Effect of Amlodipine on Anti-platelet Drug Effect in Patients With Coronary Artery Disease
Clopidogrel can reduce risk of cardiovascular disease by inhibiting platelet aggregation. It is metabolized to an active drug by a liver enzyme. Its efficacy may be measured by blood sampling for platelet activity, analyzed by VerifyNow device. Calcium Channel blocker (CCB) is also commonly used for blood pressure and anginal control in these patients. Dihydropyridine group of calcium channel blocker (e.g. amlodipine) inhibits this enzyme. There are observational studies reporting dihydropyridine CCB reducing clopidogrel effect, but the clinical implication is unclear.
This study test the hypothesis that there is no significant effect of dihydropyridines CCB on clopidogrel response compared with control. After giving consent, patients with suboptimal blood pressure or anginal control will be randomized to receive either dihydropyridine CCB or non-CCB as placebo. These patient will be follow-up in 1 month.
|Study Design:||Allocation: Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Effect of Amlodipine on Platelet Inhibition by Clopidogrel in Patients With Ischemic Heart Disease- a Prospective Randomized Controlled Trial|
- Platelet reactivity unit [ Time Frame: baseline and 4 th week ] [ Designated as safety issue: No ]Platelet reactivity unit as measured by VerifyNow system
- Percentage inhibition of platelet activity [ Time Frame: baseline and 4th week ] [ Designated as safety issue: No ]Percentage inhibition of platelet activity measured by VerifyNow system
|Study Start Date:||July 2010|
|Study Completion Date:||April 2011|
|Primary Completion Date:||April 2011 (Final data collection date for primary outcome measure)|
Active Comparator: non-amlodipine
For patient with suboptimal angina control: anti-anginal agent excluding calcium channel blocker
For patient with suboptimal angina control: oral 2.5-10mg daily
Other Name: Norvasc
Active Comparator: non - amlodipine
For patient with suboptimal BP control: anti-hypertensive agent excluding calcium channel blocker
For patient with suboptimal BP control: 2.5-10mg daily po
Other Name: Norvasc
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01203696
|Hong Kong SAR, China|
|Principal Investigator:||Andrew YW Li, MB||Ruttonjee Hospital|