Clinical outcomes with rivaroxaban in patients transitioned from vitamin K antagonist therapy: a subgroup analysis of a randomized trial.
BACKGROUND: In ROCKET AF (Rivaroxaban Once-Daily, Oral, Direct Factor Xa Inhibition Compared With Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation), a large randomized, clinical trial, rivaroxaban was noninferior to warfarin in preventing stroke or systemic embolism in patients with atrial fibrillation. OBJECTIVE: To determine the efficacy and safety of rivaroxaban compared with warfarin among vitamin K antagonist (VKA)-naive and VKA-experienced patients. DESIGN: Prespecified subgroup analysis. (ClinicalTrials.gov: NCT00403767). SETTING: Global. PATIENTS: 14,264 persons with atrial fibrillation. MEASUREMENTS: Interaction of the relative treatment effect of rivaroxaban and warfarin on stroke or systemic embolism among VKA-naive and VKA-experienced patients. RESULTS: Overall, 7897 (55.4%) patients were VKA-experienced and 6367 (44.6%) were VKA-naive. The effect of rivaroxaban versus warfarin on stroke or systemic embolism was consistent: Rates per 100 patient-years of follow-up were 2.32 versus 2.87 for VKA-naive patients (hazard ratio [HR], 0.81 [95% CI, 0.64 to 1.03]) and 1.98 versus 2.09 for VKA-experienced patients (HR, 0.94 [CI, 0.75 to 1.18]; interaction P = 0.36). During the first 7 days, rivaroxaban was associated with more bleeding than warfarin (HR in VKA-naive patients, 5.83 [CI, 3.25 to 10.44], and in VKA-experienced patients, 6.66 [CI, 3.83 to 11.58]; interaction P = 0.53). After 30 days, rivaroxaban was associated with less bleeding than warfarin in VKA-naive patients (HR, 0.84 [CI, 0.74 to 0.95]) and similar bleeding in VKA-experienced patients (HR, 1.06 [CI, 0.96 to 1.17]; interaction P = 0.003). LIMITATION: The trial was not designed to detect differences in these subgroups. CONCLUSION: The efficacy of rivaroxaban in VKA-experienced and VKA-naive patients was similar to that of the overall trial. There were more bleeding events within 7 days of study drug initiation with rivaroxaban, but after 30 days, rivaroxaban was associated with less bleeding in VKA-naive patients and similar bleeding in VKA-experienced patients. This information may be useful to clinicians considering a transition to rivaroxaban for patients receiving VKA therapy. PRIMARY FUNDING SOURCE: Johnson & Johnson and Bayer HealthCare.
Mahaffey, KW; Wojdyla, D; Hankey, GJ; White, HD; Nessel, CC; Piccini, JP; Patel, MR; Berkowitz, SD; Becker, RC; Halperin, JL; Singer, DE; Califf, RM; Fox, KAA; Breithardt, G; Hacke, W
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