Rivaroxaban Reduces Death Rates in ACS Patients

Orlando—The anticlotting drug rivaroxaban added to standard medical treatment lowered the risk of cardiovascular (CV) death, myocardial infarction (MI), and stroke in acute coronary syndrome (ACS) patients, but was associated with an increase in thrombolysis in MI (TIMI) major bleeding, according to C. Michael Gibson, MS, MD, who presented the results of the ATLAS ACS 2-TIMI 51 (Anti-Xa Therapy to Lower Cardiovascular Events in Addition to Standard Therapy with Acute Coronary Syndrome-Thrombolysis in Myocardial Infarction 51) trial at the AHA meeting. This study was also simultaneously published online in the New England Journal of Medicine [10.1056/NEJMoa1112277]. “Despite our best efforts at treatment following a recent heart attack or unstable angina, patients still face a 10% or higher risk of repeat heart attack, stroke, or death 1 year later,” explained Dr. Gibson. ATLAS ACS 2-TIMI 51 was a phase 3, randomized, double-blind, interventional, efficacy and safety trial that included >15,000 patients with recent ACS. The aim of the study was to determine whether rivaroxaban along with standard care reduces the risk of CV death, MI, or stroke in patients 1 to 7 days following an ACS event compared with placebo. Patients were randomized to receive twice-daily doses of either 2.5 mg (n=5174) or 5 mg (n=5176) of rivaroxaban or placebo (n=5176) for a mean of 13 months and up to 31 months. The primary end point was a composite of CV death, MI, or stroke. Two-year Kaplan-Meier estimates showed that, together, both doses of rivaroxaban reduced the risk for CV death, MI, and stroke, compared with placebo (8.9% vs 10.7%; hazard ratio [HR], 0.84; 95% confidence interval [CI], 0.74-0.96; P=.008, respectively). Furthermore, rivaroxaban at both doses was associated with a reduced risk for stent thrombosis (2.3% vs 2.9%; HR, 0.69; 95% CI, 0.51-0.93; P=.02, respectively). Rivaroxaban demonstrated significant improvement in reducing the risk of CV death, MI, and stroke at the 2.5-mg dose compared with placebo (9.1% vs 10.7%; P=.02), and in the 5-mg dose compared with placebo (8.8% vs 10.7%; P=.03). The 2.5-mg dose was also associated with a decrease in the rate of death from CV causes (2.7% vs 4.1%; P=.002) and death from any cause (2.9% vs 4.5%; P=.002). A survival benefit was not seen, however, with the 5-mg dose. The risk for non–coronary artery bypass grafting (CABG) major bleeding was increased in the rivaroxaban group versus placebo (2.1% vs 0.6%; HR, 3.96; 95% CI, 2.46-6.38; P<.001). In the comparison between the 2 doses of rivaroxaban, the rates of TIMI major bleeding that was not related to CABG tended to be lower in patients receiving the 2.5-mg dose than in those receiving the 5-mg dose (1.8% vs 2.4%; P=.12), and the lower dose resulted in significantly lower rates of TIMI minor bleeding (0.9% vs 1.6%; P=.046), TIMI bleeding requiring medical attention (12.9% vs 16.2%; P<.001), and fatal bleeding (0.1% vs 0.4%; P=.04). “Very low dose of rivaroxaban 2.5 mg twice daily, in addition to antiplatelet therapies, represents an effective strategy to reduce cardiovascular events in patients with a recent ACS,” Dr. Gibson concluded.