Bayer 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.
"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", said Professor Werner Hacke, Chair of the Department of Neurology at the University of Heidelberg, Germany, and member of the ROCKET AF Executive Steering Committee. "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 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.
ROCKET AF is the seventh consecutive Phase III trial in the ongoing rivaroxaban global development program that has demonstrated either superiority (RECORD1, 2, 3, 4, EINSTEIN-EXTENSION and ROCKET AF), or non-inferiority (EINSTEIN-DVT). The RECORD trial program compared rivaroxaban to enoxaparin in the prevention of venous thromboembolism in more than 12,500 patients undergoing elective hip or knee replacement surgery. The multinational Phase III EINSTEIN-DVT study investigated a new single-drug approach with rivaroxaban compared with initial enoxaparin treatment, followed by a vitamin K antagonist in a randomized, open-label non-inferiority study involving more than 3,400 patients with acute symptomatic DVT, but without any symptoms of PE. EINSTEIN-Extension evaluated the efficacy and safety of rivaroxaban compared to placebo in the secondary prevention of recurrent symptomatic venous blood clots, by extending preventative treatment by 6 or 12 months beyond a previously completed regimen of 6 or 12 months of therapy, and enrolled approximately 1,200 patients with symptomatic DVT or PE.
About Atrial Fibrillation
AF is the most common sustained cardiac rhythm disorder and affects more than 2.3 million people in the U.S. and up to 6 million people in Europe. In patients with AF, the irregular heartbeat makes them vulnerable to the formation of a blood clot in the atria, which can travel to the brain, potentially resulting in a stroke. Strokes cause damage to the brain, and can lead to physical and behavioral impairment, or even death. People with AF are at a five-fold increased risk for stroke compared with the general population - about one-third of them will suffer from a stroke.
About ROCKET AF
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. It has a rapid onset of action with a predictable dose response and high bioavailability, no requirement for coagulation monitoring, as well as a limited potential for food and drug interactions. Rivaroxaban is marketed under the brand name Xarelto® for VTE prevention in adult patients following elective hip or knee replacement surgery, and it is the only new oral anticoagulant that has consistently demonstrated superior efficacy over enoxaparin for this indication. Xarelto® is approved in more than 100 countries worldwide and has been successfully launched in more than 75 countries by Bayer HealthCare.
The extensive clinical trial program supporting rivaroxaban makes it the most studied oral, direct Factor Xa inhibitor in the world today. More than 65,000 patients are participating in the rivaroxaban clinical development program evaluating the product in the prevention and treatment of a broad range of acute and chronic blood-clotting disorders, including VTE treatment, secondary prevention of acute coronary syndrome, and VTE prevention in hospitalized, medically ill patients.
If approved by the FDA, Ortho-McNeil, a division of Ortho-McNeil-Janssen Pharmaceuticals, Inc. (a Johnson & Johnson Company), will commercialize rivaroxaban in the U.S. The U.S. Bayer HealthCare sales force will support the Ortho-McNeil sales force by detailing rivaroxaban in designated hospital accounts. Bayer HealthCare is exclusively responsible for the marketing of rivaroxaban in countries outside the U.S.
To learn more about thrombosis, please visit http://www.thrombosisadviser.com.
About Bayer HealthCare
The Bayer Group is a global enterprise with core competencies in the fields of health care, nutrition and high-tech materials. Bayer HealthCare, a subgroup of Bayer AG with annual sales of more than EUR 15.9 billion (2009), is one of the world’s leading, innovative companies in the healthcare and medical products industry and is based in Leverkusen, Germany. The company combines the global activities of the Animal Health, Consumer Care, Medical Care and Pharmaceuticals divisions. Bayer HealthCare’s aim is to discover and manufacture products that will improve human and animal health worldwide. Bayer HealthCare has a global workforce of 53.400 employees and is represented in more than 100 countries. Find more information at http://www.bayerhealthcare.com.