Mitchell A. Nides

Smoking cessation in patients with chronic obstructive pulmonary disease: a double-blind, placebo-controlled, randomised trial

BACKGROUND Tobacco smoking is associated with chronic obstructive pulmonary disease (COPD) in more than 80% of cases. Our aim was to investigate the effect of sustained-release bupropion (amfebutamone) (SR) in promoting abstinence from smoking in patients with COPD. METHODS In a double-blind, randomised, placebo-controlled trial 404 individuals with mild or moderate COPD who smoked 15 or more cigarettes per day, were assigned bupropion SR (150 mg twice daily) or placebo for 12 weeks. All patients received smoking cessation counselling. Study medication was taken for 1 week before patients attempted to stop smoking. The primary efficacy endpoint was the complete and continuous abstinence from smoking from the beginning of week 4 to the end of week 7. Participants were followed up at month 6. Analysis was by intention to treat. FINDINGS All patients were chronic smokers with a smoking history of about 51 pack-years. Continuous smoking abstinence rates from week 4 to 7 were significantly higher in participants receiving bupropion SR than in those receiving placebo (28% [57/204] vs 16% [32/200], p=0.003). Continuous abstinence rates from weeks 4 to 12 (18% [36/204] vs 10% [20/200]) and weeks 4 to 26 (16% [32/204] vs 9% [18/200]) were also higher in participants receiving bupropion SR than in those taking placebo (p<0.05). Furthermore, symptoms of tobacco craving and withdrawal were attenuated in those receiving bupropion SR. Seven individuals discontinued study medication because of adverse events. INTERPRETATION Bupropion SRis a well-tolerated and effective aid to smoking cessation in people with mild to moderate COPD.

Bupropion SR as an aid to smoking cessation in smokers treated previously with bupropion: a randomized placebo-controlled study.

Many persons who attempt to quit smoking have made previous unsuccessful attempts to quit with pharmacologic aids. An understanding of the impact of these previous attempts to quit is vital for selecting medications that may be more successful in a future attempt to quit. In particular, the effect of repeated use of bupropion SR (Zyban; INN, amfebutamone) on abstinence rates has not been studied previously.

Update on Pharmacologic Options for Smoking Cessation Treatment

Although the proportion of the adult population in the United States that smokes has decreased steadily, the rate of successful quit attempts is still low. Smokers develop nicotine dependence that resembles other addictions, and may require multiple attempts and long-term treatment to sustain abstinence. Currently available first-line agents for smoking cessation therapy include nicotine replacement therapy, which is available in several formulations, including transdermal patch, gum, nasal spray, inhaler, and lozenge; bupropion, an atypical antidepressant; and varenicline, a partial agonist of the alpha(4)beta(2) nicotinic acetylcholine receptor that was recently developed and approved specifically for smoking cessation therapy. Second-line agents are nortriptyline, a tricyclic antidepressant agent, and clonidine, an antihypertensive drug. With the exception of varenicline, which has been shown to offer significant improvement in abstinence rates over bupropion, all of the available treatments appear similarly effective. However, the adverse event profiles of nortriptyline and clonidine make them more appropriate for second-line therapy, when first-line treatments have failed or are not tolerated. Rimonabant, a cannabinoid-1 receptor antagonist that was being developed for smoking cessation, received a nonapprovable letter from the FDA in 2006 and there is no further information as to whether development for this indication is continuing for this agent. Nicotine vaccines are under investigation and offer promise, especially for relapse prevention. Ultimately, selection of pharmacologic agent should be based on the patients comorbidities and preferences, as well as on the agents adverse event profile.

Varenicline versus bupropion SR or placebo for smoking cessation: a pooled analysis.

