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Calcium-channel blockers blunt clopidogrel action after stenting

22 January 2010

MedWire News: Calcium-channel blocker (CCB) therapy appears to interfere with clopidogrel-mediated platelet inhibition in patients undergoing angioplasty and stenting for cardiovascular disease (CVD), study results show.

Response to clopidogrel varies widely between individuals, and recent studies suggest that patients with high on-treatment residual ADP-inducible platelet reactivity are at an increased risk for adverse events after coronary stenting.

Dihydropyridine CCBs inhibit the cytochrome P450 3A4 enzyme, which metabolizes clopidogrel to its active form.

A recent study using the vasodilator-stimulated phosphoprotein (VASP) assay and multiple electrode aggregometry (MEA) found a reduction of the antiplatelet effect of clopidogrel in patients with concomitant CCB therapy.

But as these tests are relatively new, clinical outcome data are lacking for both assays.

In the present study the researchers assessed platelet reactivity by light transmission aggregometry (LTA) - which has been established as a “gold standard” for assessment of platelet function during antithrombotic therapy with clopidogrel, and results of which numerous studies have associated with adverse events after coronary stenting. They also used the VerifyNow P2Y12 assay, a fast point-of-care test, which has been shown to correlate strongly with LTA.

The study included 162 consecutive patients who underwent endovascular stent implantation with dual antiplatelet therapy, 53 (32.7%) of whom received concomitant CCB treatment.

Thomas Gremmel (Medical University of Vienna, Austria) and colleagues report that patients with CCB therapy showed significantly higher on-treatment platelet reactivity than patients without CCB medication on both assays (p=0.001).

Furthermore, high on-treatment residual ADP-inducible platelet reactivity was significantly more common among patients currently taking CCBs, at 41.5% versus 16.5% by LTA, respectively (p=0.001).

A multivariate regression analysis confirmed CCB treatment independently predicted reduced clopidogrel-mediated platelet inhibition.

“As these are in vitro data, large prospective clinical trials are warranted to clarify the impact of concomitant CCB therapy on the long-term outcome after angioplasty and stenting in patients treated with clopidogrel,” Gremmel et al conclude in the journal Heart.

MedWire (www.medwire-news.md) is an independent clinical news service provided by Current Medicine Group, a trading division of Springer Healthcare Limited. © Springer Healthcare Ltd; 2010

Heart 2009; Advance online publication