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Calcium-channel blockers decrease clopidogrel-mediated platelet inhibition
  1. Thomas Gremmel1,
  2. Sabine Steiner1,
  3. Daniela Seidinger1,
  4. Renate Koppensteiner1,
  5. Simon Panzer2,
  6. Christoph W Kopp1
  1. 1Division of Angiology, Department of Internal Medicine II, Medical University of Vienna, Vienna, Austria
  2. 2Division of Blood Group Serology, Department of Blood Group Serology and Transfusion Medicine, Medical University of Vienna, Vienna, Austria
  1. Correspondence to Dr Thomas Gremmel, Division of Angiology, Department of Internal Medicine II, Medical University of Vienna, Waehringer Guertel 18-20, 1090 Vienna, Austria; thomas.gremmel{at}meduniwien.ac.at

Abstract

Background The extent of clopidogrel-mediated platelet inhibition varies considerably from one person to the next. Numerous studies have shown that low responders have significantly more adverse events after coronary stenting than patients who respond well to antithrombotic treatment with clopidogrel. Dihydropyridine calcium-channel blockers (CCBs) inhibit the cytochrome P450 3A4 enzyme, which metabolises clopidogrel to its active form.

Objective To investigate the influence of CCBs on clopidogrel-mediated platelet inhibition.

Methods Adenosine-5-diphosphate (ADP)-inducible platelet reactivity was assessed by light transmission aggregometry (LTA) and the VerifyNow P2Y12 assay in 162 patients after percutaneous intervention with stent implantation. Results in the fourth quartiles of both assays were considered as high on-treatment residual ADP-inducible platelet reactivity.

Results Patients with concomitant CCB therapy showed a significantly higher on-treatment platelet reactivity than patients without CCB medication (p=0.001 for both assays). Further, high on-treatment residual ADP-inducible platelet reactivity was significantly more common among patients currently taking CCBs (p=0.001 for LTA and p=0.004 for the VerifyNow P2Y12 assay). A multivariate regression analysis confirmed CCB therapy as an independent predictor of reduced clopidogrel-mediated platelet inhibition (p=0.006 for LTA and p=0.004 for the VerifyNow P2Y12 assay).

Conclusion CCBs decrease clopidogrel-mediated platelet inhibition in patients undergoing angioplasty and stenting for cardiovascular disease.

  • Clopidogrel
  • calcium-channel blockers
  • platelet function testing
  • coronary stenting
  • non-coronary intervention
  • antiplatelet treatment

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Footnotes

  • See Editorial, page 179

  • Competing interests None.

  • Ethics approval This study was conducted with the approval of the ethics committee of the Medical University of Vienna.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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