Varenicline for smoking cessation: A review of the literature

Background: Smoking is the leading preventable risk to human health. Various agents have been used to promote smoking cessation, but none has had long-term efficacy. Varenicline, a new nicotinic ligand based on the structure of cytosine, was approved by the US Food amd Drug Administration for use as a smoking cessation aid.Objectives: The aims of this review were to provide an overview on the mechanism of action and preclinical and clinical data of the new drug, varenicline, and to discuss the current and future impact of varenicline as a treatment for smoking cessation.Methods: MEDLINE, BIOSIS, and Google scholar databases were searched (March 1, 2007-July 1, 2008) using the terms varenicline, smoking cessation, and nicotinic receptors. Full-text articles in English were selected for reference, and articles presenting the mechanism of action, pharmacokinetics, and data from preclinical and clinical trials were included.Results: The initial literature search yielded 70 papers. A total of 20 articles fulfilled the inclusion criteria. Varenicline, an α₄β₂ nicotinic acetylcholine receptor partial agonist, inhibits dopaminergic activation produced by smoking and decreases the craving and withdrawal syndrome that accompanies cessation attempts. In Phase III clinical trials, the carbon monoxide-confirmed 4-week continuous abstinence rates were significantly higher with varenicline than with buproprion sustained release or placebo for weeks 9 through 12. Varenicline has been found to be well tolerated, with nausea being the most commonly reported (28.1%) adverse event.Conclusions: Varenicline is the first drug for smoking cessation that has been found to have significant effectiveness in long-term relapse prevention (up to 52 weeks). Varenicline, with its unique profile of agonist and antagonist properties, increased cessation rates (both short- and long-term) compared with both placebo and bupropion sustained release.     

5A干预法联合伐尼克兰对COPD稳定期病人戒烟效果的影响

[目的]研究5A干预法联合伐尼克兰对COPD稳定期病人戒烟的效果。[方法]将300例COPD病人随机分为5A戒烟组、伐尼克兰组和联合干预组,每组各100例。5A戒烟组应用5A干预法,伐尼克兰组给予口服伐尼克兰,联合干预组在口服伐尼克兰的基础上给予5A干预法对病人进行戒烟干预,观察3组病人在实施戒烟后1个月、4个月、6个月的戒烟率、肺功能、住院率及生活质量的变化。[结果]联合干预组在干预后1个月、4个月、6个月病人的戒烟率、肺功能、住院率及生活质量明显高于5A戒烟组和伐尼克兰组,差异有统计学意义(P0.05)。[结论]采用5A干预法联合伐尼克兰有利于提高COPD稳定期病人的戒烟率,改善肺功能,减少住院率,提高生活质量。     

The neurobiological basis for partial agonist treatment of nicotine dependence: varenicline

Smoking cessation has major health benefits for men and women of all ages. However, most smokers are addicted to nicotine and fail repeatedly in their attempts to quit. Stimulation of nicotinic receptors in the brain, particularly alpha4beta2 receptors, releases dopamine in the meso-limbic area of the brain and is reinforcing. Nicotine abstinence reduces dopamine release, and this is associated with withdrawal symptoms and craving for nicotine. Eight current pharmacotherapies--bupropion, nortriptyline, clonidine and nicotine patch, gum, inhaler, lozenge and nasal spray--are moderately effective aids to smoking cessation. Each is significantly better than placebo, but approximately 80% of patients using one of these medications return to smoking within the first year. Varenicline, a specific alpha4beta2 nicotinic receptor partial agonist, is a new pharmacotherapy that stimulates dopamine and simultaneously blocks nicotine receptors. Phase II and III trials have yielded promising results suggesting that varenicline could be an important advance in the treatment of nicotine dependence.     

Predictors of Lapse and Relapse to Smoking in Successful Quitters in a Varenicline Post Hoc Analysis in Japanese Smokers

Background

The efficacy of the smoking-cessation agent varenicline has been reported in Asian smokers; however, few studies have investigated factors that contribute to lapse and relapse.

Objective

This post hoc analysis aimed to identify predictors of smoking lapse and relapse.

Methods

This was a post-hoc analysis based on a double-blind, placebo-controlled, randomized, parallel-group study in which Japanese smokers (aged 20–75 years) who smoked ≥10 cigarettes/day and were motivated to quit were randomized to receive varenicline (0.25 mg twice daily [BID], 0.5 mg BID, 1 mg BID) or placebo for 12 weeks followed by a 40-week non-treatment follow-up. For inclusion in this analysis, participants must have been nicotine dependent (Tobacco Dependence Screener score ≥5) and must have successfully quit smoking continuously for 4 weeks (weeks 9–12). Lapse was defined by answering yes to ≥1 question in the Nicotine Use Inventory. Relapse was defined by participants having smoked for ≥7 days during follow-up measured by the Nicotine Use Inventory.

