Rivaroxaban compared with warfarin in patients with atrial fibrillation and previous stroke or transient ischaemic attack: a subgroup analysis of ROCKET AF.

SummaryBackground In ROCKET AF, rivaroxaban was non-inferior to adjusted-dose warfarin in preventing stroke or systemicembolism among patients with atrial fi brillation (AF). We aimed to investigate whether the effi cacy and safety ofrivaroxaban compared with warfarin is consistent among the subgroups of patients with and without previous strokeor transient ischaemic attack (TIA).Methods In ROCKET AF, patients with AF who were at increased risk of stroke were randomly assigned (1:1) in adouble-blind manner to rivaroxaban 20 mg daily or adjusted dose warfarin (international normalised ratio 2·0–3·0).Patients and investigators were masked to treatment allocation. Between Dec 18, 2006, and June 17, 2009, 14 264 patientsfrom 1178 centres in 45 countries were randomly assigned. The primary endpoint was the composite of stroke or non-CNS systemic embolism. In this substudy we assessed the interaction of the treatment eff ects of rivaroxaban andwarfarin among patients with and without previous stroke or TIA. Effi cacy analyses were by intention to treat andsafety analyses were done in the on-treatment population. ROCKET AF is registered with ClinicalTrials.gov, numberNCT00403767.Findings 7468 (52%) patients had a previous stroke (n=4907) or TIA (n=2561) and 6796 (48%) had no previous strokeor TIA. The number of events per 100 person-years for the primary endpoint in patients treated with rivaroxabancompared with warfarin was consistent among patients with previous stroke or TIA (2·79% rivaroxaban vs 2·96%warfarin; hazard ratio [HR] 0·94, 95% CI 0·77–1·16) and those without (1·44% vs 1·88%; 0·77, 0·58–1·01; interactionp=0·23). The number of major and non-major clinically relevant bleeding events per 100 person-years in patientstreated with rivaroxaban compared with warfarin was consistent among patients with previous stroke or TIA (13·31%rivaroxaban vs 13·87% warfarin; HR 0·96, 95% CI 0·87–1·07) and those without (16·69% vs 15·19%; 1·10, 0·99–1·21;interaction p=0·08).Interpretation There was no evidence that the relative effi cacy and safety of rivaroxaban compared with warfarin wasdiff erent between patients who had a previous stroke or TIA and those who had no previous stroke or TIA. Theseresults support the use of rivaroxaban as an alternative to warfarin for prevention of recurrent as well as initial strokein patients with AF.