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

Abstract

Background/AimsConcerns 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.MethodsForty 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.ResultsAfter 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.ConclusionsThis study showed that pantoprazole does not increase platelet aggregation in patients receiving dual antiplatelet therapy (ClinicalTrials.gov number: NCT02733640).

Prevention of Anthracycline-Induced Cardiotoxicity: The Good and Bad of Current and Alternative Therapies

“…In addition, CYP2C19 inhibition in a clinical study involving readmitted patients with myocardial infarction, demonstrated an increased risk of reinfarction (111). In contrast, another clinical study, of patients receiving dual antiplatelet therapy, revealed no significant effect on platelet aggregation following CYP2C19 inhibition (112). In essence these variations in the clinical outcome of CYP2C19 activity highlight the intricacy of pharmacokinetics in treatment and disease response.…”

Prescription of proton pump inhibitors in older adults with complex polytherapy

“…Consequently, the risk of thrombosis would be increased for patients on polytherapy as clopidogrel would not be activated. Notably, pantoprazole did not appear to interact with clopidogrel whereas all the other PPIs did; in fact, pantoprazole is known to weakly inhibit CYP2C19 22 23. The non-interaction of pantoprazole could be a potential solution in cases where an antiplatelet agent and a PPI are strictly needed and could be explained by its slightly different mechanism of action.…”

Effects of different CYP2C19 genotypes on prognosis of patients complicated with atrial fibrillation taking clopidogrel after PCI

“…CYP2C19-2 and CYP2C19-3 are PM subtypes of CYP2C19 ( 14 ), which are mainly expressed in Asian populations ( 15 ) with higher mutation rates ( 16 ); thus, the incidence rate of severe cardiovascular complications is increased significantly in PM subjects ( 17 ). The long-term application of clopidogrel in patients complicated with atrial fibrillation after PCI should be paid attention to ( 18 ); the anti-platelet therapy regimen should be adjusted in time ( 19 ) to avoid stent thrombosis-induced complications ( 20 ).…”