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

https://doi.org/10.1016/j.ahj.2010.11.010Get rights and content

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.

Section snippets

Patient population

We prospectively evaluated the effect of platelet reactivity after clopidogrel treatment on the risk of ST in 1,608 consecutive patients undergoing PCI—predominantly with drug-eluting stent (DES) implantation—after pretreatment with 600 mg clopidogrel at the Deutsches Herzzentrum and first Medizinische Klinik, Klinikum rechts der Isar, both in Munich.8 Patients were included irrespective of their clinical presentation unless they had a contraindication to aspirin or clopidogrel or had been

Results

In our population consisting of 1,608 patients, 232 patients (14.4%) were on CCBs on admission. Baseline clinical characteristics of the study population are shown in Table I. Patients with CCBs were significantly older, more likely to be women, and had more often arterial hypertension, more diabetes, and a higher body mass index compared to patients without CCB treatment. Among CCB-treated patients, the prescribed CCB was amlodipine in 171 patients (73.7%), lercanidipine in 23 patients (9.9%),

Discussion

The main finding of this study is that in our population, concomitant CCB therapy does not alter clopidogrel-mediated platelet aggregation measured by MEA and that there was no statistical difference in the incidence of death or ST and other ischemic events.

To the best of our knowledge, this is the largest patient population that was evaluated in this context. In this study, most patients received amlodipine, which showed no attenuation of platelet aggregation. Patients treated with verapamil,

Conclusion

In this large retrospective post hoc analysis, we found no evidence that concomitant CCB therapy does alter clopidogrel-mediated platelet aggregation and that there was no measurable impact on the incidence of ST, mortality, and other ischemic events. Further studies are needed to evaluate the pharmacodynamic and clinical impact of concomitant CCB treatment in patients with clopidogrel therapy after coronary stenting.

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