OBJECTIVES To evaluate vareniclines efficacy for smoking cessation versus bupropion SR and placebo and to explore whether factors typically predictive of abstinence influence vareniclines efficacy versus placebo, as measured by the week 9-12 continuous abstinence rate (CAR9-12). METHODS Smokers in 2 randomized, placebo-controlled trials received varenicline 1 mg BID (n=696), bupropion SR 150 mg BID (n=671), or placebo (n=685) for 12 weeks. Nontreatment followup lasted 40 weeks. RESULTS CAR(9-12) was greater for varenicline (44.0%) versus bupropion SR (29.7%; P<0.0001) and placebo (17.7%; P<0.0001). CAR(9-12) for varenicline versus placebo was not affected by age, gender, or nicotine dependence level. CONCLUSIONS Varenicline was more efficacious than bupropion SR or placebo. Vareniclines efficacy versus placebo was not influenced by factors predictive of abstinence.

Effects of Multiple Attempts to Quit Smoking and Relapses to Smoking on Pulmonary Function

The effect of intermittent smoking on pulmonary function was assessed among participants in the Lung Health Study, 5887 adult smokers with evidence of early chronic obstructive pulmonary disease (COPD), followed up for 5 years. The mean annual rate of loss in FEV1% of predicted after year 1 was smallest for those who quit at some point during the first year of the study and stayed quit (-0.33%/year, +/-0.05%), intermediate for those who smoked intermittently during the study (-0.58%/year, +/-0.05%) and greatest for those who continued to smoke throughout the study (-1.18%/year, +/-0.03%). Surprisingly, those who made several attempts to quit smoking had less loss of lung function at comparable cumulative doses of cigarettes than those who continued to smoke. Quitting smoking for an interval followed by relapse to smoking appeared to provide a measurable and lasting benefit in comparison to continuous smoking. In this early COPD population, not only quitting smoking but attempts to quit smoking can prevent some loss of lung function. These results provide some encouragement to exsmokers who relapse on their way to complete cessation.

Smoking reduction and the rate of decline in FEV1: results from the Lung Health Study

Previous findings from the Lung Health Study have shown that smoking cessation and sustained abstinence substantially reduce the rate of decline in forced expiratory volume (FEV1) among smokers with early chronic obstructive pulmonary disease (COPD) when compared with continuing smoking. Intermittent quitters demonstrated rates of FEV1 decline intermediate between those of sustained quitters and continuing smokers. In this study, data from 1,980 participants were analysed from 10 centres of the Lung Health Study in the USA and Canada. All participants were smokers with mild-to-moderate COPD who were unable to quit smoking at any time during the 1st yr of the study. No linear relationship was found between reduction in cigarettes per day and changes in FEV1 during the 1st yr of the study. However, examination of the data revealed that this relationship was nonlinear. Further analysis found that smokers who reduced their cigarettes per day to very low amounts had smaller declines in FEV1 than those who did not. Reduction in cigarettes per day was associated with only minimal changes in the presence of chronic respiratory symptoms. In conclusion, compensatory changes in smoking behaviour may account for the limited and unpredictable impact of smoking reduction on lung function decline and symptom prevalence when compared with smoking cessation.

Weight Gain as a Function of Smoking Cessation and 2-Mg Nicotine Gum Use Among Middle-Aged Smokers With Mild Lung Impairment in the First 2 Years of the Lung Health Study

The extent and predictors of weight change were assessed among sustained nonsmoking special intervention participants in the Lung Health Study. The intervention included a 12-session group program and 2-mg nicotine gum. At 12 months, female sustained quitters (SQs; n = 248) had gained a mean of 8.4% (5.3 kg) of their baseline weight, whereas male SQs (n = 443) had gained 6.7% (5.5 kg). By 24 months, female SQs had gained 9.8% of their baseline weight compared with 6.9% for men. Nicotine gum usage delayed a portion of the weight gain. Multiple regression analysis showed that weight gain at 12 months was associated with a higher baseline salivary cotinine level, a lower baseline body mass index, drinking less alcohol per week, and a lower cotinine level at 12 months (indicating less or no nicotine gum use). We conclude that moderate weight gain is a long-term consequence of smoking cessation--a portion of which can be delayed with 2-mg nicotine gum.

