Elsevier

The Lancet

Volume 357, Issue 9268, 19 May 2001, Pages 1571-1575
The Lancet

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

https://doi.org/10.1016/S0140-6736(00)04724-3Get rights and content

Summary

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 SR is a well-tolerated and effective aid to smoking cessation in people with mild to moderate COPD.

Introduction

Chronic obstructive pulmonary disease (COPD) is widespread and preventable. The disease is one of the leading causes of morbidity and mortality worldwide and is increasing in prevalence, especially in less-developed countries. Estimates suggest that in less than 20 years, COPD will be one of the five leading global medical burdens on society.1 The prevention of COPD, therefore, has huge social and economic implications.

The most important intervention in the management of COPD, as recommended by the Global Initiative for Chronic Obstructive Lung Diseases, is smoking cessation.2 Tobacco smoking leads to COPD in more than 80% of cases,3 and stopping smoking reduces the accelerated decline in pulmonary function and improves long-term prognosis.4 Smoking-cessation programmes, as a primary method of disease prevention, are cost effective and have better economic value than many life-preserving medical interventions.5, 6 Well implemented programmes could, therefore, be judged the single most important therapeutic intervention in the treatment of COPD.

Bupropion (amfebutamone) sustained release (SR) is the first non-nicotine-based pharmacotherapy for smoking cessation. The treatment has been available in USA since 1997 and has received marketing approval throughout most of the European Union. In smokers taking bupropion SR, cessation rates are about double those seen with placebo.7, 8 However, there are no data on smoking cessation rates for bupropion SR in smokers with COPD, a population that has additional barriers for success in smoking cessation such as older age, higher pack-year history, and higher nicotine-addiction scores than previously studied populations.

We did a multicentre, double-blind, placebo-controlled randomised study to assess the efficacy of a 12-week course of bupropion SR in helping patients with stage I and II COPD to stop smoking. Continuous abstinence from smoking from week 4 to the end of week 7 was our primary endpoint. We also made secondary measurements of efficacy throughout the treatment and follow-up phases, and based subgroup analyses on participant characteristics and smoking histories.

Section snippets

Patients

The study population consisted of current smokers with stage I or stage II COPD. All patients were aged 35 years or older, had smoked 15 cigarettes or more per day for the previous year, and had not stopped smoking for more than 3 months during that year. All participants were motivated to stop smoking.

Recruitment procedures for this study were consistent across all study sites. We recruited potential study participants by means of print and radio advertisements and screened them specifically

Results

411 patients were enrolled (350 stage-I COPD, 61 stage-II COPD), of whom 404 took at least one dose of study medication and comprised the intention-to-treat population. The number of patients enrolled by each centre ranged from 15 to 56. Thus, no one centre contributed more than 14% of the study population. 200 individuals received placebo and 204 received bupropion SR (figure 1). The smoking histories of all randomised participants in each treatment group were closely similar for cigarettes

Discussion

Smoking cessation is the most important approach to the treatment of COPD.17, 18 Our results show that bupropion SR nearly doubles the rate of abstinence from smoking over 12 weeks in smokers with mild-to-moderate COPD compared with placebo. This advantage over placebo continued for 3 months after discontinuation of the drug.

The smokers in our study were older, less healthy, and had smoked more cigarettes for longer periods than participants in previous studies of bupropion SR for smoking

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