Clinical research studyBupropion for Smokers Hospitalized with Acute Cardiovascular Disease
Introduction
Cigarette smoking increases the risk of cardiovascular disease.1 Stopping smoking, even after clinical disease develops, reduces cardiovascular risk.2 Smoking cessation after myocardial infarction reduces cardiovascular mortality by 36-46%, is highly cost-effective, and is recommended by clinical guidelines for secondary cardiovascular disease prevention.3, 4, 5, 6
Hospitalization for cardiovascular disease offers an opportunity to initiate smoking cessation.7 In this setting, brief bedside counseling followed by telephone counseling after discharge increases smoking cessation rates.8, 9, 10, 11, 12 This evidence led the Joint Commission on the Accreditation of Health Care Organizations to make smoking cessation assistance after acute myocardial infarction a quality-of-care measure for U.S. hospitals.13 However, even with state-of-the-art intervention, over 40% of smokers resume smoking after myocardial infarction.8, 10, 11 Starting pharmacotherapy during hospitalization might increase cessation rates after discharge. Bupropion and nicotine replacement are part of evidence-based smoking cessation treatment for outpatients and are safe for patients with stable cardiovascular disease,14, 15, 16 but neither drug has been tested in hospitalized patients with acute cardiovascular disease.
Bupropion has a potential advantage in this setting because of its antidepressant action. Depression after hospitalization for myocardial infarction or unstable angina is associated with increased cardiovascular mortality independent of smoking.17, 18, 19, 20 In one trial of outpatients with cardiovascular disease, bupropion was safe and effective, but smokers with a recent acute event were excluded.15 Questions about bupropion’s safety were raised by post-marketing case reports of deaths, cardiovascular events, and severe hypertension in patients taking the drug for smoking cessation.21, 22 Uncontrolled studies of bupropion in depressed patients with cardiovascular disease reveal a 5 mmHg increase in systolic and diastolic blood pressure but no effect on heart rate, rhythm, or contractility.23, 24 We tested the efficacy and safety of bupropion for smoking cessation in smokers who were hospitalized for acute cardiovascular disease. We hypothesized that adding bupropion to a validated smoking cessation counseling program would produce more smoking cessation than the counseling program plus a placebo and that treatment would not be accompanied by an increase in clinically important cardiovascular events.
Section snippets
Methods
A randomized double-blind placebo-controlled trial tested the safety and efficacy of sustained-release bupropion when added to cognitive-behavioral counseling for smoking cessation in smokers hospitalized with acute cardiovascular disease. Subjects were recruited from 5 hospitals. Institutional review boards at each site approved the study. An external data safety and monitoring board monitored the trial.
Subjects
Between October 1, 1999, and October 31, 2002, we identified 4188 smokers hospitalized with acute cardiovascular disease (Figure 1). Of these, 2672 (64%) were ineligible. The major reasons were residence outside geographic area, seizure risk, excess alcohol use, uncontrolled hypertension, recent bupropion use, and cognitive or psychiatric impairment. Eligible smokers did not differ from ineligible smokers in mean age (60 vs 62 years, P=.35) or gender (67% vs 70% male, P=.25) but were more
Discussion
In this randomized trial of smokers hospitalized with acute cardiovascular disease, bupropion did not increase long-term cessation rates over a “best-practice” smoking counseling program, but it did have a short-term benefit. At the end of treatment, we observed a trend toward bupropion efficacy that was statistically significant after adjustment for potential confounders and in the subgroup of patients compliant with the study drug. Given the overall evidence supporting the efficacy of
Acknowledgments
This study was funded by grants from NHLBI (#R01 HL 61779 and #K24-HL04440), the NIH General Clinical Research Centers Program (#M01-RR-01066) and an unrestricted research grant from GlaxoSmithKline, Inc (GSK). GSK provided free drug and placebo and an unrestricted research grant to permit data collection to be completed when NHLBI funds were exhausted.
We are grateful to the participating hospitals (Massachusetts General Hospital, Brigham and Woman’s Hospital, and Boston Medical Center in
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Cited by (0)
Trial registration: ClinicalTrials.gov (#NCT00181818)
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Dr. Pasternak is now affiliated with Merck, Inc. Dr. Torres-Finnerty is now at Beth Israel Deaconess Medical Center & Harvard Medical School.