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

Thromb Haemost. 2010 May;103(5):920-5. doi: 10.1160/TH09-08-0516. Epub 2010 Mar 29.


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 muM adenosine diphospate (ADP) and clopidogrel poor-response (defined as > 70% platelet aggregation to 20 muM 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 amlodipine 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / antagonists & inhibitors
  • Aged
  • Amlodipine / pharmacology*
  • Angioplasty*
  • Blood Platelets / drug effects*
  • Blood Platelets / metabolism
  • Blood Platelets / pathology
  • Calcium Channel Blockers / pharmacology
  • Clopidogrel
  • Coronary Restenosis / prevention & control
  • Coronary Thrombosis / drug therapy
  • Coronary Thrombosis / etiology*
  • Drug Interactions
  • Drug Therapy, Combination
  • Female
  • Humans
  • Male
  • Middle Aged
  • Platelet Activation / drug effects
  • Platelet Aggregation Inhibitors / pharmacology*
  • Platelet Aggregation Inhibitors / therapeutic use
  • Postoperative Complications / prevention & control
  • Prospective Studies
  • Ticlopidine / analogs & derivatives
  • Ticlopidine / pharmacology
  • Ticlopidine / therapeutic use


  • ATP Binding Cassette Transporter, Subfamily B, Member 1
  • Calcium Channel Blockers
  • Platelet Aggregation Inhibitors
  • Amlodipine
  • Clopidogrel
  • Ticlopidine