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

Yoon Jin Choi, Nayoung Kim, In-Jin Jang, Joo-Youn Cho, Ryoung Hee Nam, Ji Hyun Park, Hyun Jin Jo, Hyuk Yoon, Cheol Min Shin, Young Soo Park, Dong Ho Lee, Hyun Chae Jung, Yoon Jin Choi, Nayoung Kim, In-Jin Jang, Joo-Youn Cho, Ryoung Hee Nam, Ji Hyun Park, Hyun Jin Jo, Hyuk Yoon, Cheol Min Shin, Young Soo Park, Dong Ho Lee, Hyun Chae Jung

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).

Keywords: Clopidogrel low response; Drug interactions; Polymorphism; Proton pump inhibitors.

Conflict of interest statement

CONFLICTS OF INTEREST

No potential conflict of interest relevant to this article was reported.

Figures

Fig. 1
Fig. 1
CONSORT study flow chart.
Fig. 2
Fig. 2
Antiplatelet effect of clopidogrel on days 0 and 9 in patients with concomitant use of ranitidine (A) and pantoprazole (B) during follow-up. There were no significant differences between the groups (by Wilcoxon signed-rank test).

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