Clinical Outcomes of Switching From Warfarin to Apixaban or Rivaroxaban in Patients With Atrial Fibrillation: A Nationwide Multidatabase Study

Abstract

Background: The benefits of switching from warfarin to direct oral anticoagulants in atrial fibrillation remain unclear.

Methods: This retrospective study used the Medicare fee-for-service (2013-2020) and Optum Deidentified Clinformatics Data Mart databases (2013-2023). Among patients with atrial fibrillation who received warfarin for at least 180 days, we created 2 cohorts: (1) patients switching to apixaban versus continuing warfarin (the apixaban cohort) and (2) patients switching to rivaroxaban versus continuing warfarin (the rivaroxaban cohort). The index date was the switch date for switchers and a matched date based on warfarin duration for warfarin continuers. After 1:1 propensity score matching, we estimated the rate ratios (RR) for a composite of ischemic stroke, major bleeding, and death in each database and pooled the results using meta-analysis. Subgroup analyses by claims-based frailty and by follow-up time (first 60 days versus beyond 60 days) were performed.

Results: In the apixaban cohort (n=164 480; mean age, 80.5 years; 55.5% female; median follow-up, 354 days), switching to apixaban was associated with a lower rate of composite outcome (97.1 versus 104.9 per 1000 person-years; rate ratio, 0.92 [95% CI, 0.89-0.95]) compared with continuing warfarin. In the rivaroxaban cohort (n=96 030, mean age 79.7 years, 54.8% female, median follow-up 365 days), switching to rivaroxaban was associated with an increased rate of composite outcome (105.8 versus 99.3 per 1000 person-years; rate ratio, 1.08 [95% CI, 1.04-1.13]). No heterogeneity by frailty levels was observed. However, switching was associated with an initial risk increase within the first 60 days, followed by risk attenuation beyond 60 days, for both apixaban and rivaroxaban.

Conclusions: In patients with atrial fibrillation on warfarin therapy, switching to apixaban may reduce the risk of ischemic stroke, major bleeding, and death, whereas switching to rivaroxaban may increase the risk. For both apixaban and rivaroxaban, switching may temporarily increase risk during the first 60 days.

Keywords: anticoagulants; apixaban; atrial fibrillation; ischemic stroke; rivaroxaban.

Figure 1.

Propensity Score Matched Analysis of Clinical Outcomes in Patients with Atrial Fibrillation Switching to Apixaban versus Continuing Warfarin Abbreviations: CI, confidence interval; GI, gastrointestinal; RR, rate ratio; py, person-years; RD, rate difference.

Figure 2.

Propensity Score Matched Analysis of Early versus Late Clinical Outcomes in Patients with Atrial Fibrillation Switching to Apixaban versus Continuing Warfarin Abbreviations: CI, confidence interval; GI, gastrointestinal; RR, rate ratio; py, person-years; RD, rate difference. The p-value by period tests whether the association (RR or RD) between switching to apixaban and continuing warfarin differs between frail and non-frail individuals.

Figure 3.

Propensity Score Matched Analysis of Clinical Outcomes in Patients with Atrial Fibrillation Switching to Rivaroxaban versus Continuing Warfarin Abbreviations: CI, confidence interval; GI, gastrointestinal; RR, rate ratio; py, person-years; RD, rate difference.

Figure 4.

Propensity Score Matched Analysis of Early versus Late Clinical Outcomes in Patients with Atrial Fibrillation Switching to Rivaroxaban versus Continuing Warfarin Abbreviations: CI, confidence interval; GI, gastrointestinal; RR, rate ratio; py, person-years; RD, rate difference. The p-value by period tests whether the association (RR or RD) between switching to rivaroxaban and continuing warfarin differs between frail and non-frail individuals.