Influence of Varenicline on the Antiplatelet Action of Clopidogrel

Study Overview
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Brief Summary
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The purpose of this study is to investigate the effects of steady-state varenicline on the antiplatelet action of clopidogrel in patients with coronary artery disease.

Detailed Description
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Smoking is a major risk factor for cardiovascular disease (CVD). Compared with nonsmokers, smokers are approximately twice as likely to develop CVD, and three times more likely to die from it. This increased risk is due to the deleterious effects of smoking on endothelial function and blood coagulation, and the development of coronary atherosclerotic plaques. A research showed that continued smoking after successful percutaneous coronary intervention(PCI) is associated with an increased risk of restenosis. However, smoking cessation can make a 36% reduction in crude relative risk (RR) of mortality for patients with CVD. Hence current management guidelines now advocate smoking cessation, in addition to controlling hypertension and dyslipidemia, as part of an overall cardiovascular risk reduction strategy. Varenicline is a novel selective nicotinic acetylcholine receptor partial agonist that has been approved in over 70 countries worldwide as an aid to smoking cessation. Clopidogrel is widely used by patients with coronary artery disease undergoing PCI. The relationship between smoking and cardiovascular disease increases the prospect of patients receiving smoking cessation therapy and Clopidogrel concomitantly in clinical practice. Plasma protein binding of Varenicline is low(≤20%) and independent of age or renal function. The major route of clearance for varenicline is renal excretion. Clopidogrel, a prodrug, is metabolized by 2 consecutive cytochrome P450-dependent steps to its active metabolite, which binds irreversibly to the platelet P2Y12 receptor. The likelihood of a clinically relevant drug-drug interaction between varenicline and Clopidogrel was considered to be low; nevertheless, the possibility of an interaction between these 2 drugs is lack of clinical evidences. Hence, our hypothesis is that varenicline may have no influence on the antiplatelet action of clopidogrel.

Official Title
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Influence of Varenicline on the Antiplatelet Action of Clopidogrel : the Randomized, Open-label VACL (Varenicline Clopidogrel) Study

Conditions
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Coronary Artery Disease

Intervention / Treatment
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* Drug: Varenicline
* Behavioral: Counseling and psychosocial support


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: patients with coronary artery disease(CAD) undergoing PCI in hospital smoke 10 or more cigarettes per day fewer than 3 months of smoking abstinence in the past year motivation to stop smoking Exclusion Criteria: history of previous treatment with clopidogrel or varenicline thrombocytopenia(<150,000 platelets/ml) bleeding disorder liver disease gastrointestinal ulcer pregnancy cancer clinically significant allergic reactions mental disorders drug or alcohol abuse

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 79 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: varenicline<br>On 3 day after received clopidogrel 75mg/day, Varenicline group will be administered with varenicline 0.5mg Qd,after 3 days, 0.5mg Bid,after 7days,1mg Bid .And received counseling and psychosocial support. | Drug: Varenicline<br>* Varenicline will be administrated 0.5 mg Qd for 3 days,0.5 mg Bid for 4 days, and then 1 mg Bid for 14 days<br>* Other names: Champix;Behavioral: Counseling and psychosocial support<br>* Blank group will receive the same counseling and psychosocial support as varenicline group<br>* Other names: nonpharmacologic therapy;|
| Other: Blank<br>Blank group will be only administered with Counseling and psychosocial support,beside antiplatelet etc.conventional therapy for 14 days. | Behavioral: Counseling and psychosocial support<br>* Blank group will receive the same counseling and psychosocial support as varenicline group<br>* Other names: nonpharmacologic therapy;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The platelet reactivity index (PRI) values in the two groups | To compare PRI values at the 14-day-treatment period between the 2 groups. | 14 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Platelet aggregometry values in the two groups | To compare platelet aggregometry values at the 7-day,14-day-treatment period between the 2 groups. | 7days,14 days | 
| Urea nitrogen （BUN） and creatinine（Cr）values in the two groups | To compare BUN and Cr values at the 7-day,14-day-treatment period between the 2 groups. | 7days, 14 days | 
| Number of patients with adverse events and serious adverse events as a measure of safety in the two groups | To compare the number of patients with adverse events and serious adverse events at the 7-day,14-day-treatment period between the 2 groups | 7 days,14 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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coronary artery disease, varenicline, clopidogrel