Clopidogrel–Drug Interactions

Perspective:

The following are 10 points to remember about this state-of-the-art paper on clopidogrel–drug interactions:

1. 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.

2. Physical and genetic factors that induce, inhibit, or compete for CYP activity can modulate biotransformation of clopidogrel to its active metabolite and result in interindividual variability of clopidogrel responsiveness.

3. Importantly, clopidogrel–atorvastatin and clopidogrel–omeprazole drug interactions have been described that limit the ability of clopidogrel to inhibit platelet activation and aggregation processes.

4. The clinical implications of these pharmacodynamic interactions have raised concern because many of these drugs are concomitantly administered to patients with coronary artery disease.

5. There are many pharmacodynamic clopidogrel–drug interactions, but to date, there is no consistent evidence that clopidogrel–drug interactions impact adverse cardiovascular events.

6. A major obstacle to finding a clinical clopidogrel–drug interaction is assuring patient compliance with coadministration of both medications during the study period. Measuring medication use at one point in time does not assure continued use of both medications.

7. There are many other confounding variables that have contributed to the discordant results regarding potential clopidogrel–drug interactions including dose effect, class effect, time effect, clopidogrel response variability, and offsetting clinical effects.

8. Because the benefit of dual antiplatelet therapy is well established and the existing clinical data on clopidogrel–drug interactions are inconclusive, clinicians should concentrate on initiating proper statin therapy in patients with coronary artery disease and prescribing proton pump inhibitors for patients at increased risk for gastroduodenal bleeding.

9. Furthermore, 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.

10. 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 gastroprotective agents that do not interfere with clopidogrel metabolism.

Clinical Topics: Dyslipidemia, Lipid Metabolism, Nonstatins, Novel Agents, Statins

Keywords: Cytochrome P-450 Enzyme System, Coronary Artery Disease, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Blood Platelets, Heptanoic Acids, Proton Pump Inhibitors, Drug Interactions, Pyrroles, Omeprazole, Platelet Activation, Biotransformation, Patient Compliance


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