NEW YORK (Reuters Health) – After a first myocardial infarction, treatment with a calcium-channel blocker (CCB) does not appear to diminish the efficacy of clopidogrel, according to results of a Danish nationwide cohort study.

“The results of this study do not support safety concerns with concomitant treatment with CCBs and clopidogrel,” the researchers conclude in the January 25 issue of the Journal of the American College of Cardiology, available online now.

CCBs and clopidogrel are metabolized by the same hepatic cytochrome P-450 enzyme – CYP3A4. There is concern, therefore, that CCBs can interfere with the metabolism of clopidogrel to its active form and thereby reduce the clinical efficacy of this widely-used antiplatelet agent.

Based on their study, Dr. Jonas B. Olesen and colleagues from the department of cardiology, Copenhagen University Hospital Gentofte, in Hellerup, Denmark, conclude that this potential drug interaction is “unlikely to have clinical significance.”

Using the Danish National Patient Registry, they identified 56,800 patients hospitalized with a first MI between 2000 and 2006. The cohort was divided into patients treated with clopidogrel (n = 24,923) and without clopidogrel (n = 31,877) and followed for 1 year after discharge.

Overall, 13,380 study subjects were treated with a CCB.

The Cox proportional hazard analyses showed an increased risk of the composite end point of cardiovascular death, rehospitalization for MI or stroke, associated with CCB therapy in patients treated with clopidogrel (HR, 1.15) and without clopidogrel (HR, 1.05).

However, the hazard rate ratio for interaction between CCBs and clopidogrel was 1.08, “indicating no significant effect modification of CCBs and clopidogrel treatment on the primary study outcome,” the researchers report.

Similar results were achieved in analyses looking at individual components of the composite end point.

This was true, the researchers say, for “all the main CCB pharmacological subclasses, in both high- and low-dose CCB treatment and in different patient subpopulations.”

“We found that the use of CCBs was associated with increased cardiovascular risk after MI independent of concomitant treatment with clopidogrel,” they report. This may be explained by unmeasured confounders, such as diabetes mellitus or renal failure, both of which were more common in patients treated with CCBs.

“What’s unique about our analyses,” Dr. Olesen noted in an e-mail to Reuters Health, “is that they are carried out in a nationwide (Danish) population. Consequently, we have no selection bias regarding socioeconomic status, etc., and, hence, the results represent the average person with ischemic heart disease.”

In addition, due to the “very large” size of the study sample, all analyses were “very powerful and, therefore, an eventual difference in risk (interaction between clopidogrel and CCBs) would have been detected if it was present,” Dr. Olesen added.

“Concomitant treatment with clopidogrel and CCBs is safe when treatment is indicated,” the researcher concludes.

J Am Coll Cardiol 2011;57:409-417.