Results

Of the 619 randomized individuals, 515 had a Tobacco Dependence Screener score of ≥5, and 277 quit smoking continuously from weeks 9 to 12. Approximately 75% were male, with a mean (SD) BMI of 23.0 (3.0) kg/m². Maximum length of continuous abstinence (CA) during treatment and age (both P < 0.0001) were significant predictors of lapse. Maximum CA (P < 0.0001), age (P = 0.0002), Minnesota Nicotine Withdrawal Scale (MNWS) score for urge to smoke (P = 0.0019), and having made ≥1 serious quit attempt (P = 0.0063) were significant predictors of relapse. For participants with a maximum CA of 4 to 6 weeks versus those with a maximum CA of 10 to 11 weeks, the ORs for lapse and relapse were 4.649 (95% CI, 2.071–10.434) and 3.337 (95% CI, 1.538–7.239), respectively. In participants aged 21–34 years versus those aged 47–72 years, the ORs for lapse and relapse were 3.453 (95% CI 1.851, 6.441) and 3.442 (95% CI 1.795, 6.597), respectively. Participants with a MNWS urge to smoke score of 2 to 4 versus 0 had an OR for relapse of 3.175 (95% CI, 1.166–8.644). Participants having made ≥1 versus no serious quit attempts had an OR for relapse of 2.108 (95% CI, 1.168–3.805).

Conclusion

Shorter maximum CA and younger age at quit attempt were associated with increased risk of lapse and relapse. Higher MNWS urge to smoke score and having made ≥1 serious quit attempt were associated with increased relapse risk. ClinicalTrials.gov identifier: NCT00139750.     

Cochrane系统评价的基本方法

Cochrane系统评价是Cochrane协作网成员在Cochrane协作网统一工作手册的指导下所作的系统评价,是循证医学的临床实践指南,通过收集、汇总和评价原始临床研究结果,得出有关干预措施的综合结论,为临床实践和卫生决策提供真实、可靠的证据。与传统综述不同,他采用了科学、明确、可重复的研究方法以减少偏倚因素的影响。了解Cochrane系统评价的基本方法,对进行Cochrane系统评价的研究人员有所帮助。     

Using cost-effectiveness analysis to compare Hospital at Home and in-patient interventions. Part 1

An economic analysis was conducted as an integral part of a comparison of the effectiveness and suitability of Hospital at Home (HaH) and in-patient interventions. The sample comprised of 109 adult primary total joint replacement patients and 21 of their coresident informal carers. The paper is presented in two parts. Part 1 includes the background and rationale for the study and the findings from the comparison of the effectiveness of the two interventions using multiple data collection sources. Data were collected using questionnaires, audit and semi-structured interviews. Hospital at Home was found to be significantly more effective in terms of patient satisfaction and reduced joint stiffness and as least as effective as in-patient care in relation to levels of joint pain, joint disability and incidence of postoperative complications. In addition informal carers reported 107 positive comments compared with 36 negative comments related to HaH care and all except one of the 21 carers would choose HaH again in preference to in-patient care.     

Using cost-effectiveness analysis to compare Hospital at Home and in-patient interventions. Part 2

An economic analysis was conducted as an integral part of a comparison of the effectiveness and suitability of Hospital at Home (HaH) and in-patient interventions. The sample comprised 109 adult primary total joint replacement patients and 21 of their co-resident informal carers. Part 2 is principally a methodology paper and describes how nurses may use a variety of methods to compare cost between treatment modalities. A Cost-Effectiveness Analysis framework uses the data from Paper 1 to calculate the economic feasibility of HaH compared with traditional in-patient interventions as a worked example of how the principles of economic analysis can be used within health care research. The basic information for calculating cost of both interventions was obtained by multiplying the mean length of total treatment days by the cost per treatment day. However calculating and comparing cost for in-patient and HaH modalities was multifaceted and included costs incurred by patients and families as well as any shift in cost from tertiary to community and outpatient services. Application of the cost-effectiveness analysis framework demonstrated that not only was HaH more effective than in-patient care in several aspects, but also it was less costly because of a mean reduction in length of stay of 0.9 days per patient and a significant reduction in cost per treatment day because of removal of hospital overhead costs and reduced special duty payments even when offset against additional transport, community and outpatient costs.     

