title: Comparison of the efficacy and safety of two rivaroxaban doses in acute coronary syndrome (from ATLAS ACS 2-TIMI 51).
abstract: 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.
authors.affiliation: TIMI Study Group, Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA. jmega@partners.org
authors.forename: Jessica L
authors.initials: JL
authors.lastname: Mega
authors.forename: Eugene
authors.initials: E
authors.lastname: Braunwald
authors.forename: Stephen D
authors.initials: SD
authors.lastname: Wiviott
authors.forename: Sabina A
authors.initials: SA
authors.lastname: Murphy
authors.forename: Alexei
authors.initials: A
authors.lastname: Plotnikov
authors.forename: Nina
authors.initials: N
authors.lastname: Gotcheva
authors.forename: Mikhail
authors.initials: M
authors.lastname: Ruda
authors.forename: C Michael
authors.initials: CM
authors.lastname: Gibson
mesh_terms: D054058:Acute Coronary Syndrome / Q000188:drug therapy*; D000328:Adult; D000368:Aged; D000925:Anticoagulants / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D023381:Endpoint Determination; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009025:Morpholines / Q000008:administration & dosage*; D000069552:Rivaroxaban; D013876:Thiophenes / Q000008:administration & dosage*; D016896:Treatment Outcome
chemical_list: D000925:Anticoagulants; D009025:Morpholines; D013876:Thiophenes; D000069552:Rivaroxaban