Impact of Cigarette Smoking on P2Y12 Receptor Binding Activity Before and After Clopidogrel Therapy in Patients with Coronary Artery Disease

Smoking enhances the P2Y(12) receptor inhibitory effects of clopidogrel. Nicotine increases P2Y(12) receptor expression in platelet lysates from healthy volunteers. However, the impact of cigarette smoking on platelet P2Y(12) receptor binding in clopidogrel-treated patients with coronary artery disease (CAD) is unknown. Clopidogrel-na < ve patients with stable CAD (n = 20) were enrolled and stratified according to smoking status. P2Y(12) receptor binding activity was determined by radioligand receptor binding prior and 24 h after a 600-mg loading dose of clopidogrel. Baseline P2Y(12) receptor binding was 1.8-fold higher in smokers compared with nonsmokers. After a 600-mg loading dose of clopidogrel, smokers showed a 6.4-fold reduction in P2Y(12) receptor binding indicative of marked clopidogrel-mediated blockade, while there were minimal changes among nonsmokers. Among patients with stable CAD, smokers have more P2Y(12) receptor binding than nonsmokers and have a higher degree of clopidogrel-mediated platelet inhibition.