Added to standard medical treatment, the oral anticoagulant rivaroxaban lowered overall risk of mortality, myocardial infarction and stroke in acute coronary syndrome patients, according to late-breaking research presented at the American Heart Association's Scientific Sessions 2011 and simultaneously published in the New England Journal of Medicine.

"Despite our best efforts at treatment following a recent heart attack or unstable angina, patients still face a 10 percent or higher risk of a repeat heart attack, stroke or death one year later," said C. Michael Gibson, M.D., senior investigator of the TIMI Study Group, Harvard Medical School, and the Principal Investigator in the ATLAS ACS studies of rivaroxaban for this indication.

"We know that people with a heart attack or unstable angina make too much thrombin, an enzyme that forms clots. We looked at whether reducing the production of thrombin with rivaroxaban reduces the risk of death, stroke or heart attack."

Researchers analyzed more than 15,000 people hospitalized with a recent myocardial infarction or unstable angina in the Anti-Xa Therapy to Lower Cardiovascular Events in Addition to Standard Therapy in Subjects with Acute Coronary Syndrome-Thrombolysis in Myocardial Infarction 51 Trial (ATLAS ACS 2-TIMI 51). Study participants were randomized to receive either standard care along with rivaroxaban [2.5 mg rivaroxaban (n=5,174), 5.0 mg rivaroxaban (n=5,176)] or standard care with placebo (n=5,176).

Researchers followed these patients for a mean of 13 months and found:

• Those who took rivaroxaban had a 16 percent reduced risk of cardiovascular death, stroke or heart attack compared to patients who didn't.
• The risk of death, including all causes of death, was reduced more than 30 percent with the addition of rivaroxaban.
• Stent thrombosis was reduced by 31 percent in patients taking rivaroxaban compared to patients who didn't.
• As with other types of anticoagulants, more internal bleeding occurred among those who took rivaroxaban than those who took placebo and the increase in TIMI major bleeding was significant. However, there was no increase in fatal bleeding.

In terms of the individual doses, the lower dose showed the best results.

Rivaroxaban and other new oral anticoagulants have demonstrated the ability to reduce strokes in patients with atrial fibrillation, but their use in patients with acute coronary syndrome has had mixed results. Because these patients are often on other anticoagulants, the bleeding risk has been very high.

"Our findings are important because blocking the production of thrombin is an important new way to improve acute coronary syndrome patients' long-term risk of death, stroke and heart attack after being hospitalized with an acute coronary syndrome," Gibson said.

The authors conclude that very low dose rivaroxaban poses an effective treatment to minimize cardiovascular events in patients with acute coronary syndromes.

Co-authors are Eugene Braunwald, M.D., and Jessica Mega, M.P.H., M.D.

Johnson and Johnson and Bayer HealthCare funded the study.