The use of varenicline (Chantix, Pfizer) to stop smoking is associated with a 72 percent increased risk of a serious adverse cardiovascular event, according to an article published July 4 in the Canadian Medical Association Journal.
When varenicline was launched in 2006, the FDA safety reviewers reported that existing data indicated it could raise the risk of adverse cardiac events. Last month, the FDA issued a label update of a boxed warning for Chantix based on a small increased risk of cardiovascular events among smokers with heart disease.
Researchers from Johns Hopkins University School of Medicine in Baltimore, the University of East Anglia in Norwich, England, and Wake Forest Baptist Medical Center in Winston-Salem, N.C., sought to investigate the serious cardiac effects of varenicline in tobacco users (smokers or smokeless tobacco users) compared with placebos in clinical trials. They examined 14 trials that included 8,216 patients (4,908 people on varenicline and 3,308 taking placebos). All trials, except one, excluded people with a history of heart disease.
In the study, 1.06 percent of participants taking varenicline had adverse events compared with 0.82 percent participants on placebo. Seven of the 4,908 people taking varenicline died compared with seven of 3,308 receiving placebo.
"Among tobacco users varenicline use was associated with a significantly increased risk of serious adverse cardiovascular events greater than 72 percent," wrote lead author Sonal Singh, MD, MPH, of Johns Hopkins, and colleagues.
"However, despite achieving more than twofold higher rates of abstinence in the trials, which should potentially induce a cardiovascular benefit, the participants allocated to varenicline experienced an increase in the risk of serious adverse cardiovascular events," they wrote. "These increased risks of adverse cardiovascular events are seen in smokers with or without heart disease.”
They added that the additional risks of depression, agitation and suicidal thoughts which resulted in the FDA issuing a boxed warning—the highest level of warning—for the drug.
Despite study limitations, such as variable data and lack of statistical strength, the researchers concluded that "clinicians should carefully balance the risk of serious cardiovascular events and other serious neuropsychiatric adverse events associated with varenicline against their known benefits on smoking cessation."
In an accompanying commentary, J. Taylor Hays, MD, from the Mayo Clinic in Rochester, Minn., wrote: "Although these results suggest a measure of caution should be taken in prescribing varenicline for tobacco dependence treatment, the small absolute risk of cardiovascular events associated with varenicline treatment is outweighed by the enormous benefit for reducing cardiovascular morbidity and mortality that can be achieved with successful smoking abstinence."
"The risk for cardiovascular events is low and is far outweighed by the benefits of diminishing the truly 'heartbreaking' effects of cigarette smoking," Hays concluded.