Relationship of Platelet Reactivity With Bleeding Outcomes During Long-Term Treatment With Dual Antiplatelet Therapy for Medically Managed Patients With Non-ST-Segment Elevation Acute Coronary Syndromes.

Abstract

The relationship between "on-treatment" low platelet reactivity and longitudinal risks of major bleeding dual antiplatelet therapy following acute coronary syndromes remains uncertain, especially for patients who do not undergo percutaneous coronary intervention.We analyzed 2428 medically managed acute coronary syndromes patients from the Targeted Platelet Inhibition to Clarify the Optimal Strategy to Medically Manage Acute Coronary Syndromes (TRILOGY ACS) trial who had serial platelet reactivity measurements (P2Y12 reaction units; PRUs) and were randomized to aspirin+prasugrel versus aspirin+clopidogrel for up to 30 months. Contal's method was used to determine whether a cut point for steady-state PRU values could distinguish high versus low bleeding risk using 2-level composites: Global Use of Strategies to Open Occluded Coronary Arteries (GUSTO) severe/life-threatening or moderate bleeding unrelated to coronary artery bypass grafting (CABG) and non-CABG Thrombolysis In Myocardial Infarction (TIMI) major or minor bleeding. Exploratory analyses used 3-level composites that incorporated mild and minimal GUSTO and TIMI events. Continuous measures of PRUs (per 10-unit decrease) were not independently associated with the 2-level GUSTO (adjusted hazard ratio [HR], 1.01; 95% CI, 0.96-1.06) or TIMI composites (1.02; 0.98-1.07). Furthermore, no PRU cut point could significantly distinguish bleeding risk using the 2-level composites. However, the PRU cut point of 75 differentiated bleeding risk with the 3-level composites of GUSTO (26.5% vs 12.6%; adjusted HR, 2.28; 95% CI, 1.77-2.94; P<0.001) and TIMI bleeding events (25.9% vs 12.2%; adjusted HR, 2.30; 95% CI, 1.78-2.97; P<0.001).Among medically managed non-ST-segment elevation acute coronary syndromes patients receiving prolonged dual antiplatelet therapy, PRU values were not significantly associated with the long-term risk of major bleeding events, suggesting that low on-treatment platelet reactivity does not independently predict serious bleeding risk.URL: http://www.clinicaltrials.gov. Unique identifier: NCT00699998.

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10.1161/JAHA.116.003977

Publication Info

Cornel, Jan H, E Magnus Ohman, Benjamin Neely, Joseph A Jakubowski, Deepak L Bhatt, Harvey D White, Diego Ardissino, Keith AA Fox, et al. (2016). Relationship of Platelet Reactivity With Bleeding Outcomes During Long-Term Treatment With Dual Antiplatelet Therapy for Medically Managed Patients With Non-ST-Segment Elevation Acute Coronary Syndromes. Journal of the American Heart Association, 5(11). 10.1161/JAHA.116.003977 Retrieved from https://hdl.handle.net/10161/20592.

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Ohman

Erik Magnus Ohman

Professor of Medicine

Dr. Ohman, Professor of Medicine, received medical degrees from the Royal College of Surgeons in Ireland and the National University of Ireland (1984, Fellowship 1984-1987), and completed his training in cardiology at Duke University (1987-1991), where he has remained on faculty. In 2001, he became Chief of Cardiology at the University of North Carolina at Chapel Hill, where he founded the UNC Heart Center and became its first director. In 2005 he returned to Duke to pursue his interest in advanced coronary disease as the Director of the Program for Advanced Coronary Disease. Since that time, he has been appointed to Associate Director of the Duke Heart Center, the Kent and Siri Rawson Director for the Program for Advanced Coronary Disease, and most recently, Vice-Chair of Development and Innovation in the Department of Medicine.

Dr. Ohman’s clinical and research interests include interventional cardiology and high-risk supported PCI, and treatment of patients with advanced/complex coronary disease. He has researched how to improve patient care through the use of guidelines-based therapies and adherence, and examining global cardiovascular risk and health. He has been a participant on numerous guidelines writing committees, served on the ACC/AHA oversight committee for guidelines development, and has served on the steering committees for trials on ST-elevation myocardial infarction and non-ST-elevation ACS. He is a consultant to the National Institutes of Health, and a consultant for the FDA Advisory Panel for Cardiovascular Devices. 

Dr. Ohman has published over 600 peer-reviewed papers and three books in cardiovascular medicine. He holds three U.S. patents in reperfusion therapy. He is an associate editor for the American Heart Journal and serves on the editorial boards of the Journal of the American College of Cardiology and the American Journal of Cardiology.  He is a Fellow of the Royal College of Physicians in Ireland, the Royal Society of Medicine (U.K.), the European Society of Cardiology, the Society of Cardiac Angiography and Interventions, and the American College of Cardiology. 

Paul Wayne Armstrong

Adjunct Professor in the Department of Medicine

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