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

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.