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

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.

Non‐synonymous alterations in AKR7A3 and ABCA6 correlate with bleeding in aged patients treated with rivaroxaban

“…3 , 4 NVAF patients treated with rivaroxaban had a higher risk of gastrointestinal bleeding in the first 90 days. 5 The incidence rates of major bleeding and intracranial hemorrhage induced by rivaroxaban were reported to reach 3.6% and 0.5%, respectively, in patients with NVAF. 6 The expected range of plasma levels for standard dose of rivaroxaban were 12–137 ng/ml at peak and 178–343 ng/ml at trough, respectively, reported in clinical pharmacokinetic studies.…”

“…Potential risks for bleeding include abnormal coagulation phase (prolonged PT or elevated INR), subcutaneous or mucosal bleeding, hematuria, gastrointestinal bleeding, and intracranial hemorrhage, which has been associated with the risk of hospitalization and death 3,4 . NVAF patients treated with rivaroxaban had a higher risk of gastrointestinal bleeding in the first 90 days 5 . The incidence rates of major bleeding and intracranial hemorrhage induced by rivaroxaban were reported to reach 3.6% and 0.5%, respectively, in patients with NVAF 6 .…”

Upper airway hematoma: An unusual presentation of acute upper airway obstruction

“…Even though this is a rare complication, treating clinicians should maintain a high index of suspicion and evaluate and treat promptly to prevent a fatal outcome. Switching them to DOACs may be a reasonable option for high-risk patients who continue to require systemic anticoagulation [ 11 ].…”

Advances in the Management of Atrial Fibrillation with a Special Focus on Non-Pharmacological Approaches to Prevent Thromboembolism: A Review of Current Recommendations

“…However, in practice the risk of bleeding may differ from those observed in randomized trials. In most contemporary studies, this risk is about71 0.2%–0.4% per year. While this risk is not trivial, it is substantially lower than the risk of ischemic stroke in the vast majority of patients with AF with CHA 2 DS 2 -VASc ≥2 who are not anticoagulated 72…”