Ischemia Reduction vs. Bleeding After Acute Coronary Syndromes: Minimizing the Trade-Off

Several factor Xa inhibitors are in the pipeline or have been approved for prevention of deep venous thrombosis, atrial fibrillation, or both. However, when tested in patients after an acute coronary syndrome (ACS), these agents have been associated with increased risk for major and intracranial bleeding (JW Cardiol Jul 27 2011). In the manufacturer-sponsored ATLAS ACS 2–TIMI 51 trial, investigators randomized 15,526 patients (mean age, 62; 9% aged ≥75; 25% women) within 7 days after hospital admission for an ACS to standard therapy (including aspirin and, usually, a thienopyridine) plus either placebo or rivaroxaban in one of two doses (2.5 or 5 mg) twice daily.

At a mean follow-up of 13 months, the rate of the composite primary endpoint (death, myocardial infarction, and stroke) was significantly lower in the rivaroxaban group (both dose groups combined) than in the placebo group (8.9% vs. 10.7%); improvement was significant with both doses. The 2.5-mg dose — but not the 5-mg dose — significantly reduced all-cause mortality compared with placebo (2.9% vs. 4.5%). Compared with placebo, rivaroxaban at either dose was associated with significant increases in major bleeding (2.1% vs. 0.6%) and intracranial hemorrhage (0.6% vs. 0.2%). Compared with the 5-mg dose, the 2.5-mg dose produced significantly fewer fatal bleeding events (0.1% vs. 0.4%).