To the Editor:
The Transdermal Nicotine in Cardiac Patients Study was a randomized, double-blind, placebo-controlled trial designed to test the safety and efficacy of transdermal nicotine as an aid in the cessation of smoking in patients with at least one type of major cardiovascular disease. A total of 584 outpatients receiving care from 10 Veterans Affairs medical centers participated in the trial. The initial report of this trial described the safety of the therapy in this high-risk outpatient population; however, 24 weeks after randomization, only 14 percent of the subjects in the nicotine-treatment group and 11 percent of those in the placebo group were abstinent from smoking (P=0.67), suggesting that the efficacy of the therapy was limited. (1)
At 48 weeks after randomization, 10 percent of subjects in the nicotine group and 12 percent of those in the placebo group were abstinent (P=0.41). These data confirm the lack of effect observed at 24 weeks, and are inconsistent with the published results of behavioral-intervention studies in patients with acute cardiac disease and most other clinical trials of transdermal nicotine. (2)
There are several potential explanations for the lack of efficacy of transdermal nicotine in this trial. The subject population differed from that of many earlier studies in that the participants in this study were older (mean age, 61 years), received care at Veterans Affairs medical centers for numerous chronic medical problems, often had psychiatric or substance-abuse disorders or histories of such disorders, and had experienced multiple failed attempts at quitting. Also, the behavioral component of the intervention was brief (four visits of 10 to 15 minutes each).
Another recent trial in which the transdermal nicotine patch, bupropion, combination therapy with the patch and bupropion, and placebo were compared showed no benefit of the patch as compared with placebo. (3) Earlier published trials of the efficacy of the patch may have favored positive outcomes through the selection of optimal subjects, or the results of trials with negative outcomes may not have been published. (4) Other investigators have observed a downward trend in rates of abstinence over the past two decades and have attributed the observation to changes in the demographic characteristics of smokers. (5)
These data suggest that there is a need to conduct randomized trials of pharmacologic aids to smoking cessation in various subgroups of smokers and treatment settings before their effectiveness can be assumed. Such subgroups include both older and younger smokers, patients with peripheral vascular disease, those with chronic obstructive pulmonary disease, and those with a variety of psychiatric conditions. Smokers with these disorders are likely to be underrepresented in clinical trials, particularly those sponsored by the pharmaceutical industry.
It is critical that effective strategies be developed for patients with cardiovascular disease, because smoking cessation is associated with substantial reductions in morbidity and mortality. However, it cannot be assumed that the results of clinical trials that are conducted in young, healthy persons will be replicated in such patients.
Anne M. Joseph, M.D., M.P.H.
Minneapolis Veterans Affairs Medical Center
Minneapolis, MN 55417
David O. Antonnucio, Ph.D.
Reno Veterans Affairs Medical Center
Reno, NV 89520
References
1.
Joseph AM, Norman SM, Ferry LH, et al. The safety of transdermal nicotine as an aid to smoking cessation in patients with cardiac disease. N Engl J Med 1996;335:1792-8.
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2.
Fiore MC, Bailey WC, Cohen SJ, et al. Smoking cessation. Clinical practice guideline no. 18. Washington, D.C.: Government Printing Office, 1996. (AHCPR publication no. 96-0692.)
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3.
Jorenby DE, Leischow SJ, Nides MA, et al. A controlled trial of sustained-release bupropion, a nicotine patch, or both for smoking cessation. N Engl J Med 1999;340:685-91.
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4.
Irvin JE, Brandon TH. The increasing recalcitrance of smokers in clinical trials. Presented at the 5th Annual Meeting of the Society for Research on Nicotine and Tobacco, San Diego, Calif., March 1999.
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5.
Ioannidis JP. Effect of the statistical significance of results on the time to completion and publication of randomized efficacy trials. JAMA 1998;279:281-6.
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