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Effect of prior clopidogrel use on outcomes in medically managed acute coronary syndrome patients
  1. Chee Tang Chin1,2,
  2. William E Boden3,
  3. Matthew T Roe4,5,
  4. Benjamin Neely5,
  5. Megan L Neely5,
  6. Jose L Leiva-Pons6,
  7. Ramón Corbalán7,
  8. Shmuel Gottlieb8,
  9. Anthony J Dalby9,
  10. Paul W Armstrong10,
  11. Dorairaj Prabhakaran11,
  12. Keith A A Fox12,
  13. Harvey D White13,
  14. E Magnus Ohman4,5,
  15. Kenneth J Winters14,
  16. Francois Schiele15
  1. 1National Heart Centre Singapore, Singapore
  2. 2Duke-NUS Graduate Medical School, Singapore
  3. 3Department of Medicine, Albany Stratton VA Medical Center and Albany Medical Center, Albany Medical College, Albany, New York, USA
  4. 4Division of Cardiology, Department of Medicine, Duke University School of Medicine, Durham, North Carolina, USA
  5. 5Duke Clinical Research Institute, Durham, North Carolina, USA
  6. 6Department of Cardiology, Hospital Central “Dr. Morones Prieto”, San Luis Potosi, Mexico
  7. 7Pontificia Universidad Católica de Chile, Santiago, Chile
  8. 8Department of Cardiology, Heart Institute, Bikur Cholim Campus, Shaare Zedek Medical Center, Jerusalem, Israel
  9. 9Milpark Hospital, Johannesburg, South Africa
  10. 10Division of Cardiology, Department of Medicine, Canadian VIGOUR Centre, University of Alberta, Edmonton, Alberta, Canada
  11. 11Centre for Chronic Disease Control and Public Health Foundation of India, New Delhi, India
  12. 12Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, UK
  13. 13Green Lane Cardiovascular Service, Auckland City Hospital, Auckland, New Zealand
  14. 14Eli Lilly and Company, Indianapolis, Indiana, USA
  15. 15Department of Cardiology, University Hospital Jean Minjoz, Besançon, France
  1. Correspondence to Dr Matthew T. Roe, Associate Professor of Medicine, Division of Cardiology, Department of Medicine, Duke University School of Medicine, DUMC Box 3850, Durham, NC 27710, USA; matthew.roe{at}


Objective We investigated whether prior clopidogrel influenced long-term ischaemic and bleeding risks and modified the randomised treatment effect of clopidogrel versus prasugrel among medically managed patients with acute coronary syndromes (ACS) treated with dual antiplatelet therapy.

Methods Medically managed patients with ACS in the Targeted Platelet Inhibition to Clarify the Optimal Strategy to Medically Manage Acute Coronary Syndromes (TRILOGY ACS) trial were randomised to clopidogrel versus prasugrel (plus aspirin), stratified by prior clopidogrel use. From the analysis population (n=8927), we compared two groups: ‘clopidogrel in-hospital (n=6513)’ (clopidogrel started ≤72 h of presentation for index ACS event) and ‘prior-clopidogrel (n=2414)’ (on clopidogrel ≥5 days before index hospitalisation). Treatment-related differences in ischaemic (all-cause death, cardiovascular (CV) death, myocardial infarction (MI), stroke and the composite of CV death/MI/stroke) and bleeding outcomes (severe/life-threatening or moderate bleeding events based on Global Use of Strategies to Open Occluded Coronary Arteries (GUSTO) criteria) through 30 months were analysed between patients in the two groups.

Results Compared with ‘clopidogrel in-hospital,’ ‘prior clopidogrel’ patients were younger (median 64 years vs 66 years, p<0.001), more likely to have prior CV events/revascularisation, and had a higher frequency of CV death, MI or stroke through 30 months (20.8% vs 18.2%, p=0.002), with no difference in bleeding events (2.3% vs 3.4%, p=0.50). Randomised treatment effect (prasugrel vs clopidogrel) was similar for ischaemic and bleeding outcomes in both groups (all pinteraction>0.05).

Conclusions Patients receiving clopidogrel before admission for ACS and subsequently treated only medically are at higher risk for CV events versus those not previously receiving clopidogrel. More potent antiplatelet inhibition with prasugrel versus clopidogrel did not significantly reduce this risk.

Trial registration number NCT00699998.

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