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

Abstract

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 CHA₂DS₂-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.

Keywords:

• Anticoagulants
• Apixaban
• Nonvalvular atrial fibrillation
• Rivaroxaban
• Stroke prevention
• Warfarin

Transparency

Declaration of funding

The REVISIT-US study was supported by Bayer Pharma AG.

Declaration of financial/other relationships

C.I.C. has disclosed that he has received grant funding and consultancy fees from Janssen Pharmaceuticals, Bayer and Boehringer Ingelheim Pharmaceuticals. M.A. has disclosed that he has received consulting fees and speaker honoraria from Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Daichii Sankyo and Pfizer. E.P.S. has disclosed that he has no significant relationships with or financial interests in any commercial companies related to this study or article. T.E. and K.B. have disclosed that they are employees of Bayer Pharma AG. H.B. has disclosed that he has received honoraria for lectures from Advanced Circulatory Systems, Bayer, Biotronik, Boehringer Ingelheim, Boston Scientific, Bristol-Myers Squibb, Cardiome, Daiichi Sankyo, Impulse-Dynamics, Jolife, NayaMed, Medtronic, Lilly, MSD, Physiocontrol, Pfizer, Sanofi, Servier, Sorin and St. Jude Medical; honoraria for advisory board activities from Bayer, Boehringer Ingelheim, Biotronik, Biosense-Webster, Bristol-Myers Squibb, Boston Scientific, Daiichi Sankyo, Medtronic, MSD, NayaMed, Physiocontrol, Pfizer and Sanofi; been involved with clinical trials for Biotronik, CVRx, Daiichi Sankyo, Impulse Dynamics, NayaMed, Novartis, Medtronic, MSD, Respicardia, Resmed, Sorin, St. Jude Medical and Sanofi. R.C. has disclosed that he has acted as a consultant to Abbott, Bayer, Biosense Webster, Boehringer Ingelheim, Boston Scientific, Daiichi Sankyo, ELA Sorin, Medtronic, Pfizer and St. Jude; participated in speakers’ bureaus for Abbot, BARD, Bayer, Biosense Webster, Boehringer Ingelheim, Boston Scientific, Medtronic, Sanofi and St. Jude; acted as a study investigator for Abbott, BARD, Bayer, Biosense Webster, Cameron Health, Medtronic, Pfizer and Sanofi; received grants from BARD, Biosense Webster, Boston Scientific, ELA Sorin, Medtronic, St. Jude; and holds equity and intellectual property rights in Cameron Health.

CMRO peer reviewers on this manuscript have received an honorarium from CMRO for their review work, but have no other relevant financial relationships to disclose.

Notice of correction

Please note that the abstract has been corrected since the article was first published online (20 September 2016)