Lack of impact of calcium-channel blockers on the pharmacodynamic effect and the clinical efficacy of clopidogrel after drug-eluting stenting

Am Heart J. 2011 Mar;161(3):605-10. doi: 10.1016/j.ahj.2010.11.010. Epub 2011 Jan 31.

Abstract

Background: Clopidogrel is a prodrug that is metabolized to its active metabolite by the hepatic cytochrome P450 system. Calcium-channel blockers (CCBs) are metabolized by the same pathway and may therefore attenuate the antiplatelet effect of clopidogrel. The aim of this study was to assess the impact of CCB therapy on the pharmacodynamic effect and the clinical efficacy of clopidogrel after drug-eluting stent placement.

Methods: A total of 1,608 consecutive patients were previously enrolled in a study that aimed to assess the relation between platelet reactivity and outcomes after coronary stenting. Here, this cohort was analyzed according to concomitant CCB therapy at admission. The primary pharmacodynamic end point was adenosine diphosphate-induced platelet aggregation (in AU · min) with multiple electrode platelet aggregometry after loading with 600 mg clopidogrel. The primary clinical end point was combination of death or definite stent thrombosis (ST) at 30 days. Secondary end points included definite ST alone, myocardial infarction, stroke, and death.

Results: Two hundred thirty-two patients (14.4%) were on CCBs on admission. Compared with patients with CCB medication, patients without CCB medication showed no significant difference in median [interquartile range] platelet aggregation values (232 [142-365] vs 223 [141-368] AU · min, P = .53). There was also no significant difference regarding the clinical end point of death or ST (2 [0.9%] vs 16 [1.2%], odds ratio 0.74, 95% CI 0.17-3.2, P = .69) between both groups.

Conclusion: In our population, concomitant CCB therapy did not alter clopidogrel-mediated platelet aggregation and did not have a measurable impact on ST and mortality after coronary stenting.

MeSH terms

  • Aged
  • Calcium Channel Blockers / pharmacology*
  • Clopidogrel
  • Coronary Angiography
  • Coronary Artery Disease / diagnostic imaging
  • Coronary Artery Disease / drug therapy*
  • Coronary Thrombosis / epidemiology
  • Drug Synergism
  • Drug-Eluting Stents
  • Endpoint Determination
  • Female
  • Humans
  • Male
  • Platelet Aggregation / drug effects*
  • Platelet Aggregation Inhibitors / pharmacology*
  • Platelet Function Tests
  • Ticlopidine / analogs & derivatives*
  • Ticlopidine / pharmacology

Substances

  • Calcium Channel Blockers
  • Platelet Aggregation Inhibitors
  • Clopidogrel
  • Ticlopidine