WEDNESDAY, June 17 (HealthDay News) -- The new anti-clotting pill rivaroxaban (Xarelto) lowers the risk of stroke, heart attack and death in patients who have had a heart attack or suffer from unstable angina, a new trial shows.
Rivaroxaban is a pill that blocks factor Xa, which is involved in blood clotting. In earlier studies, the drug was effective in preventing venous thromboembolism (blood clots in the legs) after orthopedic surgery, although some increased risk in bleeding episodes was seen. In this phase II trial, researchers tested the safety and efficacy of the drug at various doses.
"The use of an oral factor Xa inhibitor in patients stabilized after an acute coronary syndrome increases bleeding in a dose-dependent manner, and might reduce major ischemic outcomes," said lead researcher Dr. Jessica L. Mega, from the Cardiovascular Division at Brigham and Women's Hospital in Boston. "On the basis of these observations, a phase III study of low-dose rivaroxaban as adjunctive therapy in these patients is underway."
The report is published in the June 17 online edition of The Lancet.
In March, a U.S. Food and Drug Administration advisory panel voted 15-2 that rivaroxaban, a long-sought alternative to commonly used blood thinners that have to be injected and are tricky to monitor, had benefits that outweighed its bleeding risks. Although the FDA is not bound by the panel's decision, it typically follows suit on these recommendations.
For the study, Mega's group treated 3,491 patients who had had heart attacks or unstable angina with either aspirin or aspirin plus the anti-clotting drug clopidogrel (Plavix).
The patients were then randomly assigned to a placebo or rivaroxaban, at doses ranging from 5 milligrams to 20 milligrams a day. The researchers looked for any significant bleeding and deaths, heart attacks and stroke.
There was an increase in bleeding episodes with rivaroxaban. Over six months, the researchers found that risk increased with dosage. At 5 milligrams, the risk increased 2.2 times, while the 20-milligram dose raised the risk fivefold.
However, patients receiving rivaroxaban had a 21 percent reduction in heart attacks, strokes, ischemic events and deaths compared with patients taking placebo. For heart attack, stroke and death alone, the risk was reduced by 31 percent compared with placebo, the researchers found.
"In this study, rivaroxaban was associated with a dose-dependent increase in clinically significant bleeding events, with a trend towards a reduction in the primary efficacy endpoint of death, myocardial infarction, stroke or severe recurrent ischemia requiring revascularization," Mega and colleagues wrote. "Regarding the main secondary efficacy endpoint, rivaroxaban reduced the rate of death, myocardial infarction or stroke."
Dr. Hitinder S. Gurm, from the University of Michigan Cardiovascular Center and co-author of an accompanying journal editorial, said the study showed no benefit in patients who are using aspirin and Plavix, although there was a suggestion of a benefit when the drug was used with aspirin alone.
"This study was a dose-finding study; it would be premature to assess the future of this drug in patients with acute coronary syndrome based on this trial, and the little bit of data that we have does not suggest the drug would provide a major benefit in patients who are already on contemporary therapy -- with the caveat that we need a larger trial to confirm or refute this," Gurm said.
Dr. Richard C. Becker, director of the Cardiovascular Thrombosis Center at Duke University Medical Center, said this study is another step in the search for an anti-clotting drug to replace warfarin for many patients. Warfarin is an effective drug, but requires constant monitoring to assure that patients are receiving a dose that is not too low, which is ineffective, or too high, which increases the risk of bleeding.
"The trends toward benefit with rivaroxaban, as a fixed-dose, direct and oral factor Xa inhibitor, provide a sound rationale to pursue a path of further investigation," Becker said.
The dose-related bleeding risk supports a strategy of lower doses than would be used for other potential indications for the drug, such as atrial fibrillation and venous thrombosis, he said.
"In the next several years, the field will have a wealth of information on antithrombotic therapies, providing a platform to determine optimal treatment in a wide range of patients with acute coronary syndrome," Becker said.
For more information on anticoagulants, visit the American Heart Association.
SOURCES: Jessica L. Mega, M.D., Cardiovascular Division, Brigham and Women's Hospital, Boston; Hitinder S. Gurm, M.D., director, inpatient services, division of cardiovascular medicine, University of Michigan Cardiovascular Center, Ann Arbor; Richard C. Becker, M.D., director, Cardiovascular Thrombosis Center, Duke University Medical Center, Durham, N.C.; June 17, 2009, The Lancet, online