Effectiveness and Safety of Oral Anticoagulants Among Nonvalvular Atrial Fibrillation Patients

Abstract

Background and Purpose- This ARISTOPHANES study (Anticoagulants for Reduction in Stroke: Observational Pooled Analysis on Health Outcomes and Experience of Patients) used multiple data sources to compare stroke/systemic embolism (SE) and major bleeding (MB) among a large number of nonvalvular atrial fibrillation patients on non-vitamin K antagonist oral anticoagulants (NOACs) or warfarin. Methods- A retrospective observational study of nonvalvular atrial fibrillation patients initiating apixaban, dabigatran, rivaroxaban, or warfarin from January 1, 2013, to September 30, 2015, was conducted pooling Centers for Medicare and Medicaid Services Medicare data and 4 US commercial claims databases. After 1:1 NOAC-warfarin and NOAC-NOAC propensity score matching in each database, the resulting patient records were pooled. Cox models were used to evaluate the risk of stroke/SE and MB across matched cohorts. Results- A total of 285 292 patients were included in the 6 matched cohorts: 57 929 apixaban-warfarin, 26 838 dabigatran-warfarin, 83 007 rivaroxaban-warfarin, 27 096 apixaban-dabigatran, 62 619 apixaban-rivaroxaban, and 27 538 dabigatran-rivaroxaban patient pairs. Apixaban (hazard ratio [HR], 0.61; 95% CI, 0.54-0.69), dabigatran (HR, 0.80; 95% CI, 0.68-0.94), and rivaroxaban (HR, 0.75; 95% CI, 0.69-0.82) were associated with lower rates of stroke/SE compared with warfarin. Apixaban (HR, 0.58; 95% CI, 0.54-0.62) and dabigatran (HR, 0.73; 95% CI, 0.66-0.81) had lower rates of MB, and rivaroxaban (HR, 1.07; 95% CI, 1.02-1.13) had a higher rate of MB compared with warfarin. Differences exist in rates of stroke/SE and MB across NOACs. Conclusions- In this largest observational study to date on NOACs and warfarin, the NOACs had lower rates of stroke/SE and variable comparative rates of MB versus warfarin. The findings from this study may help inform the discussion on benefit and risk in the shared decision-making process for stroke prevention between healthcare providers and nonvalvular atrial fibrillation patients. Clinical Trial Registration- URL: https://www.clinicaltrials.gov/ . Unique identifier: NCT03087487.

Keywords: anticoagulants; apixaban; dabigatran; hemorrhage; rivaroxaban; stroke; warfarin.

Figures

Figure 1.

Kaplan-Meier curves for stroke/SE and major bleeding. A, Cumulative incidence of stroke/systemic embolism (SE) and major bleeding in non–vitamin K antagonist oral anticoagulant (NOAC)-warfarin propensity score–matched cohorts. B, Cumulative incidence of Stroke/SE and major bleeding in NOAC-NOAC propensity score–matched cohorts.

Figure 2.

Comparison of stroke/SE and major bleeding between OACs. A, Incidence rates and hazard ratios of stroke/systemic embolism (SE) and major bleeding for non–vitamin K antagonist oral anticoagulants (NOACs) vs warfarin propensity score–matched cohorts. B, Incidence rates and hazard ratios of stroke/SE and major bleeding for NOACs vs NOACs propensity score–matched cohorts. GI indicates gastrointestinal; and ICH, intracranial hemorrhage.

Figure 3.

Subgroup analysis. A, Propensity score–matched hazard ratios of stroke/systemic embolism (SE) for non–vitamin K antagonist oral anticoagulant (NOAC)-warfarin comparisons. †Age was included in the model because it was not balanced after propensity score matching (PSM) for apixaban and warfarin patients with prior stroke and for dabigatran and warfarin patients with renal disease. ‡Charlson Comorbidity Index (CCI) and anemia and coagulation defects were included in the model because they were not balanced after PSM between 75 mg dabigatran and warfarin patients. B, Propensity score–matched hazard ratios of major bleeding for NOAC-warfarin comparisons. †Age was included in the model because it was not balanced after PSM for apixaban and warfarin patients with prior stroke and for dabigatran and warfarin patients with renal disease. ‡CCI and anemia and coagulation defects were included in the model because they were not balanced after PSM between 75 mg dabigatran and warfarin patients. C, Propensity score–matched hazard ratios of stroke/SE for NOAC-NOAC comparisons. D, Propensity score–matched hazard ratios of major bleeding for NOAC-NOAC comparisons. *Significant interactions were found (whether treatment effect was statistically different across subgroups). CAD indicates coronary artery disease; CHF, congestive heart failure; HAS-BLED, hypertension, abnormal renal and liver function, stroke, bleeding, labile international normalized ratio, elderly, drugs and alcohol; and PAD, peripheral artery disease.