patients on DOACs experience less bleeding events compared with warfarin; however, apixaban and dabigatran, but not rivaroxaban, have a lower risk of bleeding than warfarin.

Highlights

In randomized trials in atrial fibrillation (AF) patients on direct oral anticoagulants (DOACs) have a lower risk of bleeding compared with warfarin
Among patients receiving factor Xa inhibitors, patients on apixaban had a lower risk of bleeding compared with warfarin (HR 0.60, 95% CI 0.50, 0.71, p < 0.001) in contrast to those on rivaroxaban (HR 0.98, 95% CI 0.91, 1.06, p 1⁄4 0.60)
Direct oral anticoagulants (DOACs)—including direct thrombin inhibitors (DTI) and direct factor Xa (FXa) inhibitors—have become an alternative to warfarin due to its relatively stable pharmacokinetics[5] resulting in no need for laboratory monitoring and less pharmacological interactions compared with warfarin.[6]

Summary

Introduction

In randomized trials in atrial fibrillation (AF) patients on direct oral anticoagulants (DOACs) have a lower risk of bleeding compared with warfarin. There were no statistically significant differences in pooled HR by previous exposure to anticoagulants, DOAC type (direct thrombin vs factor Xa inhibitors), study type, and funding source. Conclusion In observational studies, AF patients on DOACs experience less bleeding events compared with warfarin; apixaban and dabigatran, but not rivaroxaban, have a lower risk of bleeding than warfarin. There are valvular abnormalities such as the presence of mitral stenosis or artificial valves.[4] The standard oral anticoagulant therapy administered to nonvalvular AF patient has typically been vitamin K antagonists, warfarin.[1] In recent years, direct oral anticoagulants (DOACs)—including direct thrombin inhibitors (DTI) and direct factor Xa (FXa) inhibitors—have become an alternative to warfarin due to its relatively stable pharmacokinetics[5] resulting in no need for laboratory monitoring and less pharmacological interactions compared with warfarin.[6]

Objectives

Methods

Results

Conclusion