• Clopidogrel
• platelets
• antiplatelet treatment
• calcium-channel blockers

Antiplatelet treatment has a pivotal role in modern management of coronary artery disease, and use of clopidogrel has facilitated the emergence of intravascular stenting as common cardiological practice. However, clopidogrel responsiveness is heterogeneous within the population, with a sizeable proportion seemingly unresponsive to its antiplatelet effects and at higher risk of cardiovascular events as a result.1 2

Clopidogrel is a pro-drug that is metabolised by cytochrome P450 (CYP) enzymes (including the 3A4 and 2C19 isoforms) to an active thiol metabolite that antagonises the platelet adenosine diphosphate (ADP) receptor P2Y12. Carriers of loss-of-function polymorphisms in the genes coding for CYP2C19 have lower levels of the active metabolite, reduced clopidogrel-induced platelet inhibition and are at increased risk of cardiovascular events and stent thrombosis, compared with non-carriers.3 Drugs that inhibit hepatic CYP450 enzymes might be expected to reduce clopidogrel activation in a similar way with similar adverse clinical results. Calcium-channel blockers (CCBs) are frequently used in patients with cardiovascular disease; both non-dihydropyridine and dihydropyridine CCBs are metabolised by, and inhibit, the 3A4 isoform of CYP450 and have potential for interaction with other drugs in this way.4

In this issue of Heart, Gremmel and colleagues describe a prospective observational study of the influence of …