Varenicline, an alpha 4 beta 2 nicotinic acetylcholine receptor partial agonist, vs sustained-release bupropion and placebo for smoking cessation - A randomized controlled trial
ABSTRACT The alpha4beta2 nicotinic acetylcholine receptors (nAChRs) are linked to the reinforcing effects of nicotine and maintaining smoking behavior. Varenicline, a novel alpha4beta2 nAChR partial agonist, may be beneficial for smoking cessation.
To assess efficacy and safety of varenicline for smoking cessation compared with sustained-release bupropion (bupropion SR) and placebo.
Randomized, double-blind, parallel-group, placebo- and active-treatment-controlled, phase 3 clinical trial conducted at 19 US centers from June 19, 2003, to April 22, 2005. Participants were 1025 generally healthy smokers (> or =10 cigarettes/d) with fewer than 3 months of smoking abstinence in the past year, 18 to 75 years old, recruited via advertising.
Participants were randomly assigned in a 1:1:1 ratio to receive brief counseling and varenicline titrated to 1 mg twice per day (n = 352), bupropion SR titrated to 150 mg twice per day (n = 329), or placebo (n = 344) orally for 12 weeks, with 40 weeks of nondrug follow-up.
Primary outcome was the exhaled carbon monoxide-confirmed 4-week rate of continuous abstinence from smoking for weeks 9 through 12. A secondary outcome was the continuous abstinence rate for weeks 9 through 24 and weeks 9 through 52.
For weeks 9 through 12, the 4-week continuous abstinence rates were 44.0% for varenicline vs 17.7% for placebo (odds ratio [OR], 3.85; 95% confidence interval [CI], 2.70-5.50; P<.001) and vs 29.5% for bupropion SR (OR, 1.93; 95% CI, 1.40-2.68; P<.001). Bupropion SR was also significantly more efficacious than placebo (OR, 2.00; 95% CI, 1.38-2.89; P<.001). For weeks 9 through 52, the continuous abstinence rates were 21.9% for varenicline vs 8.4% for placebo (OR, 3.09; 95% CI, 1.95-4.91; P<.001) and vs 16.1% for bupropion SR (OR, 1.46; 95% CI, 0.99-2.17; P = .057). Varenicline reduced craving and withdrawal and, for those who smoked while receiving study drug, smoking satisfaction. No sex differences in efficacy for varenicline were observed. Varenicline was safe and generally well tolerated, with study drug discontinuation rates similar to those for placebo. The most common adverse events for participants receiving active-drug treatment were nausea (98 participants receiving varenicline [28.1%]) and insomnia (72 receiving bupropion SR [21.9%]).
Varenicline was significantly more efficacious than placebo for smoking cessation at all time points and significantly more efficacious than bupropion SR at the end of 12 weeks of drug treatment and at 24 weeks.
clinicaltrials.gov Identifier: NCT00141206.
Full-textDOI: · Available from: Mitchell A Nides, Apr 04, 2014
SourceAvailable from: PubMed Central[Show abstract] [Hide abstract]
ABSTRACT: Varenicline, a selective partial agonist/antagonist of the α4β2 nicotinic receptor, has proven effectiveness for smoking cessation by several randomized, controlled trials. Because few studies have evaluated the long-term efficacy of varenicline, we tried to evaluate the smoking status of varenicline users up to 3 years after the initial prescription of the drug. We interviewed varenicline users who were prescribed the drug from June 2007 to May 2010 by telephone, from June 2010 to May 2011. One-hundred and thirty-three of 250 varenicline users (53.2%) were available for the survey. Seven-day continuous abstinence from smoking was adhered to by 17 of 39 respondents (43.6%) at 1 year, and 11 of 36 (30.6%) and 19 of 58 (32.8%) at 2 and 3 years since the first use of varenicline, respectively. Compared to current smokers, successful quitters were older (55.0 years vs. 49.9 years, p=0.01), had better compliance to the 12-week course (27.7 vs. 9.3%, p=0.01), and had taken varenicline longer (10.1 vs. 5.9 weeks, p=0.01). Fifty-four of 71 current smokers (76.1%) were willing to stop smoking in the near future. The preferred ways to cease smoking were will-power (48.1%), varenicline (25.9%), nicotine replacement therapy (11.1%), and others (14.9%). Smokers should be encouraged to stick to the proven way for recommended period of time for successful cessation of smoking.Tuberculosis and Respiratory Diseases 04/2015; 78(2):92-98. DOI:10.4046/trd.2015.78.2.92
[Show abstract] [Hide abstract]
ABSTRACT: Introduction Tobacco smoking is the leading cause of cardiovascular morbidity and mortality and quitting tobacco use should be fundamental for cardiovascular patients. Varenicline is a smoking cessation pharmacological therapy able to improve the possibilities to successfully achieve this result. In 2011 the US Food and Drug Administration issued a safety announcement that varenicline may be associated with an increased risk of certain cardiovascular adverse events in patients who have cardiovascular disease. Following studies found no significant increase in cardiovascular serious adverse events associated with varenicline. For the first time in the literature, we describe the case of a cardiopathic hard smoker who received varenicline for 9 months without any side effect. By describing this case we want to underline the safety of varenicline, to illustrate the setting and the method that we used to support him and to underline the importance of promoting smoking cessation in heart patients. Case presentation Varenicline was used to promote smoking cessation in a 52-year-old Caucasian man who smoked 40 cigarettes per day, despite two ischemic cardiovascular events. He asked for a consultation in a pharmacy’s smoking cessation service and after the assessment phase varenicline was prescribed. Due to his difficulty to quit smoking and given his good tolerance of the drug, we extended the treatment with varenicline to 9 months in order to achieve and maintain a complete smoking abstinence; intensive behavioural counselling was combined with the pharmacological therapy. By using exhaled carbon monoxide measurement we assessed smoking abstinence up to 2 years. Conclusions The use of varenicline for a period longer than 6 months has not been described in the literature, particularly in heart patients. The extended varenicline therapy was clinically monitored and allowed the patient to consolidate his abstinence; the intensive behavioural counselling helped him to overcome his strong psychological dependence. Promoting smoking cessation in people who have cardiovascular disease is crucial. Currently available medications, such as varenicline, increase the chances of success and the risk of possible side effects is outweighed by the lifetime benefits and we hope that clinicians use them more frequently and confidently.Journal of Medical Case Reports 02/2015; 9(1). DOI:10.1186/1752-1947-9-29
[Show abstract] [Hide abstract]
ABSTRACT: Smoking is a modifiable risk factor for morbidity and mortality caused by cancer, cardiovascular diseases, respiratory diseases, and many other diseases. Given the large population size and high prevalence of smoking in Asia, successful smoking cessation could potentially prevent the large number of premature deaths in Asians. However, most dependent smokers cannot successfully quit smoking due to nicotine addiction, and they need professional help and smoking cessation therapies. Varenicline is a highly selective partial agonist for the nicotinic acetylcholine receptor α4β2 subtype, which is believed to be responsible for mediating the reinforcing properties of nicotine. This article is a narrative review, which summarizes the smoking cessation efficacy, side effects, and cost utilities of varenicline in Asians. From this review, we conclude that varenicline is an effective medication that could assist smoking cessation in the Asian populations. The adverse events of varenicline are tolerable, and the most common events were nausea and abnormal dreams. Both the efficacy and tolerance of varenicline in Asians are similar to that in Western populations. Considering the cost utilities, varenicline should be recommended for use in smoking cessation and be covered by medical insurance in most Asian countries.Patient Preference and Adherence 01/2015; 9:579-84. DOI:10.2147/PPA.S60785 · 1.49 Impact Factor