title: The ATLAS ACS 2-TIMI 51 trial and the burden of missing data: (Anti-Xa Therapy to Lower Cardiovascular Events in Addition to Standard Therapy in Subjects With Acute Coronary Syndrome ACS 2-Thrombolysis In Myocardial Infarction 51).
abstract: Rivaroxaban is a factor Xa inhibitor that was recently reviewed by the Food and Drug Administration as a potential therapy to reduce the risk of recurrent atherothrombotic events in patients with acute coronary syndromes. Approval of this drug would represent a paradigm shift away from dual antiplatelet therapy toward long-term triple antithrombotic therapy. However, to date, no other experimental anticoagulant agent has demonstrated a favorable risk-benefit profile in this population, in part because of the expected increased risk in major bleeding by combining aspirin, a P2Y12 receptor inhibitor, and an anticoagulant. Approvability of rivaroxaban was considered largely on the basis of the ATLAS ACS 2-TIMI 51 (Anti-Xa Therapy to Lower Cardiovascular Events in Addition to Standard Therapy in Subjects With Acute Coronary Syndrome ACS 2-Thrombolysis In Myocardial Infarction 51) trial, which demonstrated a significant reduction in a composite of cardiovascular death, myocardial infarction, and stroke. Although the primary efficacy endpoint was met, a substantial amount of missing data was observed. We discuss the impact of missing data in this trial, its implications for informative censoring of safety events (major bleeding), and implications for future cardiovascular outcomes trials.
authors.affiliation: Division of Cardiology, University of Colorado School of Medicine, Aurora, Colorado, USA. mori.krantz@dhha.org
authors.forename: Mori J
authors.initials: MJ
authors.lastname: Krantz
authors.forename: Sanjay
authors.initials: S
authors.lastname: Kaul
mesh_terms: D054058:Acute Coronary Syndrome / Q000150:complications / Q000188:drug therapy*; D000925:Anticoagulants / Q000009:adverse effects / Q000627:therapeutic use*; D003328:Coronary Thrombosis / Q000209:etiology / Q000517:prevention & control; D004311:Double-Blind Method; D015951:Factor Xa / Q000009:adverse effects / Q000627:therapeutic use; D065427:Factor Xa Inhibitors; D006801:Humans; D009025:Morpholines / Q000009:adverse effects / Q000627:therapeutic use*; D009203:Myocardial Infarction / Q000209:etiology / Q000517:prevention & control; D016032:Randomized Controlled Trials as Topic / Q000592:standards* / Q000706:statistics & numerical data*; D015203:Reproducibility of Results; D000069552:Rivaroxaban; D013876:Thiophenes / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome; D014481:United States; D014486:United States Food and Drug Administration
chemical_list: D000925:Anticoagulants; D065427:Factor Xa Inhibitors; D009025:Morpholines; D013876:Thiophenes; D000069552:Rivaroxaban; D015951:Factor Xa
keywords: ACS; CRDAC; CV; Cardiovascular and Renal Drugs Advisory Committee; FDA; Food and Drug Administration; MACE; MI; acute coronary syndrome(s); cardiovascular; informative censuring; major adverse cardiac event(s); missing data; myocardial infarction; rivaroxaban; triple antithrombotic therapy