Varenicline in Smoking Cessation Therapy - Varenicline in Smoking Cessation Therapy
The goal of the trials were to evaluate treatment with varenicline, a nicotine acetylcholine receptor agonist, compared with bupropion (Zyban) and placebo for smoking cessation.
Patients Enrolled: 2,052
Mean Follow Up: One year
Mean Patient Age: Mean age 44 years
Age 18-75 years, smoked at least 10 cigarettes per day for the past year, motivated to quit smoking, and bupropion naive
Four-week continuous abstinence rate (carbon dioxide confirmed) during weeks 9-12
Continuous abstinence rate (carbon dioxide confirmed) during weeks 9-52
Two trials were conducted with the same design scheme, as follows. Patients were randomized in a double-blind manner to 12 weeks of treatment with varenicline (1 mg bid) (n = 352 in study 1 and n = 344 in study 2), bupropion (Zyban) (150 mg bid for 12 weeks) (n = 329 in study 1 and n = 342 in study 2), or placebo (n = 344 in study 1 and n = 341 in study 2). Patients were followed for an additional 40 weeks after study drug.
Mean duration of smoking was 24 years in study 1 and 26 years in study 2. The primary endpoint of 4-week continuous quit rate during weeks 9-12 was higher in the varenicline group (44.0% in study 1 and 43.9% in study 2) compared with the bupropion group (29.5% in study 1 and 29.8% in study 2, p < 0.0001) and the placebo group (17.7% in study 1 and 17.6% study 2, p < 0.0001). The secondary endpoint of continuous abstinence rate during weeks 9-52 was also higher in the varenicline group (21.9% in study 1 and 23.0% in study 2) compared with the bupropion group (16.1% in study 1 and 14.6% in study 2, p < 0.01) and the placebo group (8.4% in study 1 and 10.3% in study 2, p < 0.0001).
Adverse events resulting in study drug discontinuation were higher in the varenicline groups and bupropion groups compared with placebo (8.6%, 15.2%, and 9.0%, respectively in study 1 and 10.5%, 12.6%, and 7.3%, respectively in study 2). Nausea was the main adverse event, although most patients described the symptoms as mild.
Among long-term smokers, treatment with varenicline was associated with a higher smoking cessation rate compared with treatment with bupropion or placebo.
Smoking is a leading, preventable cause of cardiovascular morbidity and mortality. Varenicline is a nicotine acetylcholine receptor agonist that has the potential to relieve nicotine cravings and withdrawal symptoms and reduce the nicotine reinforcement associated with smoking. The present two studies both showed parallel improvements in both smoking cessation as well as continued abstinence with varenicline. While adverse events were higher with varenicline, the events were generally mild.
Study 1: Gonzales D, Rennard SI, Nides M, et al. Varenicline, an alpha-4-beta-2 nicotinic acetylcholine receptor partial agonist, vs sustained-release bupropion and placebo for smoking cessation: a randomized controlled trial. JAMA 2006;296:47-55.
Study 2: Jorenby DE, Hays JT, Rigotti NA, et al. Efficacy of varenicline, an alpha-4-beta-2 nicotinic acetylcholine receptor partial agonist, vs placebo or sustained-release bupropion for smoking cessation: a randomized controlled trial. JAMA 2006;296:56-63.
Presented by Dr. Serena Tonstad at the American Heart Association Scientific Sessions, Dallas, Texas, November 2005.
Clinical Topics: Heart Failure and Cardiomyopathies
Keywords: Nausea, Nicotinic Agonists, Substance Withdrawal Syndrome, Quinoxalines, Tobacco Use Disorder, Receptors, Cholinergic, Smoking Cessation, Benzazepines, Bupropion
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