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Astrid Kranz
Alexander Siedler


Clinical Articles, Lead Article

Rocket AF: Rivaroxaban comparable safety with Warfarin

The ROCKET AF study results were presented as a late-breaker at the recent American Heart Association Scientific Sessions 2010 in Chicago, USA.

They show the superiority of once-daily rivaroxaban over warfarin in protecting AF patients from stroke and non-CNS systemic embolism.  Rivaroxaban  also demonstrates comparable major and non-major clinically relevant bleeding, as well as significantly lower rates of intracranial haemorrhage vs. warfarin.

ROCKET AF is the seventh consecutive Phase III trial in the ongoing rivaroxaban global development program that has demonstrated either superiority, or non-inferiority compared to standard of care.

rocket02Professor Werner Hacke, Chair of the Department of Neurology at the University of Heidelberg, Germany, and member of the ROCKET AF Executive Steering Committee gave the following statement: “Atrial fibrillation and stroke devastate the lives of millions of patients and their families worldwide every year. Anticoagulation with warfarin is effective in preventing strokes in patients with atrial fibrillation and has been the standard of care for more than half a century. However, its use in clinical practice is associated with many limitations…The ROCKET AF study has shown that once-daily rivaroxaban promises patients improved protection from stroke, with good safety and added convenience.”

With 14,264 patients randomized, ROCKET AF is the largest double-blind study undertaken in the prevention of stroke in patients with AF, comparing once-daily rivaroxaban to dose-adjusted warfarin. For the primary efficacy endpoint, rivaroxaban was superior to warfarin, delivering a 21% relative risk reduction in stroke and non-CNS systemic embolism in the pre-specified on treatment population (1.70% vs. 2.15%, p=0.015).

Additionally, in the intent to treat (ITT) population which followed all patients randomised in the trial until its completion, whether or not they completed the full course of therapy or switched to other options, rivaroxaban showed comparable benefits to warfarin (2.12% vs. 2.42%, p<0.001 for non-inferiority). This result indicates that the treatment benefits compared to warfarin were sustained as long as the patients received rivaroxaban.

In addition, significantly fewer cases of haemorrhagic stroke were observed in patients on rivaroxaban (0.26% vs. 0.44% p=0.024). Compared to warfarin, rivaroxaban also showed numerically fewer cases of myocardial infarction (0.91% vs. 1.12%, p=0.121), and an observed reduction in rates of all-cause mortality (1.87% vs. 2.21%, p=0.073).

The improved protection of patients provided by rivaroxaban in ROCKET AF was not associated with an increase in bleeding. 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).

Importantly, patients treated with rivaroxaban had fewer intracranial haemorrhages (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. Rates of haemoglobin drop (2.77% vs. 2.26%, p=0.019) and transfusion requirements (1.65% vs. 1.32%, p=0.044) were increased when compared to patients who received warfarin.

The frequency of abnormal laboratory values of liver function was balanced between the treatment groups and there was no signal for serious liver damage attributable to rivaroxaban observed in the trial.

Rivaroxaban was well tolerated in the study, and rates of discontinuation due to adverse events were similar to those seen for patients on warfarin. Rivaroxaban, administered once daily, without the need for routine laboratory coagulation monitoring delivered improved protection, simplified dosing and good tolerability.

“Given the prevalence and morbidity associated with atrial fibrillation, and the well-known difficulties with warfarin use,” said study co-chairman Robert M. Califf, M.D., “it is exciting to have an alternative which was documented in this study to be effective with no increase in significant bleeding.”


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) was a prospective, randomized, double-blind, double-dummy parallel group outcomes study comparing once-daily rivaroxaban (20 mg, or 15 mg for patients with moderate renal impairment) with dose-adjusted warfarin in 14,264 patients with non-valvular atrial fibrillation who were at risk for stroke or non-CNS systemic embolism.

This was an event-driven trial, which ended when the pre-specified number of efficacy events was accumulated. The primary objective of ROCKET AF was to demonstrate the efficacy of once-daily rivaroxaban as non-inferior to well controlled warfarin in the prevention of stroke and non-CNS systemic embolism in patients with non-valvular AF. The principal safety measure of ROCKET AF was the composite of major plus non-major clinically relevant bleeding events. The patients with AF evaluated in ROCKET AF typify those who are treated today by physicians with an anticoagulant to help reduce the risk of stroke.

About Rivaroxaban

Rivaroxaban is a novel oral anticoagulant that was invented in Bayer HealthCare’s Wuppertal laboratories in Germany, and is being jointly developed by Bayer HealthCare and Johnson & Johnson Pharmaceutical Research & Development, L.L.C.

Find more information at

Published on: December 9, 2010

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  • ArrhythmiaAlliance
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