Comparison of the Efficacy and Safety of Two Rivaroxaban Doses in Acute Coronary Syndrome (from ATLAS ACS 2–TIMI 51)

The dosing of anticoagulants is critical when balancing efficacy and safety. The Anti-Xa Therapy to Lower Cardiovascular Events in Addition to Aspirin With/Without Thienopyridine Therapy in Subjects With Acute Coronary Syndrome 2–Thrombolysis In Myocardial Infarction 51 (ATLAS ACS 2–TIMI 51) trial was designed to evaluate 2 low doses of rivaroxaban compared with placebo in patients with recent acute coronary syndromes being treated with antiplatelet therapies. Because the 2 doses significantly reduced the primary efficacy end point, a further comparison of the 2 treatment strategies was deemed important. In total, 15,526 patients were randomized to twice-daily rivaroxaban 2.5 mg, rivaroxaban 5 mg, or placebo. Comparing the 2 active doses, there were no significant differences between 2.5 and 5 mg for the primary efficacy end point of cardiovascular death, myocardial infarction, or stroke (9.1% vs 8.8%, p = 0.89), myocardial infarction (6.1% vs 4.9%, p = 0.23), or stent thrombosis (2.2% vs 2.3%, p = 0.59). However, there was a divergence in cardiovascular death, which included ischemic and hemorrhagic events, with the 2.5-mg dose resulting in lower rates than the 5-mg dose (2.7% vs 4.0%, p = 0.009). Notably, with 2.5 versus 5 mg, there were fewer study drug discontinuations (p = 0.004) and fewer non–coronary artery bypass grafting TIMI major or minor bleeds (p = 0.021) and fatal bleeds (p = 0.044). Of the patients who died, 8 in the 2.5-mg group and 20 in the 5-mg group experienced non–coronary artery bypass grafting TIMI major or minor bleeding events before death. In conclusion, the 2 doses of rivaroxaban reduced cardiovascular events in patients with recent acute coronary syndromes treated with antiplatelet therapies; however, the 2.5-mg dose was associated with lower mortality and fewer bleeding complications than the 5-mg dose. Thus, the addition of rivaroxaban 2.5 mg twice daily offers a more favorable balance of efficacy and safety in patients with recent acute coronary syndromes.