December 13, 2012
FDA is informing patients and healthcare providers about the results of a large meta-analysis assessing the cardiovascular safety of varenicline (Chantix®). The meta-analysis was initiated last year after the FDA informed the public of a possible increased risk of cardiovascular events associated with varenicline. The analysis included over 7,000 patients from 15 clinical trials comparing varenicline to placebo. The primary outcome evaluated was a composite endpoint including cardiovascular-related death and nonfatal stroke or heart attack. The rate of major cardiovascular adverse events was low in both the varenicline (0.31%) and placebo (0.21%) groups, with a hazard ratio of 1.95 (95% CI 0.79 to 4.82). These results were not statistically significant, however, the incidence of cardiovascular events was consistently higher with varenicline than placebo across several analyses. The rate of cardiovascular-related death was lower with varenicline (0.05%) than placebo (0.07%), as was the rate of death due to any cause (varenicline 0.14% vs placebo 0.25%). However, these results were not statistically significant.
In June, 2011, FDA reviewed new clinical trial results for varenicline in patients with stable cardiovascular disease. Increased incidences of nonfatal myocardial infarction, peripheral vascular disease, and need for coronary revascularization were observed in patients treated with varenicline compared to placebo. However, this study was not powered to detect statistical differences in safety outcomes, and the overall incidence of these events in treatment and control groups was small. This study was included in the meta-analysis.
Varenicline labeling has been updated to include the results of the meta-analysis. The label was updated in 2011 to include safety and efficacy information in patients with cardiovascular disease and chronic obstructive pulmonary disease (COPD). Varenicline was superior to placebo for smoking cessation in patients with underlying cardiovascular disease and in patients with mild- to-moderate COPD. The updated labeling also includes new information on dates to quit smoking. Patients can either choose to quit 7 days after starting varenicline or they can choose a date between days 8 to 35 after starting varenicline.
Varenicline is a partial nicotine agonist used to aid smoking cessation. Smoking is a substantial and independent risk factor for cardiovascular disease. Weigh the risks and benefits of varenicline before prescribing this medication and encourage patients to review the varenicline Medication Guide. Patients should notify their providers if they experience symptoms of cardiovascular disease.
Additional information is available at the following links:
- MedWatch alert
- Drug Safety Communication:
December 13, 2012; July 26, 2011; June 20, 2011; University of Utah, Drug Information Service. Copyright 2011, Drug Information Service, University of Utah, Salt Lake City, UT.