Effect of Amlodipine on Anti-platelet Drug Effect in Patients With Coronary Artery Disease

Clopidogrel is a pro-drug, which requires hepatic transformation by the cytochrome P450 isoform 3A4 to generate the active metabolite. It inhibits adenosine-5-diphosphate (ADP)-induced platelet aggregation by irreversibly blocking the platelet P2Y12 receptor. However, response to clopidogrel shows wide individual variability, and patients with high on-treatment residual ADP-induced platelet reactivity are at an increased risk of adverse cardiovascular events. Previous study suggest co-administration of CCBs is associated with decreased platelet inhibition by clopidogrel, but these observational studies are confounded by patient's characteristics baseline difference such as proportion of hypertension and diabetes.

The objective of this randomized controlled study is to compare amlodipine with placebo on anti-platelet effect of clopidogrel.

Inclusion criteria

• ischemic heart disease patient, and
• given loading or maintenance dose of clopidogrel and in need of it for 1 or more month
• and in need of additional drug for optimal BP control (aim blood pressure <130/90) or angina control.

Exclusion criteria

• existing use of amlodipine
• thrombocytopenia
• end stage renal failure
• allergy to clopidogrel/ amlodipine
• pregnancy/ lactation
• strong inhibitor or inducer of cytochrome P450 3A4 enzyme within 7 days before start of the study.