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Calcium-Channel Blockers Do Not Alter the Clinical Efficacy of Clopidogrel After Myocardial Infarction: A Nationwide Cohort Study
Study Questions:
Do calcium channel blockers (CCBs) reduce the clinical efficacy of clopidogrel?
Methods:
Patients surviving 30 days after a first myocardial infarction (MI) in the period 2000-2006 in Denmark were identified and divided into patients treated with and without clopidogrel. The risk of a composite of cardiovascular death, MI, or stroke and the risk of the individual components of the composite endpoint and all-cause death associated with CCBs were analyzed with multivariable Cox proportional hazard models, and in univariate propensity score-matched models.
Results:
A total of 56,800 patients were included, of whom 24,923 were treated with clopidogrel and 13,380 with CCBs. In the Cox analyses, the risk of the composite endpoint associated with CCBs was increased in both patients treated and not treated with clopidogrel, with a hazard ratio of 1.15 (95% confidence interval [CI], 1.07-1.24) and 1.05 (95% CI, 1.01-1.11), respectively. The increased risk was independent of clopidogrel use; the hazard rate ratio was 1.08 (95% CI, 0.99-1.18). Analyses of all additional adverse endpoints and propensity score-matched models provided similar results.
Conclusions:
The authors concluded that the clinical efficacy of clopidogrel in patients with a recent MI is not modified by concomitant CCB treatment.
Perspective:
Clopidogrel is a prodrug that requires metabolic conversion via cytochrome P-450 enzymes to its active metabolite. Thus, there is concern that patients with hypomorphic P-450 gene variants or patients taking medications that reduce function of enzymes required for clopidogrel conversion may not receive adequate platelet inhibition with clopidogrel. The clinical consequences of these interactions remain controversial. CCBs are metabolized by the same enzymes as clopidogrel and have been shown to interfere with platelet inhibition by clopidogrel in some studies. Although the current study is observational in nature and the indications for treatment (or no treatment) with CCBs and clopidogrel are unclear, this study does not support a clinically relevant interaction between clopidogrel use and concomitant CCB treatment in patients following an MI.
Keywords: Myocardial Infarction, Stroke, Propensity Score, Platelet Aggregation Inhibitors, Denmark, Cytochromes, Ticlopidine, Confidence Intervals, Calcium Channel Blockers
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