Renal function and outcomes in acute coronary syndrome: impact of clopidogrel

INTRODUCTION: Patients with renal dysfunction are more prone to bleeding when receiving antithrombotic drugs. The aim of the study was to assess the impact of clopidogrel on safety and efficacy in patients with renal dysfunction in non-ST elevation acute coronary syndromes. METHODS AND RESULTS: Patients in the Clopidogrel in Unstable Angina to Prevent Recurrent Events (CURE) trial were analysed to assess the relationship of chronic kidney disease to cardiovascular outcomes. Renal function was estimated by the glomerular filtration rate computed from the baseline serum creatinine measurements in 12 253 (97.5%) patients enrolled in the trial. Patients were grouped into tertiles of glomerular filtration rate. The primary outcome (cardiovascular death, myocardial infarction, stroke combined) occurred more frequently in the lowest glomerular filtration rate tertile. The bleeding risk was also significantly increased in patients in this tertile, compared with the other two. The beneficial effect of adding clopidogrel to standard treatment in non-ST elevation acute coronary syndrome was observed in all three tertiles of renal function {(lower third relative risk (RR)=0.89 [95% confidence interval (CI) 0.76-1.05]; medium third RR=0.68 (95% CI 0.56-0.84); upper third RR=0.74 (95% CI 0.60-0.93) (P for heterogeneity=0.11)}. Clopidogrel treatment significantly increased the risk of minor bleeding in all tertiles of renal function. The risk of major or life-threatening bleeding increased moderately with the addition of clopidogrel to standard treatment [lower third RR=1.12 (95% CI 0.83-1.51); medium third RR=1.4 (95% CI 0.97-2.02); upper third RR=1.83 (95% CI 1.23-2.73)], but this did not appear to be greatest in those with the lowest renal function. CONCLUSIONS: Even mild chronic kidney disease worsens the prognosis in patients with non-ST elevation acute coronary syndromes. Clopidogrel was beneficial and safe in patients with and without chronic kidney disease.