Use of clopidogrel and calcium channel blockers and risk of major adverse cardiovascular events.

The CYP3A4 inhibition by calcium channel blockers (CCBs) may attenuate the effectiveness of clopidogrel. Using time-varying drug exposure ascertainment, we examined whether CCB use modified the association between clopidogrel use and major adverse cardiovascular events (MACE) after coronary stent implantation. We conducted this population-based cohort study in western Denmark (population 3 million) using medical databases. We identified all 13,001 patients with coronary stent implantation between 2002 and 2005 and their comorbidities. During 12-month follow-up, we tracked the use of clopidogrel and CCBs and the rate of MACE (composite of myocardial infarction, ischaemic stroke, stent thrombosis, target lesion revascularization, or cardiac death). We used Cox regression to compute hazard ratios, controlling for potential confounders. Overall, the 12-month risk for MACE was 14·5%. The rate was 130 per 1000 person years for concomitant clopidogrel and CCB use, 106 for clopidogrel without CCB use, 213 for CCB without clopidogrel use, and 248 for no use of either drug. The adjusted hazard ratio for MACE comparing clopidogrel use with nonuse was 0·52 [95% confidence interval (CI): 0·42-0·64] for CCB users and 0·48 (95% CI: 0·42-0·54) for nonusers, yielding an interaction effect, i.e. relative rate increase, of 1·09 (95% CI: 0·86-1·38). The adjusted hazard ratio for MACE comparing CCB use with nonuse was 1·06 (95% CI: 0·89-1·25) among clopidogrel users. Concomitant use of CCBs as a class did not modify the protective effect of clopidogrel and was not associated with increased cardiovascular risk among patients using clopidogrel after coronary stent implantation.