The clinical efficacy of clopidogrel (Plavix, Bristol-Myers Squibb/Sanofi-Aventis) in patients with a recent MI is not modified by concomitant calcium-channel blocker (CCB) treatment, and the potential drug interaction is unlikely to have clinical significance, according to research published Jan. 25 in the Journal of the American College of Cardiology.
CCBs inhibit a variety of cytochrome P-450 enzymes, some of which contribute to clopidogrel metabolic activation, which have led some to question whether this interaction diminishes the efficacy of clopidogrel, according to the study authors.
Jonas B. Olesen, MB, from the department of cardiology at the Copenhagen University Hospital Gentofte in Hellerup, Denmark, identified all patients surviving 30 days after a first-time MI in the period 2000 to 2006 in Denmark by individual-level linkage of nationwide administrative registers. A total of 56,800 patients were included, of whom 24,923 were treated with clopidogrel and 13,380 with CCBs.
The cohort was divided into patients treated with and without clopidogrel and followed for one year after discharge. The researchers analyzed 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.
In the Cox analyses, the investigators found that 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 and 1.05, respectively.
“The increased risk was independent of clopidogrel use; the hazard rate ratio was 1.08,” the authors wrote. “Analyses of all additional adverse endpoints and propensity score-matched models provided similar results.”
Olesen and colleagues said that their results suggest the absence of "a clinically significant interaction between CCBs and clopidogrel and that the increased risk associated with CCBs may be explained by unmeasured confounders.” They also found that CCBs were more frequently administered to patients with diabetes mellitus or renal failure.
The results of this study do not support safety concerns with concomitant treatment with CCBs and clopidogrel, the authors concluded.