Popular smoking cessation drug associated with 72 percent increased risk of serious CV events, study finds

A new study by researchers at Wake Forest Baptist Medical Center, in collaboration with researchers at Johns Hopkins University School of Medicine and the University of East Anglia, in the United Kingdom, shows that the use of varenicline -- marketed by Pfizer under the brand name ChantixTM -- is associated with a 72 percent increased risk of hospitalization due to a serious adverse cardiovascular (CV) event, such as heart attack or arrhythmia.

The study appears in the July 4 issue of CMAJ (the Canadian Medical Association Journal).

"We have known for many years that Chantix is one of the most harmful prescription drugs on the U.S. market, based on the number of serious adverse effects reported to the FDA (U.S. Food and Drug Administration)," said Curt D. Furberg, M.D., Ph.D., a professor of Public Health Sciences at Wake Forest Baptist, lead investigator on the study, and a nationally-recognized leader in drug safety research. "It causes loss of consciousness, visual disturbances, suicides, violence, depression and worsening of diabetes. To this list we now can add serious cardiovascular events."

Heart disease is a common cause of serious illness and death in smokers and is often a reason for people to stop smoking. Varenicline is one of the most commonly used drugs to help people quit smoking worldwide. When varenicline was launched in 2006, the FDA safety reviewers reported that existing data indicated it could raise the risk of adverse cardiac events. The FDA recently updated the label for Chantix based on a small increased risk of cardiovascular events among smokers with heart disease.

The team of researchers sought to investigate the serious cardiac effects of varenicline in tobacco users (smokers or smokeless tobacco users) compared with placebo in clinical trials. They looked at 14 double-blind, randomized, controlled trials that included more than 8,200 patients (4,908 people on varenicline and 3,308 taking placebos). All trials, except one, excluded people with a history of heart disease, and none of the studies followed participants for longer than one year.

In the study, 52 of 4,908 (1.06%) participants taking varenicline had adverse events compared with 27 of 3,308 (0.82%) participants on placebo, while the number of people who died in each group was the same (seven). The majority of study participants were men and averaged less than 45 years of age.

"Among tobacco users varenicline use was associated with a significantly increased risk of serious adverse cardiovascular events greater than 72 percent," the researchers wrote. "These increased risks of adverse cardiovascular events are seen in smokers with or without heart disease."

The researchers noted additional risks of using the drug, found in previous studies, that led to an existing box warning from the FDA -- risks of depression, agitation and suicidal thoughts.

"People should be concerned," said Sonal Singh, M.D., M.P.H., lead author on the study from Johns Hopkins University Medical Center. "They don't need Chantix to quit and this is another reason to consider avoiding Chantix altogether."

In the paper, the researchers wrote 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."

"The sum of all serious adverse effects of Chantix clearly outweigh the most positive effect of the drug in my view," Furberg said. "The time has come for the FDA to withdraw the drug from the market."

Along with Furberg and Singh, co-authors on the study, funded by the National Center for Research Resources and the National Institutes of Health Roadmap for Medical Research, are: John Spangler, M.D., of Wake Forest Baptist, and Yoon K. Loke, M.D., MBBS, of the University of East Anglia.