Healthy, middle-aged smokers who take the most popular smoking cessation drug on the market have a 72 percent increased risk of being hospitalized with a myocardial infarction (MI) or other serious heart problems compared to those taking a placebo, a Johns Hopkins-led study suggests.

"People want to quit smoking to reduce the risk of cardiovascular disease but in this case they're taking a drug that increases the risk for the very problems they're trying to avoid," says Sonal Singh, M.D., M.P.H., an assistant professor of general internal medicine at the Johns Hopkins University School of Medicine and the lead author of the research.

In the study, described in the Canadian Medical Association Journal, Singh and his colleagues reviewed and analyzed 14 double blind, randomized, controlled clinical trials involving more than 8,200 healthy people who received either varenicline or a placebo. Whereas the number of people who died in each group was the same (seven), the increased risk of a major harmful cardiovascular event requiring hospitalization such as an MI or arrhythmia was 72 percent in the varenicline arms. None of the studies followed people for longer than a year. The average age of study participants was less than 45 years and the majority were men.

Varenicline has been shown to modestly increase the chances of a successful quit attempt, compared to unassisted smoking cessation attempts. But overall, the majority of smokers who quit do so without any pharmaceutical assistance at all.

Moreover, Singh noted, varenicline already carries a boxed warning - the Food and Drug Administration's highest level of caution - because of its association with suicidal thoughts and behaviors. "We notified the FDA of our cardiovascular safety concerns with Chantix earlier this year," Singh says.

On June 16, the FDA announced that on the basis of a 700-person study, people with existing heart disease who use varenicline have a slightly increased risk of an MI or other cardiovascular event. But Singh's study found that varenicline substantially increased the risk of a serious cardiovascular event even among smokers without heart disease. "I think our new research shifts the risk-benefit profile of varenicline," Singh says. "People should be concerned. They don't need varenicline to quit and this is another reason to consider avoiding varenicline altogether."

Smoking has long been associated with increased risk of cardiovascular disease and cardiac death and quitting is known to reduce those risks. Singh and his colleagues from Wake Forest University School of Medicine and the University of East Anglia in the United Kingdom emphasize the need to quit smoking, but suggest that varenicline may not be the right drug to kick the habit.

Singh's research was funded by a grant from the National Center for Research Resources and the National Institutes of Health Roadmap for Medical Research.