British and American scientists analysed 14 clinical trials of Champix, sold as Chantix in the United States and known generically as varenicline, and found the likelihood of developing serious heart problems resulting in hospitalisation, disability or death was 72 percent higher in patients taking the drug compared with those taking a placebo.
The researchers said U.S. drug regulators, who have already issued warnings about Chantix's safety in certain patient groups, should take note of their findings.
"Our new research shifts the risk-benefit profile of varenicline," said Sonal Singh of Johns Hopkins University School of Medicine, who led the research and published it in the Canadian Medical Association Journal.
"People should be concerned. They do not need Chantix to quit and this is another reason to consider avoiding Chantix altogether," he said in a statement. "People want to quit smoking to reduce the risk of cardiovascular disease, but in this case they are taking a drug that increases the risk for the very problems they are trying to avoid."
Pfizer, the world's largest drugmaker, said in a statement it disagreed with Singh's interpretation of the data. "The analysis contains several limitations -- most notably that it is based on a small number of events, which raises concerns about the reliability of the authors' conclusions."
Investors had high hopes for Chantix when Pfizer launched it in 2006. But reports of suicidal thoughts and other mental health problems in users led U.S. Food and Drug Administration (FDA) officials to order a so-called "black box" warning on the drug's label in 2009.
Chantix, which reduces both the craving for and pleasurable effects of cigarettes, is used by heavy smokers who find it difficult to quit. It is one of the biggest-selling stop-smoking drugs in the United States, and has more than 70,000 prescriptions every month in Britain. Annual sales of around $800 million make Chantix a moderate-sized product for Pfizer.
LIFE-THREATENING
In the study, Singh's team reviewed and analysed 14 trials involving more than 8,200 healthy people given either Champix or a placebo -- a dummy pill.
Whereas the number of people who died in each group was the same, at seven, the increased risk of a major harmful cardiovascular event requiring hospitalisation was 72 percent among those taking Champix/Chantix. 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.
Yoon Loke of Britain's University of East Anglia, who co-led the research, said while the number of serious heart problems was low, at around 1 percent, it was worth noting that most of the studies were carried out in healthy people.
"These are life-threatening diseases and so any increased risk should be carefully avoided -- particularly as heavy smokers are already susceptible to cardiovascular disease," Loke said in a statement.
He said the results suggested that in smokers who do have a history of heart disease, an estimated 1-in-28 would experience extra heart problems if they used Champix for a year.
Smoking, which kills up to half of those with the habit, has been predicted to claim up to 8 million lives a year by 2030 if current trends persist.
It causes lung cancer, which is often fatal, and other chronic respiratory diseases, and is also a major risk factor for cardiovascular diseases -- the world's number one killers.
The FDA said last month it was changing the Chantix label to make clear it carried an increased heart risk for people who already have cardiovascular disease.
In May, France said it was removing Champix from a register of reimbursable treatments on state social security funds after questions were raised about the drug.
Pfizer said it works with regulators a continual basis to review and monitor data for Chantix.
"In particular, we are working with FDA to conduct a combined analysis of clinical trial data (meta-analysis), which will help further evaluate the cardiovascular safety of Chantix," the drugmaker said. (Reporting by Kate Kelland; Editing by Sophie Walker and Dan Lalor)