title: Effect of prior clopidogrel use on outcomes in medically managed acute coronary syndrome patients.
abstract: 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.
  
  
  
  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.
  
  
  
  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).
  
  
  
  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.
  
  
  
  NCT00699998.
authors.affiliation: National Heart Centre Singapore, Singapore Duke-NUS Graduate Medical School, Singapore.
authors.forename: Chee Tang
authors.initials: CT
authors.lastname: Chin
authors.affiliation: Department of Medicine, Albany Stratton VA Medical Center and Albany Medical Center, Albany Medical College, Albany, New York, USA.
authors.forename: William E
authors.initials: WE
authors.lastname: Boden
authors.affiliation: Division of Cardiology, Department of Medicine, Duke University School of Medicine, Durham, North Carolina, USA Duke Clinical Research Institute, Durham, North Carolina, USA.
authors.forename: Matthew T
authors.initials: MT
authors.lastname: Roe
authors.affiliation: Duke Clinical Research Institute, Durham, North Carolina, USA.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Neely
authors.affiliation: Duke Clinical Research Institute, Durham, North Carolina, USA.
authors.forename: Megan L
authors.initials: ML
authors.lastname: Neely
authors.affiliation: Department of Cardiology, Hospital Central "Dr. Morones Prieto", San Luis Potosi, Mexico.
authors.forename: Jose L
authors.initials: JL
authors.lastname: Leiva-Pons
authors.affiliation: Pontificia Universidad Católica de Chile, Santiago, Chile.
authors.forename: Ramón
authors.initials: R
authors.lastname: Corbalán
authors.affiliation: Department of Cardiology, Heart Institute, Bikur Cholim Campus, Shaare Zedek Medical Center, Jerusalem, Israel.
authors.forename: Shmuel
authors.initials: S
authors.lastname: Gottlieb
authors.affiliation: Milpark Hospital, Johannesburg, South Africa.
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Dalby
authors.affiliation: Division of Cardiology, Department of Medicine, Canadian VIGOUR Centre, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Paul W
authors.initials: PW
authors.lastname: Armstrong
authors.affiliation: Centre for Chronic Disease Control and Public Health Foundation of India, New Delhi, India.
authors.forename: Dorairaj
authors.initials: D
authors.lastname: Prabhakaran
authors.affiliation: Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, UK.
authors.forename: Keith A A
authors.initials: KA
authors.lastname: Fox
authors.affiliation: Green Lane Cardiovascular Service, Auckland City Hospital, Auckland, New Zealand.
authors.forename: Harvey D
authors.initials: HD
authors.lastname: White
authors.affiliation: Division of Cardiology, Department of Medicine, Duke University School of Medicine, Durham, North Carolina, USA Duke Clinical Research Institute, Durham, North Carolina, USA.
authors.forename: E Magnus
authors.initials: EM
authors.lastname: Ohman
authors.affiliation: Eli Lilly and Company, Indianapolis, Indiana, USA.
authors.forename: Kenneth J
authors.initials: KJ
authors.lastname: Winters
authors.affiliation: Department of Cardiology, University Hospital Jean Minjoz, Besançon, France.
authors.forename: Francois
authors.initials: F
authors.lastname: Schiele
mesh_terms: D054058:Acute Coronary Syndrome / Q000150:complications / Q000175:diagnosis / Q000188:drug therapy* / Q000401:mortality; D000368:Aged; D001241:Aspirin / Q000008:administration & dosage; D000077144:Clopidogrel; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D006470:Hemorrhage / Q000139:chemically induced; D006760:Hospitalization; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000209:etiology; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects; D000068799:Prasugrel Hydrochloride / Q000008:administration & dosage; D016016:Proportional Hazards Models; D018570:Risk Assessment; D012307:Risk Factors; D020521:Stroke / Q000209:etiology; D013988:Ticlopidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D010975:Platelet Aggregation Inhibitors; D000077144:Clopidogrel; D000068799:Prasugrel Hydrochloride; D013988:Ticlopidine; D001241:Aspirin