article45

ROCKET AF

"Rivaroxaban versus Warfarin in Nonvalvular Atrial Fibrillation". The New England Journal of Medicine. 2011. 365:883-891. PubMed • Full text • PDF

1 Clinical Question
2 Bottom Line
3 Major Points
4 Guidelines
5 Design
6 Population
6.1 Inclusion Criteria
6.2 Exclusion Criteria
6.3 Baseline Characteristics
7 Interventions
8 Outcomes
8.1 Primary Outcomes
8.2 Secondary Outcomes
8.3 Safety
9 Criticisms
10 Funding
11 Further Reading

Clinical Question

Is rivaroxaban noninferior or superior to warfarin for the prevention of stroke or systemic embolism in patients with nonvalvular atrial fibrillation?

Bottom Line

In patients with nonvalvular atrial fibrillation, rivaroxaban is noninferior to warfarin for the prevention of stroke or systemic embolism. There were no significant differences in rates of major and clinically relevant nonmajor bleeding, although intracranial and fatal bleeding occurred less frequently with rivaroxaban.

Major Points

Guidelines

As of 2011, no guidelines have been published incorporating the results of this trial.

Design

- Multicenter, randomized, double-blind, double-dummy, event-driven trial
- N=14,264 patients
- Interventions:
- Rivaroxaban 20 mg daily (15 mg daily if creatinine clearance 30-49 ml/min)
- Dose-adjusted warfarin (target INR of 2.0 to 3.0)
- Mean follow-up: 1.94 years

Population

- Inclusion Criteria: Nonvalvular atrial fibrillation and increased risk of stroke
- Exclusion Criteria: Active bleeding, liver disease, high bleeding risk, and others
- Baseline Characteristics: A median age of 73 years, 39.7% female, history of hypertension in 90.5%, 62.5% with heart failure

Interventions

- Fixed-dose rivaroxaban vs. adjusted-dose warfarin
- INR monitoring with a blinded point-of-care device

Outcomes

Primary Outcomes
- Stroke or systemic embolism: Rivaroxaban 1.7% per year vs. Warfarin 2.2% per year (HR 0.79, P<0.001 for noninferiority)

Secondary Outcomes
- Major and nonmajor clinically relevant bleeding: Rivaroxaban 14.9% per year vs. Warfarin 14.5% per year (HR 1.03, P=0.44)
- Intracranial hemorrhage: Less frequent with rivaroxaban

Safety
- Bleeding and hemorrhage: Similar major bleeding rates for both groups, with less fatal bleeding in the rivaroxaban group

Criticisms

- Lower than anticipated INR control in warfarin group
- Rivaroxaban associated with a higher rate of gastrointestinal bleeding

Funding

Supported by Johnson & Johnson Pharmaceutical Research and Development and Bayer HealthCare.