Abstract 10457: Inability of the 150mg Maintenance Dose of Clopidogrel to Prevent Increased Mortality After Drug-eluting Stents in Patients With High Platelet Reactivity on Standard-dose Clopidogrel
In the EXCELSIOR-study, high on-clopidogrel platelet reactivity (HPR) carried an 8-fold increase in the 1-year risk of death (D) and myocardial infarction (MI) after elective percutaneous coronary intervention (PCI) with placement of a drug-eluting stent (DES). We speculated that the increased risk associated with HPR may be corrected by doubling of the maintenance dose (MD) of clopidogrel. We tested this hypothesis in a prospective registry. We enrolled 2,053 consecutive patients with DES placement considered at high risk for stent thrombosis based on procedural and anatomic criteria. In these patients, we assessed HPR by the EXCELSIOR criterion as residual platelet aggregation (RPA) >14% determined by optical aggregometry (ADP 5μM) after loading with clopidogrel 600mg and the first MD of 75mg. We allocated patients with RPA >14% to an intensified treatment regimen of clopidogrel comprising an additional bolus of clopidogrel 300mg and an increased MD of clopidogrel 150mg. Treatment with clopidogrel was continued for at least 6 months after PCI while aspirin was prescribed throughout. Primary endpoint was the composite incidence of death from any cause and myocardial infarction (D&MI) during a follow-up of at least 12 months (mean follow-up 20 months). The study had an 81% power to detect a 4% percent difference in D&MI at a p<0.05. A major proportion of the cohort (n=839; 41%) displayed HPR on clopidogrel at day 1 after PCI. These patients were allocated to the high-dose treatment regimen of clopidogrel (150mg per day). Study endpoints are summarized in the table:
The increase in clopidogrel MD to 150mg failed to correct the increased long-term risk of patients undergoing DES placement with HPR following standard loading and MD. Despite the adjustment of the clopidogrel MD, long-term mortality as well as the combined risk of death and myocardial infarction continued to be increased in patients with HPR as compared to patients with adequate clopidogrel response.
- © 2010 by American Heart Association, Inc.