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.
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 (P2Y12reaction 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.
Medisch Centrum Alkmaar, Alkmaar, The Netherlands.
Jan H
JH
Cornel
Duke Clinical Research Institute, Durham, NC.|Division of Cardiology, Department of Medicine, Duke University Medical Center, Durham, NC.
E Magnus
EM
Ohman
Duke Clinical Research Institute, Durham, NC.
Benjamin
B
Neely
Eli Lilly and Company, Indianapolis, IN.
Joseph A
JA
Jakubowski
Brigham and Women's Hospital Heart & Vascular Center and Harvard Medical School, Boston, MA.
Deepak L
DL
Bhatt
Green Lane Cardiovascular Service, Auckland City Hospital, Auckland, New Zealand.
Harvey D
HD
White
Division of Cardiology, Azienda Ospedaliero-Universitaria di Parma, Italy.
Diego
D
Ardissino
Centre for Cardiovascular Science, University of Edinburgh, Scotland, UK.
Keith A A
KA
Fox
Centre for Chronic Disease Control and Public Health Foundation of India, New Delhi, India.
Dorairaj
D
Prabhakaran
Canadian VIGOUR Centre and Division of Cardiology, University of Alberta, Edmonton, Alberta, Canada.
Paul W
PW
Armstrong
Department of Cardiology, Lund University, Lund, Sweden.
David
D
Erlinge
Sinai Center for Thrombosis Research, Baltimore, MD.
Udaya S
US
Tantry
Sinai Center for Thrombosis Research, Baltimore, MD.
Paul A
PA
Gurbel
Duke Clinical Research Institute, Durham, NC matthew.roe@duke.edu.|Division of Cardiology, Department of Medicine, Duke University Medical Center, Durham, NC.
Matthew T
MT
Roe
D054058:Acute Coronary Syndrome / Q000188:drug therapy*; D000368:Aged; D000789:Angina, Unstable / Q000188:drug therapy*; D001241:Aspirin / Q000627:therapeutic use; D001792:Blood Platelets / Q000502:physiology*; D000077144:Clopidogrel; D004359:Drug Therapy, Combination; D005260:Female; D006470:Hemorrhage / Q000139:chemically induced*; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D000072658:Non-ST Elevated Myocardial Infarction / Q000188:drug therapy*; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use*; D010979:Platelet Function Tests; D000068799:Prasugrel Hydrochloride / Q000627:therapeutic use; D016016:Proportional Hazards Models; D016032:Randomized Controlled Trials as Topic; D013988:Ticlopidine / Q000031:analogs & derivatives / Q000627:therapeutic use
D010975:Platelet Aggregation Inhibitors; D000077144:Clopidogrel; D000068799:Prasugrel Hydrochloride; D013988:Ticlopidine; D001241:Aspirin
DAPT; hemorrhage; platelet