Varenicline-assisted smoking cessation decreases oxidative stress and restores endothelial function.

Smoking cessation decreases oxidative stress and restores vascular endothelial function. However, a recent meta-analysis suggests that the use of varenicline, a α4β2 nicotinic acetylcholine receptor partial agonist, increases the risk of cardiovascular events. This study was designed to determine the effect of varenicline-assisted smoking cessation on vascular endothelial function. Study subjects were 11 healthy Japanese males (mean age, 54.4 years) without evidence of cardiovascular disease who were eager to quit smoking. Each subject was treated with varenicline titrated up to 1.0 mg twice daily. We evaluated serum derivatives of reactive oxygen metabolites (d-ROMs) as a marker of oxidative stress, and flow-mediated dilation (FMD) of the brachial artery as a marker of vascular endothelial function. Both measurements were performed before and 3 months after completing smoking cessation. All subjects gained weight (average, 1.7 kg) after smoking cessation. However, there were no significant differences in the following parameters before and after smoking cessation: systolic blood pressure, diastolic blood pressure, heart rate, triglycerides, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, glucose and hemoglobin A1c. Serum d-ROM levels significantly decreased from 340.7±70.4 to 300.0±43.2 U.CARR (P=0.012), and FMD significantly increased from 3.36±1.26 to 5.25±1.33% (P=0.00067) after smoking cessation. There was an inverse correlation between FMD and serum d-ROM levels (R=-0.377; P=0.043). Our observations suggest that varenicline-assisted smoking cessation restores vascular endothelial function, and this is associated with decreased oxidative stress, despite an increase in body weight. As varenicline-assisted smoking cessation possibly has beneficial effects on vascular endothelial function, it might also reduce cardiovascular risk.