Real-world evidence of stroke prevention in patients with nonvalvular atrial fibrillation in the United States: the REVISIT-US study.

Background: Little data exists regarding the effectiveness and safety of rivaroxaban or apixaban versus warfarin in nonvalvular atrial fibrillation (NVAF) patients treated outside of clinical trials.

Methods: This was a retrospective study using MarketScan claims from January 2012 to October 2014. We included adults, newly initiated on rivaroxaban, apixaban or warfarin, with a baseline CHADS-VASc score ≥2, ≥2 diagnosis codes for NVAF and ≥180 days of continuous medical and prescription benefits. Patients with a prior stroke, systemic embolism or intracranial hemorrhage (ICH) were excluded. Eligible rivaroxaban or apixaban users were 1:1 propensity-score matched individually to warfarin users. Cox regression was performed to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for rivaroxaban and apixaban versus warfarin for the combined endpoint of ischemic stroke or ICH and each endpoint individually.

Results: Upon matching 11,411 rivaroxaban to 11,411 warfarin users, rivaroxaban was associated with a significant reduction of the combined endpoint of ischemic stroke or ICH versus warfarin (HR = 0.61, 95% CI = 0.45-0.82). ICH was significantly (HR = 0.53, 95% CI = 0.35-0.79) and ischemic stroke nonsignificantly reduced (HR = 0.71, 95% CI = 0.47-1.07) by rivaroxaban versus warfarin. After matching 4083 apixaban and 4083 warfarin users, apixaban was found to nonsignificantly reduce the combined endpoint of ischemic stroke or ICH versus warfarin (HR = 0.63, 95% CI = 0.35-1.12) and to reduce ICH risk (HR = 0.38, 95% CI = 0.17-0.88). Ischemic stroke risk was nonsignificantly increased with apixaban (HR = 1.13, 95% CI = 0.49-2.63) versus warfarin.

Limitations: Sample size and number of combined events observed were relatively small. Residual confounding could not be ruled out.

Conclusions: Rivaroxaban and apixaban were associated with less ICH than warfarin and both are likely associated with reductions in the combined endpoint. Further investigation to validate the numerically higher rate of ischemic stroke with apixaban versus warfarin is required.