Thromb Haemost 2010; 103(05): 920-925
DOI: 10.1160/TH09-08-0516
Theme Issue Article
Schattauer GmbH

The use of amlodipine, but not of P-glycoprotein inhibiting calcium channel blockers is associated with clopidogrel poor-response

Ankie M. Harmsze
1   Department of Clinical Pharmacy, St. Antonius Hospital, Nieuwegein, The Netherlands
2   Division of Pharmacoepidemiology and Pharmacotherapy, Utrecht Institute for Pharmaceutical Sciences (UIPS), Utrecht University, Utrecht, The Netherlands
,
Karen Robijns
1   Department of Clinical Pharmacy, St. Antonius Hospital, Nieuwegein, The Netherlands
,
Jochem W. van Werkum
3   Department of Cardiology, St. Antonius Hospital, Nieuwegein, The Netherlands
,
Nicoline J. Breet
3   Department of Cardiology, St. Antonius Hospital, Nieuwegein, The Netherlands
,
Christian M. Hackeng
4   Department of Clinical Chemistry, St. Antonius Hospital, Nieuwegein, The Netherlands
,
Jurrien M. ten Berg
3   Department of Cardiology, St. Antonius Hospital, Nieuwegein, The Netherlands
,
Hendrik J. T. Ruven
4   Department of Clinical Chemistry, St. Antonius Hospital, Nieuwegein, The Netherlands
,
Olaf H. Klungel
2   Division of Pharmacoepidemiology and Pharmacotherapy, Utrecht Institute for Pharmaceutical Sciences (UIPS), Utrecht University, Utrecht, The Netherlands
,
Anthonius de Boer
2   Division of Pharmacoepidemiology and Pharmacotherapy, Utrecht Institute for Pharmaceutical Sciences (UIPS), Utrecht University, Utrecht, The Netherlands
,
Vera H. M. Deneer
1   Department of Clinical Pharmacy, St. Antonius Hospital, Nieuwegein, The Netherlands
› Institutsangaben
Financial support: The division of Pharmacoepidemiology & Pharmacotherapy employing authors AMH, OHK and AB has received unrestricted funding for pharmacoepidemiological research from GlaxoSmithKline, Novo Nordisk, the private-public funded Top Institute Pharma (www.tipharma.nl, includes co-funding from universities, government, and industry), the Dutch Medicines Evaluation Board, and the Dutch Ministry of Health.
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Publikationsverlauf

Received: 01. August 2009

Accepted after major revision: 03. Februar 2010

Publikationsdatum:
22. November 2017 (online)

Summary

Clopidogrel is a prodrug that has to be converted in vivo to its active metabolite by cytochrome (CYP)P450 iso-enzymes. As calcium channel blockers (CCBs) are inhibitors of CYP3A4, concomitant use of these drugs might play a role in the wide inter-individual variability in the response to clopidogrel. However, some CCBs also have strong inhibitory effects on the drug transporter P-glycoprotein (Pgp), which mediates clopidogrel‘s intestinal absorption. It was the aim of this study to evaluate the effect of co-administration of Pgp-inhibiting and non-Pgp-inhibiting CCBs on on-clopidogrel platelet reactivity in patients on dual antiplatelet therapy undergoing elective percutaneous coronary intervention (PCI). In a total of 623 consecutive patients undergoing elective PCI treated with clopidogrel and aspirin, platelet reactivity to 5 and 20 μM adenosine diphospate (ADP) and clopidogrel poor-response (defined as > 70% platelet aggregation to 20 μM ADP) were evaluated by light transmittance aggregometry. A total of 222 patients (35.6%) were on CCB treatment, of which 98 used Pgp-inhibiting CCBs (verapamil, nifedipine, diltiazem, barnidipine) and 124 patients used the non-Pgp-inhibiting CCB amlodipine. Adjusted mean ADP-induced on-clopidogrel platelet reactivity was significantly higher in both users of Pgp-inhibiting CCBs and amlodipine as compared to CCB non-users (all p<0.05). However, only the use of amlodipine was significantly associated with a 2.3-fold increased risk of clopidogrel poor-response. This study demonstrates that concomitant use of Pgp-inhibiting CCBs and amlodipine increases on-clopidogrel platelet reactivity. Only amlodi-pine was associated with clopidogrel poor-response. The drug-drug interaction between clopidogrel and amlodipine might be more clinically relevant as compared to P-glycoprotein-inhibiting CCBs.

 
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