Late-term smoking cessation despite initial failure: an evaluation of bupropion sustained release, nicotine patch, combination therapy, and placebo

OBJECTIVE The purpose of this study was to evaluate the efficacy of long-term use of bupropion sustained release (SR), the nicotine patch, and the combination of these 2 treatments in patients who initially failed treatment. METHODS This was a post hoc analysis of a multicenter, double-blind, randomized, placebo-controlled clinical trial in 893 smokers. Patients were randomly assigned to 9 weeks of treatment with placebo (n = 160), bupropion SR (n = 244), nicotine patch (n = 244), or a combination of nicotine patch and bupropion SR (n = 245). The study was originally designed with a follow-up period of 52 weeks. In this analysis, short-term success was defined as smoking cessation after 14 or 21 days of therapy and long-term success was defined as smoking cessation after >21 days of therapy. Patients who did not achieve short-term success were evaluated for long-term success at week 9 (end of treatment), 6 months, and 1 year after the start of the study. RESULTS The mean age of the smokers was 44 years. The majority (93%) of patients were white, and 52% were female. The study subjects smoked an average of 27 cigarettes per day. Among the 467 patients who initially failed treatment in the first 3 weeks, treatment with bupropion SR alone and in combination with the nicotine patch produced significant increases in successful smoking cessation rates from weeks 4 to 9 (19% bupropion SR or combination, 7% nicotine patch, 7% placebo), at month 6 (11% bupropion SR, 13% combination, 2% nicotine patch, 3% placebo), and at month 12 (10% bupropion SR, 7% combination, 2% nicotine patch, 1% placebo) (P < 0.05 for bupropion SR and combination vs nicotine patch or placebo). CONCLUSION Among patients who initially failed treatment, continued therapy with bupropion SR, either alone or in combination with the nicotine patch, resulted in significantly higher short- and long-term smoking cessation rates than treatment with the nicotine patch alone or placebo.

Nicotine blood levels and short-term smoking reduction with an electronic nicotine delivery system.

OBJECTIVES To evaluate nicotine delivery from the NJOY® King Bold Electronic Nicotine Delivery System (ENDS) and its short-term potential for smoking reduction or cessation. METHODS One week of ad libitum use was followed by measurements of plasma nicotine, heart rate, and craving and withdrawal after 12 hours of nicotine abstinence in 25 adult smokers not interested in quitting. RESULTS After 5 minutes of use, blood nicotine levels increased by a mean of 3.5 ng/mL (p < .001), heart rate increased, and craving was reduced by 55%. Cigarettes per day were reduced by 39% during the test week, and perceptions of use for reduction or cessation were positive. CONCLUSIONS The NJOY® King Bold ENDS delivers nicotine and led to short-term smoking reduction.

Relations of cotinine and carbon monoxide to self-reported smoking in a cohort of smokers and ex-smokers followed over 5 years

We describe the persistence of discrepancies between biochemical measures of smoking and self-reported smoking status in a cohort of clinical trial participants across 5 years. The Lung Health Study, a randomized trial in 10 clinical centers in North America, enrolled 3923 participants in smoking intervention and 1964 in usual care in 1987 and 1988. Smoking status was assessed at baseline and at five annual follow-up visits by self-report, salivary cotinine and expired-air carbon monoxide. Compared to self-report, sensitivity and specificity of cotinine and carbon monoxide were similar across 5 years. Evidence of error in self-reports of quitting smoking persisted across 5 years, although it declined over time. Multivariate models confirmed that self-report bias was characteristic of the early years in the study. Significant covariates differed between cotinine and carbon monoxide models. When cotinine was used for verification, about half of the individuals in the smoking intervention group with self-report bias at the first year continued to exhibit bias for 5 years. In absolute terms, the errors associated with measurement were small, but they persisted over 5 years. Some differences appeared to be related to the distinction that carbon monoxide verification was immediate, while cotinine verification was deferred.