Smoking cessation interventions in chronic obstructive pulmonary disease and the role of the family: a systematic literature review

AIM: This paper is a report of a systematic review to assess the effectiveness of family-focused smoking cessation interventions for people with chronic obstructive pulmonary disease and to determine what data on families are documented in studies of smoking cessation interventions. BACKGROUND: Chronic obstructive pulmonary disease is a major public health problem and cigarette smoking is the most important factor contributing to its development and progression. However, smoking cessation rates are low and relapse is common. The role of families in smoking cessation efforts has received little attention. METHODS: All studies were included in the review that (i) addressed an evaluation of a psycho-social/educational smoking cessation intervention for people with chronic obstructive pulmonary disease, (ii) addressed some information on the family (i.e. living arrangements, marital status, smoking history of family members, support for quitting) and/or included the family as part of the intervention and (iii) were published between 1990 and 2006. Electronic data sources, existing systematic reviews of smoking cessation interventions and the grey literature were reviewed. RESULTS: Seven studies were included. Six studies (11 papers) included data on marital status, smoking status of household members, support for quitting smoking and related variables. In two of the studies, the variable on the family was used to analyse smoking cessation outcomes. One additional study met the inclusion criterion of an evaluation of a smoking cessation intervention, which also included a family focus in the intervention. CONCLUSION: No conclusions about the effectiveness of a family-focused smoking cessation intervention could be drawn from this review. Further research is needed to determine if a more family-focused intervention, in conjunction with pharmacological and counselling approaches, would lead to improved smoking cessation outcomes.     

A cost-effectiveness analysis of n-3 PUFA (Omacor) treatment in post-MI patients

This study evaluates the cost-effectiveness of Omacor treatment as a standard prevention measure post-MI in the UK. A cost-effectiveness model was developed based on the GISSI-P trial, combining a survival and a Markov model, over a lifetime period. The base case results for Omacor, at 4 years and over a lifetime, respectively, were: cost [corrected] per QALY gained: pound15,189 and 3,723; [corrected] cost per life years gained (LYG): pound12,011 and pound2,812 [corrected] The cost per death avoided at 4 years was pound31,786. Deterministic and probabilistic sensitivity analyses did not change the base case results substantially. The use of Omacor as a standard post-MI prevention treatment seems warranted in the UK, both on the basis of its efficacy, which is in addition to other prophylactic treatments as evidenced by the results of the GISSI-P trial, and on cost-effectiveness grounds - both at 4 years and over a lifetime's time-horizon, using the current cost-effectiveness thresholds.     

Preventive Care in the Emergency Department: Diagnosis and Management of Smoking and Smoking-related Illness in the Emergency Department: A Systematic Review

Smoking remains the leading preventable cause of morbidity and mortality in the United States. The efficacy of emergency department (ED)-based patient screening and counseling for smoking cessation is not currently known. OBJECTIVES: To perform a structured, systematic review of the medical literature to assess the efficacy of limited screening and counseling for tobacco use cessation among adults in the primary care and ED settings, and develop recommendations for emergency physicians based on these data. METHODS: A two-person template-driven review of all English-language articles from Medline, the Cochrane Database, and two recent smoking cessation guidelines, with evidence graded according to the scheme of the U.S. Preventive Services Task Force (USPSTF), was performed. Recommendations were developed, and strength graded, based on this evidence. RESULTS: Of 2,078 citations reviewed, 16 were selected for inclusion, based on their methodologic strength and relevance to emergency medicine. Routine physician screening and counseling may increase quit rates at 6-12 months from 3% (usual care) to 8-11%. Interventions include brief counseling (<3 minutes), possibly supplemented with self-help literature, nicotine replacement therapy (NRT), and follow-up telephone calls. CONCLUSIONS: Strong evidence exists, in the primary care setting, that smoking cessation screening and counseling are effective. Limited data exist for ED-based practice, but, based on the burden of disease, relative ease of intervention, and likely efficacy, routine screening of all patients for tobacco use and referral of smokers to primary care and cessation programs are recommended.     

The cost-effectiveness of bimatoprost 0.03% in the treatment of glaucoma in adult patients--a European perspective

Glaucoma is a condition affecting one or both eyes with raised intraocular pressure (IOP). IOP should be reduced to prevent progression of visual field loss. This study investigates the cost-effectiveness of bimatoprost compared with latanoprost as first-line monotherapies in the treatment of glaucoma in Austria, Finland and France. On the basis of a single multicentre, randomised, investigator-masked controlled trial, a 6- and 12-month cost-effectiveness model was designed following the treatment recommendations from the European Glaucoma Society. Treatment changes due to insufficient IOP reduction and adverse events were included. The cost-effectiveness analysis showed that the need for adjunctive therapy was the major cost driver. On the basis of evidence from the randomised, investigator-masked clinical trial (RCT), the cost-effectiveness analysis found that bimatoprost was a cheaper and a more effective treatment strategy compared with latanoprost. This was true for all three countries and all IOP targets between 13 and 20 mmHg. The cost-effectiveness result may be generalised to a European setting and perspective.