Rivaroxaban Once-Daily Oral Direct Factor Xa Inhibition Compared With Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation [ROCKET AF]
The goal of the trial was to evaluate treatment with the direct factor Xa inhibitor rivaroxaban compared with warfarin among patients with atrial fibrillation (AF). Rivaroxaban will be noninferior to warfarin in preventing stroke and embolism.
The trial was done in patients with AF at increased risk for stroke were randomized to rivaroxaban 20 mg oral daily (n = 7,131) versus warfarin with target international normalized ratio (INR) 2-3 (n = 7,133).
There was overall, 14,171 patients were randomized. In the rivaroxaban group, the mean age was 73 years, 40% were women, mean CHADS2 score was 3.5, 40% had diabetes, and 55% had prior stroke, transient ischemic attack (TIA), or systemic embolism.
The primary outcome per 100 patient-years, stroke, or non‒central nervous system systemic embolism occurred in 1.7 of the rivaroxaban group versus 2.2 of the warfarin group (p for noninferiority < 0.001, p for superiority by intention to treat 0.12). By on-treatment analysis, rivaroxaban was superior to warfarin (p = 0.015).
By on-treatment analysis, vascular death, stroke, or embolism per 100 patient-years occurred in 3.1 versus 3.6 (p = 0.034), non‒central nervous system embolism occurred in 0.04 versus 0.2 (p = 0.003), myocardial infarction occurred in 0.9 versus 1.1 (p = 0.12), and all-cause mortality occurred in 1.9 versus 2.2 (p = 0.07), respectively, for rivaroxaban versus warfarin.
Major and non-major clinically relevant bleeding per 100 patient-years occurred in 14.9 versus 14.5 (p = 0.44), intracranial hemorrhage occurred in 0.5 versus 0.7 (p = 0.019), study drug discontinuation occurred in 16% versus 15%, and any serious adverse event occurred in 37% versus 38%, respectively.
Major and non-major clinically relevant bleeding per 100 patient-years occurred in 14.9 versus 14.5 (p = 0.44), intracranial hemorrhage occurred in 0.5 versus 0.7 (p = 0.019), study drug discontinuation occurred in 16% versus 15%, and any serious adverse event occurred in 37% versus 38%, respectively.
The authors concluded that among patients with AF and increased risk for stroke, the use of the direct Xa inhibitor rivaroxaban was noninferior to warfarin. Rivaroxaban (on-treatment analysis) was associated with reduced incidence of the primary outcome without an excess of major bleeding or serious adverse events. In addition to rivaroxaban, an alternative to warfarin for AF patients includes the direct thrombin inhibitor dabigatran studied in the RE-LY trial. The signal for increased myocardial infarction observed with dabigatran was not seen with rivaroxaban.
Reference:
Presented by Dr. Kenneth Mahaffey at the American Heart Association Scientific Sessions, Chicago, IL, November 15, 2010
http://www.cardiosource.org/Science-And-Quality/Clinical-Trials/R/ROCKET-AF.aspx?WT.nv=CSourceNews&WT.pub=CSourceNews101115
