Author + information
- Received March 3, 2013
- Revision received April 2, 2013
- Accepted May 1, 2013
- Published online August 27, 2013.
- ∗Division of Cardiology, University of Colorado School of Medicine, Aurora, Colorado
- †Denver Health Medical Center, Denver, Colorado
- ‡Colorado Prevention Center, Aurora, Colorado
- §Division of Cardiology, Cedars-Sinai Medical Center, Los Angeles, California
- ‖David Geffen School of Medicine at UCLA, Los Angeles, California
- ↵∗Reprint requests and correspondence
: Dr. Mori J. Krantz, Denver Health Medical Center, 777 Bannock Street, MC 0960, Denver, Colorado 80204.
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.
Opinions expressed in this article are those of the authors and do not necessarily reflect the opinions of the Food and Drug Administration (FDA) or any other branch of the U.S. Department of Health and Human Services. Drs. Krantz and Kaul participated as voting members at the May 23, 2012, FDA Cardiovascular and Renal Drugs Advisory Committee meeting. Dr. Krantz has served as a consultant for Novo Nordisk, Abbott Vascular, Cameron Pharmaceuticals, and CoLucid Pharmaceuticals. Dr. Kaul owns stock in Johnson & Johnson.
- Received March 3, 2013.
- Revision received April 2, 2013.
- Accepted May 1, 2013.
- American College of Cardiology Foundation