Little is known about the association between clopidogrel use and long-term outcomes after stent implantation for acute coronary syndromes (ACS) in clinical practice.

This retrospective cohort study included patients with ACS receiving drug-eluting stent (DES) or bare-metal stent (BMS) and discharged from all Veterans Health Administration hospitals from 2003 to 2004. Clopidogrel use was assessed by pharmacy dispensing data. Multivariable Cox regression assessed the association between clopidogrel discontinuation and outcomes with clopidogrel use as a time-varying covariate and adjusting for demographics, comorbidities, hospital presentation, and treatment variables. Median follow-up was 538 days.

Of 1455 patients with ACS, 65.8% received BMS and 34.2% received DES. The median number of days of clopidogrel use was 299. In multivariable analysis, clopidogrel discontinuation was associated with higher all-cause mortality (hazard ratio [HR] 2.40, 95% confidence interval [CI] 1.61-3.58). The findings were consistent for patients receiving BMS (HR 2.65, 95% CI 1.59-4.42) or DES (HR 2.00, 95% CI 1.06-3.75) and for the outcomes of acute myocardial infarction (AMI) and AMI or mortality. When follow-up was divided into 6-month intervals, the association between clopidogrel discontinuation and higher mortality remained consistent up to 18 months after hospital discharge. In secondary analysis of patients who were event-free at 6 months, clopidogrel discontinuation was associated with higher risk for AMI among patients receiving DES (HR 3.57, 95% CI 1.13-11.3) compared with BMS (HR 1.26, 95% CI 0.58-2.74).

Clopidogrel discontinuation after extended use was still associated with increased mortality risk. Clinical trials are urgently needed to define the optimal duration of clopidogrel therapy after stent implantation for ACS.