Smoking Cessation Pharmacotherapies Are Not Hazardous to Heart
Abstract
Varenicline, bupropion, and the nicotine patch pose no more risks of heart attacks, strokes, or other major cardiovascular complications than placebo, even among smokers with psychiatric illness.
The single biggest step smokers can take to reduce their risks of serious health risks and premature death is to quit. Most guidelines agree that the best approach to quitting is counseling coupled with pharmacotherapy such as varenicline, bupropion, or nicotine replacement. Despite the proven efficacy of smoking cessation medications, however, some clinicians remain hesitant to prescribe them due to concerns over possible side effects of the medications, including cardiovascular safety.
A study published April 9 in JAMA Internal Medicine concluded that relative to placebo, smoking cessation medications pose no risk of serious cardiovascular events in most smokers, including those who have a psychiatric disorder.
These findings are the latest to come from the Evaluating Adverse Events in a Global Smoking Cessation Study (EAGLES)—a large clinical trial that enrolled over 8,000 smokers from 140 clinical centers across the world. The trial was initially designed to assess the potential risk of psychiatric side effects in smokers taking varenicline or bupropion (and as reported in 2016, these medications posed no increased neuropsychiatric risks). The study was later extended so the investigators could monitor long-term cardiovascular risks as well.
As lead EAGLES investigator Neal Benowitz, M.D., a professor of medicine at the University of California, San Francisco, explained, the cardiovascular concerns over varenicline and bupropion stem from their mechanisms of action. Varenicline binds to nicotine receptors that stimulate blood flow; bupropion is an amphetamine-like compound that can increase blood pressure and heart rate.
No formal studies had identified any cardiovascular problems with these cessation medications, but the anecdotal evidence was enough that drug regulatory agencies in the United States and Europe requested that the manufacturers of varenicline (Pfizer) and bupropion (GlaxoSmithKline) conduct a large study that hopefully would provide some definitive answers.
The 8,058 EAGLES participants (including 4,116 with a psychiatric disorder) were randomly assigned to receive either varenicline (1 mg twice daily), bupropion (150 mg twice daily), a nicotine patch (an active control group), or placebo pills (passive control) for 12 weeks. The participants were then followed for an additional 40 weeks.
About 4,600 participants remained enrolled in the study at the end of the 52 weeks; of these, 26 participants experienced a major cardiovascular event (defined as a heart-related death, nonfatal heart attack, or nonfatal stroke), and 21 others had some cardiovascular complication such as peripheral cardiovascular disease or the need for bypass surgery.
There were no differences in the frequency of a cardiovascular event among any of the four treatment groups, nor was there any indication that adverse outcomes were more frequent in participants with a psychiatric disorder.
Benowitz acknowledged that since the total number of cardiovascular events was so small, a very slight cardiovascular risk in one of the treatments might go unnoticed. Even if that were the case, though, that risk would be far outweighed by all the health benefits of smoking cessation, he said.
“We hope that this study will reassure physicians that if a smoker comes into their clinic looking to quit, medication-assisted therapy is still the recommended approach,” he said.
One caveat of the study Benowitz noted is that none of the participants had any unstable cardiovascular or psychiatric problems, such as uncontrolled blood pressure, a recent heart attack, or an active substance use disorder (other than smoking). These populations would require some special considerations. Bupropion, for example, should be avoided in people with a history or risk of seizures, eating disorders, or unstable blood pressure, while varenicline is cleared by the kidneys and should not be used in people with kidney disease.
As noted above, EAGLES was funded by Pfizer and GlaxoSmithKline, at the behest of the Food and Drug Administration and European Medicines Agency. ■
“Cardiovascular Safety of Varenicline, Bupropion, and Nicotine Patch in Smokers: A Randomized Clinical Trial” can be accessed here.
