July 4, 2011 -- On the heels of the FDA's admission that Chantix, Pfizer's smoking cessation drug, may aggravate heart problems in those with cardiovascular disease, new research suggests that they're not the only ones at risk. Chantix may increase the risk of heart attack and other adverse events for those with a clean bill of cardiovascular health.
Though concerns over Chantix' effect on the heart were raised during the drug's approval process in 2006, the FDA's recent move to include a cardiovascular warning in the drug's safety information marks the first time the organization has publicly discussed such potential risks. It's a move that is a long time coming for Dr. John Spangler, co-author on the new research, a meta-analysis published Monday in the Canadian Medical Association Journal.
Since 2007, Spangler, director of Tobacco Intervention Programs at the Wake Forest University School of Medicine in Winston-Salem, N.C., has been attempting to get the word out concerning possible cardiac and other safety concerns for those taking Chantix, but his prescient warnings were largely ignored until recently.
"I had spoken to JAMA and LANCET and people from Pfizer, and emailed the FDA, and no one was very interested or concerned about the things I was finding," Spangler says.
Spangler's meta-analysis, done with lead author Dr. Sonal Singh, an assistant professor of general internal medicine at the Johns Hopkins University School of Medicine, could stir concern too loud to be pushed aside, however, especially in light of the FDA's reconsideration of Chantix's safety profile.
Study authors looked at 14 past studies of Chantix and found that overall, people on the drug had a 72 percent increased risk of being hospitalized with a heart attack or other serious heart problems when compared with those taking a placebo.
"In the proportion of smokers that had never had heart disease, we saw an even greater risk of adverse events, about 150 percent increased risk," says Singh.
"The main goal of smoking cessation is to reduce the risk of heart attack that comes with being a smoker, but this drug is doing the exact opposite. It's increasing the risk of what they're trying to avoid," Singh says.
The most "frustrating" part, he adds, is that the Food and Drug Administration found an increased risk for cardiac events back in 2006, "but they did not warn patients or physicians at that time that it may be a risk. They didn't put it on the label," Singh says.
According to the FDA, however, the data Singh refers to was too inconsistent to warrant a label mention -- until recent studies suggested it might be true.
Chantix Safety Concerns Persist
Spangler alerted the FDA to potential safety concerns back in 2007 when he discovered that a small study widely quoted as showing that Chantix was safe to use for up to a year was in fact misleading. When he ran the numbers the authors reported, he found that those on Chantix for a year had 2.5 times the risk of serious adverse events, including cardiovascular events, as those on placebo.
In the five years since Chantix was approved, it has been the subject of several FDA safety reviews, most notably one concerning depression, suicidal thoughts and suicidal actions -- adverse effects that earned Chantix the FDA's strongest "black box" warning label in 2009.
It wasn't until earlier this month, however, that the FDA publicly acknowledged a potential link between Chantix and cardiovascular issues after reviewing a 2010 study led by Dr. Nancy Rigotti, a professor at Harvard Medical School and the director of Mass General's Tobacco Research and Treatment Unit, which looked at cardiovascular risk and Chantix.
The FDA contends that the Rigotti study was the first to raise significant concern over cardiac risk, as the other studies showed negative cardiac effects on Chantrix that were "fragile" and "not something we would label on," says Curtis Rosebraugh, director of the Office of Drug Evaluation II at the FDA.
Smoking Cessation Safety -- Is Chantix Worth It?
Pfizer said in a statement to ABC News that it disagrees with Singh et al's interpretation of the data, arguing that the actual number of heart attacks and other cardiac events were too small to determine if Chantix was the cause.
Because of the FDA's plans to amend the label information, however, the agency has already asked the pharmaceutical company to turn over all its data concerning Chantix and adverse cardiac events so that the FDA can perform its own in-depth analysis of the drug's safety profile. That profile will use, among other sources, the 14 studies evaluated in Singh's meta-analysis.
"Had we not already been working on our own analysis, Singh's analysis would have raised concerns. As it is, it underscored our own concerns," says Celia Winchell, medical team leader of addictive products at the FDA.
Smokescreen -- FDA Only Now Reconsiders Chantix Heart Safety
Singh et al. pooled the data from 14 previous studies, including 8,200 patients in total. Though the Rigotti study, which looked at those with cardiovascular disease, was included in their meta-analysis, the vast majority of patients included in their research did not have cardiovascular disease.
Despite the relatively heart-healthy makeup of their study population, an increased risk in heart attack, stroke and other serious heart complications was still associated among those taking the drug. The effect was so strong that many experts in cardiology and smoking cessation feel heightened caution and limited, if not discontinued, use of Chantix is justified.
"The data … justify a black box warning on Chantix labeling about the cardiovascular risk," says Dr. Jay Cohn, director of the Rasmussen Center for Cardiovascular Disease Prevention at the University of Minnesota Medical School.
"It may be justified to accept the small increase in absolute risk [of adverse cardiac events], to gain the long-term benefit of smoking cessation … in certain individuals," she says.
For some clinicians, the psychological risks combined with the potential cardiovascular risks are enough to stay away from Chantix altogether. Spangler hasn't prescribed it in years and Daniel Seidman, director of the Smoking Cessation Services at Columbia University Medical Center, says he has "avoided Chantix in my clinical work with smokers precisely because of safety concerns. This [study] is yet another black eye for Chantix."
Combining nicotine replacement, such as the gum and the patch or lozenge, has been shown to be more effective for quitting anyway, he adds.
Singh takes it a step further, calling for the FDA to withdraw Chantix from the market altogether. Most importantly, however, he wants patients and doctors to be aware of all the risks that may go along with using the drug.
"These results are very concerning. Unfortunately, this was concerning five years ago. We can't wait another five years to tell smokers that they might be at risk for heart problems when on Chantix," says Singh.
Sales of Chantix totaled $755 million last year. Thirteen million people worldwide have been prescribed Chantix.