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Bayer today announced the results from the pivotal, double-blind Phase III, ROCKET AF trial.
In the study, rivaroxaban demonstrated superiority to warfarin in reducing the risk of stroke and non-CNS systemic embolism in patients with atrial fibrillation (AF).
Importantly, rates of bleeding were similar to warfarin, and bleeding events most concerning to physicians and patients, including intracranial hemorrhage, critical organ bleed, and bleeding-related death, were significantly lower in the rivaroxaban group.
The results were presented today as a late-breaker at the American Heart Association Scientific Sessions 2010 in Chicago, USA.
Professor Werner Hacke, Chair of the Department of Neurology at the University of Heidelberg, Germany, and member of the ROCKET AF Executive Steering Committee, said: “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,” he said.
With 14,264 patients randomised, 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 hemorrhagic stroke, one of the most severe types of 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 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. Rates of hemoglobin 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, it is exciting to have an alternative which was documented in this study to be effective with no increase in significant bleeding,” said Robert M. Califf, M.D., study co-chairman and Vice Chancellor for Clinical Research from Duke University.