A new study led by a Johns Hopkins researcher says the popular anti-smoking drug Chantix significantly increases the risk for a heart attack or other serious heart problem in healthy, middle-aged smokers.
Dr. Sonal Singh, the study's lead author, is calling for warnings on the drug to be stronger than those currently required by the Food and Drug Administration.
"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," said Singh, an assistant professor of general internal medicine. The study, which said the risk increased by 72 percent for healthy, middle-aged smokers, was released Monday in the Canadian Medical Association Journal.
Singh, who reviewed 14 clinical trials, said the risk is significantly higher than the U.S. FDA indicated in mid-June when it warned about a small increase in cardiovascular impacts for those on the drug, generically known as varenicline. The FDA's warning was based on a study of 700 smokers who already had cardiovascular disease.
FDA officials responded by saying that more analysis was needed before the agency would change its position. They have also asked the drug's maker, Pfizer, to conduct another review and to plan its own study.
The FDA also has asked Pfizer to conduct a large, randomized study of possible psychiatric effects. Reports of depression and suicidal thoughts led two years ago to a boxed warning on the drug's label, its most serious type.
"The recent [Hopkins] analysis is consistent with a concern we have already identified," wrote FDA spokesman Jeff Ventura in an email response to questions about the study.
In the meantime, the FDA cited studies that found Chantix was effective in helping patients quit smoking for as long as a year.
Pfizer said in a statement that the company "strongly believes in and supports Chantix as an important treatment option" and that it disagrees with the interpretation of the data put forth by Singh's study. "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," the release said. "The authors acknowledge that their risk 'estimates are imprecise owing to the low event rates.'"
For Carolyn Miller, it's been four years since she quit with the help of Chantix. The echocardiography technician in the cardiology department at Bon Secours Hospital in Baltimore said she'd tried many times over 32 years to kick the habit using nicotine patches and going to smoking cessation meetings.
Once on Chantix, it wasn't even a week before Miller, 55, lost her desire to smoke. When the cravings ended, she stopped taking the drug and has had no cardiac issues.
"The key was being mentally ready," she said. "But I really think the Chantix worked. I still don't have cravings."
The FDA says Chantix works by blocking the effects of nicotine in the brain, and eases withdrawal symptoms. It also blocks the effects of nicotine from cigarettes if users resume smoking.
Miller said she is breathing and sleeping better, food tastes better, and she has more energy. But she never would have taken Chantix if she'd known about the FDA warning and Hopkins research, she said.
She plans to stop recommending it to her heart patients. "A 70 percent increase in risk is scary," she said.
Jordan Buescher isn't as sure what he would have done with the information in the Hopkins study. The 33-year-old probation officer for the state of Michigan took Chantix for months to kick his 15-year cigarette habit.
A friend who worked for a cancer awareness group had persuaded him to undertake a complete makeover, from diet to exercise to smoking. He relied on support from friends and family, ran a half marathon and has been off cigarettes for a year.
He knew that he might have psychological problems from Chantix, and indeed, he had extreme mood swings that sent him to a psychologist and made him hard to be around. But he thought his health was worth the trouble.
"If someone said there is a one in two chance you're going to die, you wouldn't take [a drug]," he said. "But sometimes you have to take some risks to live a better life. Maybe that's easy for me to say because I didn't have a heart attack and die."
Knowing about potential risks now, he said, he probably would have done more research, consulted more doctors and tried means of quitting that didn't involve the "wonder drug" first.
Others might also be seeking alternatives, despite such testimonials about effectiveness. Pfizer reported revenue of $199 million in the first quarter of the year from Chantix, up 5 percent, largely because of international sales. But the company said sales were tempered by labeling in the United States. France also has stopped covering the drug, called Champix in Europe, under its public insurance.
Pfizer says doctors have written 7 million prescriptions for Chantix in the United States and 13 million worldwide since it was approved in 2006. It had a shortened review period because the FDA said it had shown a significant improvement over available therapy.
Singh said he and colleagues from Wake Forest University School of Medicine and the University of East Anglia in the United Kingdom decided to take a closer look at Chantix when one of the doctors reported patients with chest pains.
With a grant from the National Institutes of Health's National Center for Research Resources and the NIH Roadmap for Medical Research, they reviewed 14 clinical trials involving 8,200 healthy people who took Chantix or a placebo. Singh said the extent of the risk for heart attacks and arrhythmias wasn't apparent until all the data were reviewed at once.
There weren't a large number of deaths, according to the study, but the risk for those without heart disease having a cardiac event that required hospitalization was 72 percent higher than for those taking a placebo. The average age of study participants was less than 45.
Singh estimated there have been 62,000 serious cardiac events in the United States from the drug. He now emphasizes the need to quit smoking, but without Chantix.
The FDA says smoking kills 1,200 people a day. The American Heart Association calls it the most preventable cause of premature death in the country. It can lead to several chronic diseases including cancer, lung problems and coronary artery disease.
The association supports both drugs and counseling to help tobacco users quit, as does the U.S. Preventive Services Task Force, an independent panel of prevention experts. Approved drugs include over-the-counter nicotine patches, gum and lozenges, and a prescription nicotine-replacement product, Nicotrol.
Chantix and Zyban, or bupropion, are non-nicotine, prescription pills. Zyban also carries an FDA warning about possible psychiatric problems.
"Combination therapy with counseling and medications is more effective than either component alone," the task force recommendation reads.
As part of the campaign against smoking, the federal government is turning to new graphic packaging on cigarettes. And states such as Maryland are maintaining free phone lines.
The state established the Tobacco Quitline, 1-800-QUIT-NOW, in 2006 and also offers free nicotine replacement therapy to callers who register for counseling, said Dawn S. Berkowitz, chief of the state's division of federal and special tobacco control initiatives.
The state reports the percentage of residents who smoke dropped to 15.2 percent in 2010 from 20.5 percent in 2000, and among high school students, the rate dropped to 14.1 percent in 2010 from 23 percent in 2000.
Singh said he encourages his patients to quit through counseling and maybe nicotine patches. He plans to continue lobbying the FDA to increase the warnings for, and insurance companies to no longer fund, Chantix.
"Patients ask for Chantix because the ads are all over TV," he said. "If they say they want to quit smoking, I'll spend time and counsel them. … There are too many consequences from this drug."