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

Overview

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.

Full Title of Study: “Effect of Amlodipine on Platelet Inhibition by Clopidogrel in Patients With Ischemic Heart Disease- a Prospective Randomized Controlled Trial”

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: Randomized
    • Intervention Model: Parallel Assignment
    • Primary Purpose: Treatment
    • Masking: None (Open Label)
  • Study Primary Completion Date: April 2011

Detailed Description

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.

Interventions

  • Drug: Amlodipine
    • For patient with suboptimal angina control: oral 2.5-10mg daily
  • Drug: Amlodipine
    • For patient with suboptimal BP control: 2.5-10mg daily po

Arms, Groups and Cohorts

  • Active Comparator: non-amlodipine
    • For patient with suboptimal angina control: anti-anginal agent excluding calcium channel blocker
  • Active Comparator: non – amlodipine
    • For patient with suboptimal BP control: anti-hypertensive agent excluding calcium channel blocker

Clinical Trial Outcome Measures

Primary Measures

  • Platelet reactivity unit
    • Time Frame: baseline and 4 th week
    • Platelet reactivity unit as measured by VerifyNow system

Secondary Measures

  • Percentage inhibition of platelet activity
    • Time Frame: baseline and 4th week
    • Percentage inhibition of platelet activity measured by VerifyNow system

Participating in This Clinical Trial

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.

Gender Eligibility: All

Minimum Age: 18 Years

Maximum Age: N/A

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • Ruttonjee Hospital
  • Provider of Information About this Clinical Study
    • Sponsor
  • Overall Official(s)
    • Andrew YW Li, MB, Principal Investigator, Ruttonjee Hospital

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