Key result
Clopidogrel co-administration with statins or proton pump inhibitors lacks consistent evidence of increasing adverse cardiovascular events, and these beneficial therapies should not be withheld.
Why the study?
The clinical implications of pharmacodynamic drug-drug interactions with clopidogrel in patients with coronary artery disease remain uncertain due to lack of consistent evidence on adverse cardiovascular events.
Does coadministration of CYP-interacting drugs (like statins and proton pump inhibitors) with clopidogrel impact adverse cardiovascular events in patients with coronary artery disease?
Does coadministration of CYP-interacting drugs (like statins and proton pump inhibitors) with clopidogrel impact adverse cardiovascular events in patients with coronary artery disease?
Statins and proton pump inhibitors should not be withheld from patients with appropriate indications due to theoretical concerns over clopidogrel-drug interactions, as no consistent evidence shows this impacts adverse cardiovascular events.
Multidrug therapy increases the risk for drug-drug interactions. Clopidogrel, a prodrug, requires hepatic cytochrome P450 (CYP) metabolic activation to produce the active metabolite that inhibits the platelet P2Y₁₂ adenosine diphosphate (ADP) receptor, decreasing platelet activation and aggregation processes. Atorvastatin, omeprazole, and several other drugs have been shown in pharmacodynamic studies to competitively inhibit CYP activation of clopidogrel, reducing clopidogrel responsiveness. Conversely, other agents increase clopidogrel responsiveness by inducing CYP activity. The clinical implications of these pharmacodynamic interactions have raised concern because many of these drugs are coadministered to patients with coronary artery disease. There are multiple challenges in proving that a pharmacodynamic drug-drug interaction is clinically significant. To date, there is no consistent evidence that clopidogrel-drug interactions impact adverse cardiovascular events. Statins and proton pump inhibitors have been shown to decrease adverse clinical event rates and should not be withheld from patients with appropriate indications for therapy because of concern about potential clopidogrel-drug interactions. Clinicians concerned about clopidogrel-drug interactions have the option of prescribing either an alternative platelet P2Y₁₂ receptor inhibitor without known drug interactions, or statin and gastro-protective agents that do not interfere with clopidogrel metabolism.
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Bates et al. (2011) conducted a review in Coronary artery disease. Clopidogrel co-administration with statins or proton pump inhibitors was evaluated on Adverse cardiovascular events. Clopidogrel co-administration with statins or proton pump inhibitors lacks consistent evidence of increasing adverse cardiovascular events, and these beneficial therapies should not be withheld.
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