Rivaroxaban is as effective as warfarin in preventing blood clots and stroke and does not increase bleeding risk in patients with atrial fibrillation.
A new anti-clotting drug, rivaroxaban, is as effective as warfarin in preventing blood clots and stroke and does not increase bleeding risk among patients with the most common form of irregular heartbeat, atrial fibrillation, according to clinical trial results presented Monday in Chicago at the American Heart Association Scientific Sessions 2010.
“The main implication is that we have an alternative to warfarin,” said Robert M. Califf, MD, co-principal investigator of the study and vice chancellor for clinical research at Duke University School of Medicine. “Equally important, there was no increase in bleeding, so we have a drug you can take once a day, without monitoring, which is at least as good as warfarin and causes no additional risk.”
Rivaroxaban, developed by Johnson & Johnson Pharmaceutical Research & Development and Bayer Health AG, is one of several new drugs now in clinical trials that seek to replace warfarin, which for more than 50 years has been the primary anti-clotting medication available. Warfarin requires frequent monitoring because it can interact with other medications, and even with certain foods to cause potentially excessive bleeding. In fact, in 2006, the FDA added a black box warning to warfarin due to the risk of bleeding to death. Rivaroxaban is an oral anticoagulant being evaluated for a range of disorders in which blood clotting plays a major role.
The Stroke Prevention Using the Oral Direct Factor Xa Inhibitor Rivaroxaban Compared with Warfarin in Patients with Nonvalvular Atrial Fibrillation (ROCKET AF) trial has one of the largest patient populations of its kind and included 14,264 patients with atrial fibrillation unrelated to heart valve dysfunction at more than 1,100 hospitals in 45 countries. The median age was 73 and 43.5 percent were 75 years or older. Forty percent were women and 83 percent were white. More than half had suffered a stroke or period of decreased blood flow to the brain.
Participants were randomized to receive either 20 milligrams of rivaroxaban daily or an appropriately adjusted dose of warfarin. The study was conducted from December 2006 to May 2010 and treatment averaged 19 months. It was double-blind and double-dummy -- researchers were simulating with placebo both drugs so the investigator couldn’t tell which drug the patient is on. “That is a very important part of the rigor of this trial,” Califf said.
In the primary analysis measuring what happened to research participants while they were actually taking the study drug, those taking rivaroxaban compared with warfarin had fewer strokes and blood clots to other parts of the body. With rivaroxaban, there were 1.71 events per 100 patient-years (188 patients) and with warfarin 2.16 (241 patients). Major bleeding complications were comparable in both treatment groups.
Death from any cause occurred slightly less frequently among rivaroxaban patients at a rate of 4.52 per 100-patient years (582 patients) versus 4.91 per 100-patient years (632 patients) among those on warfarin.
Both drugs prevent dangerous clots by blocking the action of vitamin-K-dependent proteins called clotting factors; rivaroxaban targets a specific clotting factor called Xa. While some clotting is necessary to prevent bleeding, too much can bring on life-threatening clots in patients with atrial fibrillation.
More than 2.5 million Americans live with irregular heartbeat, which increases the risk of stroke by four to five times and causes 15-20 percent of all blood-clot related strokes. The disorder causes more than 11,000 deaths in the US each year.