ROCKET AF: rivaroxaban demonstrates efficacy and safety for stroke prevention in atrial fibrillation
ROCKET AF met its primary efficacy endpoint and demonstrated that once-daily rivaroxaban was as effective as warfarin (non-inferior) in preventing thromboembolic events in moderate-to-high risk patients with non-valvular atrial fibrillation (AF) for whom guidelines recommend oral anticoagulation.75
Overall bleeding rates were similar in both study arms but the rivaroxaban group had significantly fewer intracranial haemorrhages and fatal bleeding events.
In conclusion, ROCKET AF showed that once-daily rivaroxaban offers a convenient, safe and effective alternative to warfarin for the prevention of stroke and systemic embolism for patients with AF; importantly, intracranial haemorrhage and fatal bleeding occurred less frequently with rivaroxaban.
Patient demographics
At baseline, patients in the rivaroxaban (N=7131) and warfarin (N=7133) groups were well matched:
- Median age: 73 years75
- Mean CHADS2 score: 3.575
- 55% had experienced a previous stroke or transient ischaemic attack75
- Median creatinine clearance: 67 ml/min75
- 21% had creatinine clearance of 30–49 ml/min104
- Mean time in therapeutic range (INR 2.0–3.0) among patients in the warfarin group: 55%75
The patients enrolled in ROCKET AF were those for whom all guidelines recommend the use of an oral anticoagulant; this study provides insights into patients for whom warfarin management presents a clinical challenge in practice.
Patients were treated for a median of 590 days; median follow-up was 707 days, which included ~117 off-treatment days in patients who discontinued study medication prematurely.
Patients were treated for a median of 590 days; median follow-up was 707 days, which included ~117 off-treatment days in patients who discontinued study medication prematurely.
Primary efficacy endpoint: rivaroxaban demonstrated similar efficacy to warfarin75
ROCKET AF met its primary efficacy endpoint and demonstrated that rivaroxaban was non-inferior to warfarin.
- The primary efficacy analysis (in the per-protocol on-treatment population) showed that the primary endpoint occurred in 1.71%/year in the rivaroxaban arm compared with 2.16%/year with warfarin (hazard ratio=0.79; 95% confidence interval [CI] 0.66–0.96; p<0.001 for noninferiority). This was achieved with a median TTR of 55% in the warfarin arm.
In the intention-to-treat analysis (including on- and off- treatment events), rivaroxaban demonstrated non-inferiority compared with warfarin, but this analysis did not reach statistical significance for superiority (hazard ratio 0.88, 95% CI 0.75-1.03; p<0.001 for non-inferiority).
Safety: similar overall bleeding with fewer ICH and fatal bleeds75
The principal safety outcome – the incidence of the composite of major and non-major clinically relevant bleeding – was similar with both rivaroxaban and warfarin, with important differences in the types of major bleeding events observed.
- Incidence of major bleeding from a gastrointestinal site (upper, lower or rectal) was higher in the rivaroxaban group than in the warfarin group (3.2% vs 2.2% respectively; p<0.001). This accounted for most of the increase in transfusions and haemoglobin concentration falls seen with rivaroxaban
Other safety outcomes75
There were no differences in the values for liver function tests between study arms. Rates of adverse events and serious adverse events were low and similar in the rivaroxaban and warfarin groups. Based on adverse events that occurred in the rivaroxaban group, dyspepsia was not among the 15 most frequent adverse events.
- 75 - Patel MR, Mahaffey KW, Garg J et al. Rivaroxaban versus warfarin in nonvalvular atrial fibrillation. N Engl J Med 2011;365:883–891.
- 104 - Fox KAA, Piccini JP, Wojdyla D et al. Prevention of stroke and systemic embolism with rivaroxaban compared with warfarin in patients with non-valvular atrial fibrillation and moderate renal impairment. Eur Heart J 2011;32:2387–2394.
- Atrial fibrillation
- A heart rhythm disorder where chambers in the upper heart (atria) beat more rapidly than those in the lower section of the heart. Blood is not pumped out of the upper chambers completely during beating, and may pool and form a clot. A stroke results if a section of clot dislodges from the upper chambers and becomes lodged in the brain.
- Efficacy
- The ability of a drug to produce the desired effect.
