Effect of prior clopidogrel use on outcomes in medically managed acute coronary syndrome patients

• Published in: Heart (British Cardiac Society) Vol. 102; no. 15; pp. 1221 - 1229
• Main Authors: Chin, Chee Tang, Boden, William E, Roe, Matthew T, Neely, Benjamin, Neely, Megan L, Leiva-Pons, Jose L, Corbalán, Ramón, Gottlieb, Shmuel, Dalby, Anthony J, Armstrong, Paul W, Prabhakaran, Dorairaj, Fox, Keith A A, White, Harvey D, Ohman, E Magnus, Winters, Kenneth J, Schiele, Francois
• Format: Journal Article
• Language: English
• Published: England BMJ Publishing Group LTD 01.08.2016
• Subjects: Acute Coronary Syndrome - complications; Acute Coronary Syndrome - diagnosis; Acute Coronary Syndrome - drug therapy; Acute Coronary Syndrome - mortality; Acute coronary syndromes; Aged; Aspirin; Aspirin - administration & dosage; Blood platelets; Clinical outcomes; Double-Blind Method; Drug Administration Schedule; Drug dosages; Drug Therapy, Combination; Female; Heart attacks; Hemorrhage - chemically induced; Hospitalization; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Myocardial Infarction - etiology; Patients; Platelet Aggregation Inhibitors - administration & dosage; Platelet Aggregation Inhibitors - adverse effects; Prasugrel Hydrochloride - administration & dosage; Proportional Hazards Models; Risk Assessment; Risk Factors; Statistical analysis; Stroke; Stroke - etiology; Ticlopidine - administration & dosage; Ticlopidine - adverse effects; Ticlopidine - analogs & derivatives; Time Factors; Treatment Outcome
• ISSN: 1355-6037; 1468-201X
• DOI: 10.1136/heartjnl-2015-308840

ObjectiveWe 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.MethodsMedically 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.ResultsCompared 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).ConclusionsPatients 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 numberNCT00699998.