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

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Background--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. Methods and Results--We analyzed 2428medicallymanaged acute coronary syndromes patients fromthe 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 orminor bleeding. Exploratory analyses used 3-level composites that incorporatedmild andminimalGUSTOand TIMI events.Continuousmeasures of PRUs (per 10-unit decrease)were not independently associatedwith the 2-levelGUSTO (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 PRUcut point of 75 differentiated bleeding riskwith the 3-level composites ofGUSTO(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). Conclusions--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.


  • Jan H. Cornel
  • E. Magnus Ohman
  • Benjamin Neely
  • Joseph A. Jakubowski
  • Deepak L. Bhatt
  • Harvey D. White
  • Diego Ardissino
  • Keith A.A. Fox
  • Dorairaj Prabhakaran
  • Paul W. Armstrong
  • David Erlinge
  • Udaya S. Tantry
  • Paul A. Gurbel
  • Matthew T. Roe
External organisations
  • Duke University
  • Lilly Research Laboratories
  • Brigham and Women's Hospital / Harvard Medical School
  • Auckland City Hospital
  • University of Edinburgh
  • University of Alberta
  • Northwest Hospital Group, Alkmaar
  • Parma University Hospital
  • Public Health Foundation of India
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Cardiac and Cardiovascular Systems


  • DAPT, Hemorrhage, Platelet
Original languageEnglish
Article numbere003977
JournalJournal of the American Heart Association
Issue number11
Publication statusPublished - 2016
Publication categoryResearch