Impact of concomitant use of proton-pump inhibitors and thienopyridine derivatives on the antiplatelet effects.

Abstract

BACKGROUND:

Although there has been an intense debate whether concomitant use of proton-pump inhibitors (PPIs) attenuates the antiplatelet effects of thienopyridine derivatives, the drug-drug interaction remains unclear in Japanese patients with coronary artery disease.

METHODS AND RESULTS:

Platelet function test was performed in 461 patients who were scheduled for or had undergone stent implantation, treated with 100mg/day of aspirin and a thienopyridine (200mg/day of ticlopidine or 75 mg/day of clopidogrel) for at least 14 days. Adenosine diphosphate-induced platelet aggregation was evaluated with screen filtration pressure method, and the upper quartile of high platelet reactivity was defined as high on-treatment platelet reactivity (HPR). PPI use was at physician's discretion. Patients taking a thienopyridine plus a PPI (n=166) were older and had a higher incidence of acute coronary syndromes on admission compared with patients taking a thienopyridine without a PPI (n=295). The rate of HPR was higher in patients taking a thienopyridine plus a PPI than in patients taking a thienopyridine without a PPI (31% vs 21%, p=0.01). On multivariate logistic regression analysis, independent predictors of HPR were concomitant PPI use [odds ratio (OR): 1.66, 95% confidence interval (CI): 1.03-2.68], diabetes mellitus (OR: 1.76, CI: 1.11-2.81), and calcium channel blockers use (OR: 1.93, CI: 1.18-3.18). However, there was no significant difference in the rate of extremely high platelet reactivity [58 patients (12.5%) with PATI<4.0 μM] between patients treated with a thienopyridine plus a PPI and those without a PPI (14% vs 11%, NS).

CONCLUSION:

HPR was frequently observed in Japanese patients treated with thienopyridines plus PPIs compared to those without PPIs. Further prospective studies are needed to estimate the risk of adverse cardiovascular events associated with concomitant use of PPIs and thienopyridines.

• Authors: Kengo Tsukahara, Kazuo Kimura, Satoshi Morita, Toshiaki Ebina, Masami Kosuge, Kiyoshi Hibi, Noriaki Iwahashi, Mitsuaki Endo, Nobuhiko Maejima, Teruyasu Sugano, Satoshi Umemura
• Journal: Journal of cardiology (J Cardiol) Vol. 57 Issue 3 Pg. 275-82 (May 2011) ISSN: 1876-4738 [Electronic] Netherlands
• PMID: 21371863 (Publication Type: Comparative Study, Journal Article)
• Copyright: Copyright © 2011 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.

Chemical References

• Platelet Aggregation Inhibitors
• Proton Pump Inhibitors
• Thienopyridines
• Clopidogrel
• Ticlopidine

Topics

• Acute Coronary Syndrome (drug therapy)
• Aged
• Clopidogrel
• Coronary Disease (drug therapy)
• Drug Interactions
• Female
• Humans
• Male
• Platelet Aggregation (drug effects)
• Platelet Aggregation Inhibitors (administration & dosage, pharmacology)
• Proton Pump Inhibitors (administration & dosage)
• Stents
• Thienopyridines (administration & dosage, pharmacology)
• Ticlopidine (administration & dosage, analogs & derivatives, pharmacology)