ROCKET AF

Rivaroxaban – Once daily, oral, direct factor Xa inhibition Compared with vitamin K antagonism for prevention of stroke and Embolism Trial in Atrial Fibrillation (2010)

Condition

Prevention of VTE in patients with AF

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Objective

To establish the non-inferiority of rivaroxaban compared with warfarin in patients with non-valvular AF who have a history of stroke or at least 2 additional independent risk factors for future stroke (heart failure, hypertension, age =75 years, diabetes mellitus)

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Trial design

Prospective, randomized, double-blind, double-dummy phase III study with parallel groups
Active treatment: rivaroxaban 20 mg p.o. once daily plus warfarin placebo (n=7131)
Control treatment: warfarin once daily titrated to a target INR of 2.0–3.0 plus rivaroxaban placebo (n=7133)

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Endpoints

Primary efficacy endpoint: composite of all-cause stroke and non-CNS systemic embolism
Primary safety endpoint: composite of major and clinically relevant nonmajor bleeding events
Secondary efficacy endpoints: all-cause death, vascular death, and myocardial infarction

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Trial participants

14,264 patients (mean age 73 years) with non-valvular AF documented on =2 episodes, with 55% having had a prior TIA or stroke and =90% having hypertension. In addition, 87% of the patients had a CHADS2 score of 3 or higher

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Results

Efficacy outcome: Overall, rivaroxaban was non-inferior to warfarin in terms of the primary end point (event rate 1.71 vs. 2.16; p<0.001), and superior to warfarin when investigators analyzed the risk of stroke and non-CNS embolism in patients who remained on treatment over the course of the 40-month trial (event rate 1.70 vs. 2.15; p=0.015). Rivaroxaban was not superior to warfarin in the stricter intent-to-treat analysis (event rate 2.12 vs. 2.42; p=0.117)
Safety outcome: On the principal safety measure of major and non-major clinically relevant bleeding events, rivaroxaban was similar compared with warfarin (14.91% vs. 14.52%, p=0.442). Rates of major bleeding were also comparable between rivaroxaban and warfarin (3.60% vs. 3.45%, p=0.576). Patients treated with rivaroxaban had fewer intracranial hemorrhages (0.49% vs. 0.74%, p=0.019), fewer critical organ bleeds (0.82% vs. 1.18%, p=0.007) and lower bleeding-related deaths (0.24% vs. 0.48%, p=0.003) than those on warfarin

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Summary

Efficacy: Overall, rivaroxaban was non-inferior to warfarin in terms of the primary endpoint (composite of stroke and non-CNS embolism), and was superior to warfarin in patients who remained on treatment over the course of the 40-month trial. In the stricter intent-to-treat analysis, rivaroxaban was non-inferior to warfarin, but did not achieve superiority
Safety outcome: The rates of major and non-major clinically relevant bleeding were comparable in both groups, with less fatal bleeding and intracranial hemorrhage observed among patients treated with rivaroxaban

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Reference

(1) The Executive Steering Committee, on behalf of the ROCKET AF Study Investigators. Rivaroxaban-once daily, oral, direct factor Xa inhibition compared with vitamin K antagonism for prevention of stroke and embolism trial in atrial fibrillation: rationale and design of the ROCKET AF study. Am Heart J 2010;159:340-347.e1
(2) Mahaffey KW on behalf of the ROCKET AF Study Investigators. American Heart Association Scientific Sessions 2010; Late Breaking Clinical Trials, Nov 15th 2010
(3) ClinicalTrials.gov (NCT00403767)

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Corresponding author

Manesh R. Patel, MD, Duke Clinical Research Institute, Durham, NC 27705, e-mail: patel017@mc.duke.edu

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