NEW YORK (Reuters Health) – The platelet inhibition caused by clopidogrel is reduced when the drug is coadministered with calcium-channel blockers, Austrian researchers report.

Dr. Bernd Jilma and colleagues, from the Medical University of Vienna, hypothesized that there would be an interaction between clopidogrel and CCBs because they both are involved with the CYP3A4 enzyme. Specifically, CCBs inhibit CYP3A4, while clopidogrel is activated by the enzyme.

In a study reported in the Journal of the American College of Cardiology for November 4, the researchers evaluated this interaction in 200 patients with coronary artery disease undergoing percutaneous coronary intervention. Forty-five patients used clopidogrel and a CCB, while the remaining 155 used clopidogrel alone.

Platelet function was assessed using vasodilator-stimulated phosphoprotein phosphorylation and aggregometry.

Platelet reactivity was significantly higher in patients receiving clopidogrel and a CCB than in those receiving just clopidogrel (p = 0.001). Likewise, decreased platelet inhibition was more common when both drugs were given (p = 0.008). Multivariate analysis confirmed that CCB use was an independent predictor of reduced platelet inhibition with clopidogrel.

Compared with patients taking just clopidogrel, those taking clopidogrel and a CCB were also found to have higher adenosine diphosphate-induced platelet aggregation (p = 0.046).

No significant effect on platelet aggregation was seen when clopidogrel was incubated in vitro with a CCB, suggesting that the interaction is, in fact, mediated by the CYP3A4 enzyme.

Lastly, 25% of clopidogrel/CCB-treated patients, but just 8% of clopidogrel-only patients, experienced the composite endpoint of death from cardiovascular causes, non-fatal MI, stent thrombosis, and revascularization (p = 0.001). This difference was solely due to a higher rate of revascularization in the clopidogrel/CCB group.

In a related editorial, Dr. Neal S. Kleiman, from the Methodist DeBakey Heart and Vascular Center in Houston, comments that although the present findings cannot be considered definitive proof of a clinical interaction between clopidogrel and CCBs, “they certainly should give the clinician reason for pause.”

Reference:
Journal of the American College of Cardiology, November 4, 2008