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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| non-amlodipine | Active Comparator | For patient with suboptimal angina control: anti-anginal agent excluding calcium channel blocker |
|
| non - amlodipine | Active Comparator | For patient with suboptimal BP control: anti-hypertensive agent excluding calcium channel blocker |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Amlodipine | Drug | For patient with suboptimal angina control: oral 2.5-10mg daily |
|
| Measure | Description | Time Frame |
|---|---|---|
| Platelet reactivity unit | Platelet reactivity unit as measured by VerifyNow system | baseline and 4 th week |
| Measure | Description | Time Frame |
|---|---|---|
| Percentage inhibition of platelet activity | Percentage inhibition of platelet activity measured by VerifyNow system | baseline and 4th week |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Andrew YW Li, MB | Ruttonjee Hospital | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Ruttonjee Hospital | Hong Kong SAR | China |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 23118347 | Derived | Li AY, Ng FH, Chan FK, Tunggal P, Chan K, Lau YK. Effect of amlodipine on platelet inhibition by clopidogrel in patients with ischaemic heart disease: a randomised, controlled trial. Heart. 2013 Apr;99(7):468-73. doi: 10.1136/heartjnl-2012-302801. Epub 2012 Oct 31. |
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| ID | Term |
|---|---|
| D017202 | Myocardial Ischemia |
| ID | Term |
|---|---|
| D006331 | Heart Diseases |
| D002318 | Cardiovascular Diseases |
| D014652 | Vascular Diseases |
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| ID | Term |
|---|---|
| D017311 | Amlodipine |
| ID | Term |
|---|---|
| D004095 | Dihydropyridines |
| D011725 | Pyridines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
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| Amlodipine | Drug | For patient with suboptimal BP control: 2.5-10mg daily po |
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