Omeprazole and atorvastatin reduces the ability of clopidogrel to inhibit platelet aggregation in patients undergoing percutaneous coronary intervention in a tertiary health care system: A prospective drug-drug interaction study

Background: Clopidogrel, a prodrug is found to be less effective in inhibiting the platelet aggregation when administered along with PPI's in patients undergoing cardiac stent, ST segment elevated Myocardial infarction (STEMI) followed by percutaneous coronary intervention (PCI). Clopidogrel binds to CYP2C19, a hepatic enzyme to get converted to its active metabolite in order to achieve desired pharmacological activity. The cytochrome P450 3A4 which is partially involved in the metabolism of clopidogrel also metabolizes statins, mainly atorvastatin to the greater extent. Methodology: In the current study patients on PPI's with dual antiplatelet therapy and patients on PPI's and statins with dual antiplatelet therapy are considered to understand the potential drug-drug interactions (pDDI) among the South Asian population. Platelet aggregation was measured in 61 patients undergoing coronary artery stent implantation treated with clopidogrel and aspirin along with PPI's and statins. Results: It was observed that omeprazole and atorvastatin, but not pantoprazole and rosuvastatin, inhibited the antiplatelet activity of clopidogrel. The percent platelet aggregation was 72 +/- 6 (p = 0.001) and 43 +/- 23 (p = 0.027) in the presence of clopidogrel with omeprazole and pantoprazole respectively. Aggregation was found to be 91 +/- 4 (p = 0.001) and 12 +/- 23 (p = 0.031) in the presence of clopidogrel with atorvastatin and rosuvastatin respectively. Conclusion: A prominent drug-drug interaction was observed with patients on dual antiplatelet therapy along with omeprazole and atorvastatin. (C) 2016 Published by Elsevier Ireland Ltd. This is an open access article under the CC BY-NC-ND license.