ROCKET AF trial, rivaroxaban vs warfarin in Afib

Background

Noninferiority phase III RCT (ROCKET AF), N=14,264, nonvalvular atrial fibrillation with CHADS2 ≥2 (prior stroke/TIA/embolism, or ≥2 of HF with EF ≤35%, ≥75 y/o, DM). Exclusions: CrCl <30 mL/min, liver disease or ALT >3×ULN, significant mitral stenosis, prosthetic valve, atrial myxoma, LV thrombus, CVA <15 days, TIA <3 days.

Interventions and follow up

Arm A: rivaroxaban 20 mg daily (15 mg if CrCl 30-50 mL/min)
Arm B: warfarin, INR 2.0-3.0
Primary endpoint: composite of stroke (ischemic or hemorrhagic) and systemic embolism
mFollow up: 707 days

Results

ITT stroke or systemic embolism: 2.1 vs 2.4 events/yr, HR 0.88, 95%CI 0.75-1.03, P<.001 for noninferiority
Per-protocol stroke or systemic embolism: 1.7 vs 2.2 events/yr, HR 0.79, 95%CI 0.66-0.96, P<.001 for noninferiority
MI: 0.9 vs 1.1 per 100 patient-yr, HR 0.81, 95%CI 0.63-1.06, P=.12
All-cause mortality: 1.9 vs 2.2 per 100 patient-yr

Adverse events

Major + clinically relevant nonmajor bleeding (A vs B): 20.7% vs 20.3%
Major bleeding: 5.6% vs 5.4%
Drug discontinuation: 23.7% vs 22.2%

Conclusions

Rivaroxaban was noninferior to warfarin for prevention of stroke or systemic embolism in nonvalvular atrial fibrillation, with similar bleeding.

Key Limitations

Noninferiority design; relatively low warfarin time-in-therapeutic-range (~55%); higher-risk cohort than other AF DOAC trials; once-daily dosing of a short-acting agent debated; no superiority on ITT.

Clinical Context

Pivotal trial supporting FDA approval of rivaroxaban for stroke prevention in nonvalvular AF (2011). Established rivaroxaban as a once-daily DOAC alternative to warfarin; guideline-endorsed for nonvalvular AF.

References