Pantoprazole Does Not Influence the Antiplatelet Effect of Clopidogrel-A Whole Blood Aggregometry Study After Coronary Stenting

Abstract

Recent attention has been drawn to a potential drug-drug interaction observed between clopidogrel and proton pump inhibitors (PPIs). However, this potential interaction may not be a class effect of PPIs. We investigated if pantoprazole, which has a different metabolism than omeprazole, diminishes the effectiveness of clopidogrel. Our study included 336 patients (mean age 64.6 years; 106 women) 48 hours after percutaneous coronary stent implantation with a loading dose of 600 mg clopidogrel hydrogensulfate and 500 mg aspirin, followed by 75 mg clopidogrel and 100 mg aspirin daily. Whereas 188 patients (59 women) were not given any PPI comedication, 122 patients received pantoprazole and 26 either omeprazole or esomeprazole. The platelet aggregation followed by impedance aggregometry (in Ohm) was induced by 5 mmol/L adenosine diphosphate. The percentage of clopidogrel low-response (CLR) was similar between the non-PPI group [2.75 Ohm (confidence interval, CI: 2.25-3.26); 21.9% CLR] and the pantoprazole group [2.33 Ohm (CI: 1.79-2.87); 16.4% CLR] but higher in patients treated with omeprazole/esomeprazole (3.00 Ohm (CI: 1.49-4.51); 30.8% CLR). Multivariate regression analysis reveals that the risk of CLR in the pantoprazole comedication group was not increased compared with the group without any PPI [odds ratio 0.59 (CI: 0.31-1.13) 0.11]. Our data suggest that pantoprazole does not diminish the antiplatelet effectiveness of clopidogrel early after coronary stenting. Therefore, the use of pantoprazole seems preferable in patients treated with clopidogrel when a concomitant medication with a PPI is indicated.

Clopidogrel–Drug Interactions

“…Sibbing et al (36) demonstrated less platelet inhibition and more nonresponders in patients taking omeprazole compared with non-PPI users or those given esomeprazole or pantoprazole. Neubauer et al (37) also found more clopidogrel nonresponders with omeprazole, but no interaction with pantoprazole. Staggering the administration times of clopidogrel and omeprazole does not decrease the interaction (38).…”

“…In summary, omeprazole has consistently been shown to attenuate clopidogrel responsiveness (34)(35)(36)(37)(38)43), whereas no or limited interaction has been shown with pantoprazole (35)(36)(37)41,43) and other PPIs.…”

Pharmacodynamic Evaluation of Pantoprazole Therapy on Clopidogrel Effects

“…15,16,23,24 However, at difference with prior investigations, our study also investigated whether concomitant versus staggered treatment could have an impact on the pharmacodynamic findings. This is noteworthy because it has been suggested that staggering treatment may be a modality to overcome the PPI-clopidogrel drug interaction.…”

Novel Antiplatelet Therapies

“…Specifically, omeprazole, metabolized mostly via CYP 2C19, is associated with decreased platelet inhibition and a higher clopidogrel "nonresponder" rate [24][25][26]. However, several studies have shown lack of such association with other PPIs, such as pantoprazole or esomeprazole [27,28]. Unfortunately, the only randomized clinical trial, the Clopidogrel and the Optimization of Gastrointestinal Events Trial (COGENT), was terminated prior to its completion [29].…”