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CV Safety of Varenicline, Bupropion, and Nicotine Patch in Smokers
Study Questions:
Should we be concerned about the cardiovascular (CV) risk of smoking cessation treatments?
Methods:
A double-blind, randomized, triple-dummy, placebo, and active-controlled trial (EAGLES [Evaluating Adverse Events in a Global Smoking Cessation Study]) and its nontreatment extension trial was conducted at 140 multinational centers. Smokers, with or without established psychiatric diagnoses, who received at least one dose of study medication (n = 8,058), as well as a subset of those who completed 12 weeks of treatment plus 12 weeks of follow-up and agreed to be followed up for a total of 52 weeks (n = 4,595), were included. Active treatments included varenicline, 1 mg twice daily; bupropion hydrochloride, 150 mg twice daily; and nicotine replacement therapy, 21 mg/d patch with tapering. The primary endpoint was the time to development of a major adverse cardiac event (MACE; CV death, nonfatal myocardial infarction [MI], or nonfatal stroke) during treatment; secondary endpoints were the occurrence of MACE and other pertinent CV events (MACE+: MACE or new-onset or worsening peripheral vascular disease [PVD] requiring intervention, coronary revascularization, or hospitalization for unstable angina).
Results:
Of the 8,058 participants, 3,553 (44.1%) were male (mean [standard deviation] age, 46.5 [12.3] years). About 6% had coronary heart disease and PVD, 6% had diabetes, and the baseline Framingham 10-year CV risk score was about 8%. The incidence of CV events during treatment and follow-up was low (<0.5% for MACE; <0.8% for MACE+) and did not differ significantly by treatment. No significant treatment differences were observed in time to CV event, blood pressure, or heart rate. There was no significant difference in time to onset of MACE for either varenicline or bupropion treatment versus placebo.
Conclusions:
There appears to be no increased CV risk associated with smoking cessation treatments in the general population of smokers.
Perspective:
Cigarette smoking is associated with an increased risk of MI, stroke, PVD, atrial fibrillation, sudden death, worsening heart failure, and increased rates of thrombosis following coronary revascularization. An observational study concluded that varenicline appeared to be associated with an increased risk of CV, but not neuropsychiatric events. This study was requested by US and European drug agencies, and provides convincing evidence that in a general population of smokers, smoking cessation medications do not increase the risk of serious CV events. The study was underpowered to assess the safety of the interventions in patients with known atherosclerotic CV disease, particularly those with acute or unstable CV disease. Nevertheless, the benefit compared to the risk of employing smoking cessation treatments is overwhelming in favor.
Keywords: Angina, Unstable, Atrial Fibrillation, Blood Pressure, Bupropion, Coronary Artery Disease, Death, Sudden, Diabetes Mellitus, Heart Failure, Heart Rate, Myocardial Infarction, Myocardial Revascularization, Nicotine, Peripheral Vascular Diseases, Primary Prevention, Risk Assessment, Smoking, Smoking Cessation, Stroke, Thrombosis, Tobacco Use Cessation Devices
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