A popular drug prescribed to help people quit smoking may pose a significantly increased risk of heart attack in users, a new study finds. The results may further complicate doctors’ and patients’ decisions to use the drug, Chantix, which has been associated with various safety concerns since its approval in 2006.
The new paper, an analysis of data from 14 previous studies involving Chantix (varenicline), found that smokers and smokeless tobacco users taking the drug experienced a 72% increased risk of a serious heart event within a year.
“The magnitude of the risk did surprise us,” says Sonal Singh, a professor of medicine at Johns Hopkins University School of Medicine and one of the study’s co-authors.
Shortly before the July 4 release of the paper by the Canadian Medical Association Journal (CMAJ), the U.S. Food and Drug Administration (FDA) issued a safety announcement warning users that Chantix, while helping smokers quit for as long as a year, was associated with a “small, increased risk of certain cardiovascular adverse events in patients who have heart disease.”
That announcement was based on the findings of a randomized trial of 700 smokers with diagnosed cardiovascular disease who took either Chantix or placebo for three months. The data have prompted the FDA to include a warning on the drug’s label.
The CMAJ analysis included the study on which the FDA based its safety announcement. But most of the other participants included in the CMAJ study were healthy and did not have heart problems and still showed a similar spike in cardiac events.
The results may pose a quandary for many smokers who attempt to give up cigarettes each year — about half of the 46 million current smokers in the U.S. — as well as the doctors who advise them. Should people try to quit smoking with Chantix, or will using the drug increase their risk of heart disease just as much as, or even more than, smoking itself?
This is not the first time that harmful side effects have been associated with Chantix. According to the Institute for Safe Medication Practices (ISMP), a nonprofit organization that educates the public about drug safety, numerous reports of adverse effects from Chantix have been reported to the FDA since the drug was approved five years ago. In the final months of 2007, for instance, varenicline accounted for more occurrences of serious injury than any other drug, according to the FDA’s adverse events reports. These side effects included irregular heartbeat, seizures and blackout, as well as more serious psychiatric effects including aggression and suicide.
In 2008, when the ISMP published a compilation of its findings on Chantix’s potential harms, the drug’s psychiatric risks caught the attention of the FDA. The agency immediately ordered pilots with the Federal Aviation Administration to stop taking the drug; soon after, the Federal Motor Carrier Safety Administration, which oversees the trucking and bus industry, issued a similar ban for its commercial drivers. The Department of Defense followed suit and prohibited certain weapons and aircraft personnel from using the smoking cessation drug as well.
In 2009 the FDA gave the drug its most restrictive black box warning because of “serious neuropsychiatric events” including suicidal behavior.
The FDA says that it wasn’t aware of any potential heart risks until 2010, when Pfizer, which manufactures Chantix, conducted a study of the drug in heart patients to see whether it was as effective at reducing tobacco use in high-risk smokers as in those without heart trouble. When the company provided its results to the FDA, agency officials paid particular attention to any indication of heart problems. “We did a careful assessment of endpoints, exactly because it was a population of patients with known heart disease,” says Sandra Kweder, deputy director of the Office of New Drugs at the FDA. “That was where we saw the first signal that was particularly concerning, and led us to issue the safety communication.”
The agency acknowledges, however, that there may have been hints of heart issues in the original data that Pfizer submitted to win approval for Chantix in 2006. “When the application came in, we did notice a difference in cardiovascular events [between varenicline users and control subjects] just based on rough counts,” says Curtis Rosebraugh, director of the Office of Drug Evaluation II at the FDA. “What we typically do when we see an imbalance is assign viewers to look at the individual patient data to make sure things were coded correctly. We did that, and one reviewer said the imbalance was not as big as what the original data showed, and the other reviewer said that the difference actually favored Chantix. When we see things like that, that’s not a clear signal to us. That’s why things [such as a warning] weren’t put on the label.”
Singh takes issue with that decision, noting that if Pfizer and the FDA had noted the potential heart risks earlier, proper studies might have been done to investigate whether some people were more likely to develop heart problems than others on Chantix, potentially sparing many patients further harm. “What’s missing here is that this information was present with Pfizer in 2006,” says Singh. “Why wasn’t that presented on the original label? Why wasn’t this information given then? Why wasn’t I as a provider given that information in 2006? That’s what I’m mad about.”
Pfizer maintains that the drug is safe, and notes limitations in Singh’s analysis, including the small absolute number of heart events associated with Chantix. “The actual difference in cardiovascular event rates seen in the Singh analysis was less than one quarter of one percent (i.e., 1.06% with varenicline versus 0.82% with placebo),” Dr. Gail Cawkwell, vice president of medical affairs at Pfizer said in a statement. “The health benefits of quitting smoking are immediate and substantial.”
That’s something about which everyone can agree. The question is, how does the risk of continuing to smoke stack up against the risk of heart problems with varenicline? The currently available data aren’t sufficient to answer that question, so the FDA is asking the company to conduct its own study of all existing data on varenicline and heart issues among users.
In the meantime, some experts are turning to other smoking cessation options to help their patients quit. “Try the nicotine patch, try bupropion, try everything you can, and if you really can’t quit, and if you don’t have a lot of heart disease risk, then try varenicline,” says Dr. Steven Nissen, department chair of cardiovascular medicine at the Cleveland Clinic. “But I have to be careful in also telling people that I can’t tell you with absolute certainty that it’s safe.”
Quitting cigarettes, however, is always safer than continuing to smoke. It’s just a matter of weighing the risks of the way you decide to kick the habit.