Gut Liver.  2017 Jul;11(4):504-511. 10.5009/gnl16352.

Pantoprazole Does Not Reduce the Antiplatelet Effect of Clopidogrel: A Randomized Controlled Trial in Korea

Affiliations
  • 1Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea. nayoungkim49@empas.com
  • 2Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea.
  • 3Department of Clinical Pharmacology and Therapeutics, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea.

Abstract

BACKGROUND/AIMS
Concerns that proton pump inhibitors (PPIs) diminish the efficacy of clopidogrel could hamper the appropriate prescription of PPIs. We evaluated the influence of pantoprazole on the antiplatelet effect of clopidogrel compared with ranitidine, which is regarded as safe, after stratification of the population according to the presence of a cytochrome (CYP) 2C19 polymorphism in Korea.
METHODS
Forty patients who underwent dual antiplatelet therapy were randomized to receive pantoprazole (n=20) or ranitidine (n=20). Platelet aggregation was evaluated by impedance aggregometry at baseline (D0) and 8 days after acid-lowering treatments (D9). CYP2C19 was genotyped by polymerase chain reaction restriction fragment length polymorphism.
RESULTS
After co-treatment, the percentage of clopidogrel low-response was 11.1% (2/18) in the pantoprazole group and 10.5% (2/19) in the ranitidine group (p=0.954). The impedance values with adenosine diphosphate stimulus after acid-lowering treatments did not significantly differ between the two groups. In a multiple regression analysis, only ST-elevation myocardial infarction was marginally associated with a reduced antiplatelet effect (odds ratio, 12.07; 95% confidence interval, 0.84 to 173.78). However, pantoprazole use did not affect the antiplatelet effect after correction for the CYP2C19 polymorphism.
CONCLUSIONS
This study showed that pantoprazole does not increase platelet aggregation in patients receiving dual antiplatelet therapy (ClinicalTrials.gov number: NCT02733640).

Keyword

Clopidogrel low response; Drug interactions; Polymorphism; Proton pump inhibitors

MeSH Terms

2-Pyridinylmethylsulfinylbenzimidazoles/*pharmacology
Acute Coronary Syndrome/*drug therapy/genetics
Aged
Cytochrome P-450 CYP2C19/analysis
Drug Interactions
Drug Therapy, Combination
Female
Humans
Male
Middle Aged
Platelet Aggregation/*drug effects
Platelet Aggregation Inhibitors/*pharmacology
Platelet Function Tests
Ranitidine/pharmacology
Republic of Korea
Single-Blind Method
Ticlopidine/*analogs & derivatives/pharmacology
2-Pyridinylmethylsulfinylbenzimidazoles
Platelet Aggregation Inhibitors
Ranitidine
Cytochrome P-450 CYP2C19
Ticlopidine
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