among stable adult smokers with up to one year of follow-up.
“In what we believe to be the largest smoking cessation clinical trial and the only trial comparing NRT, bupropion, and varenicline [with] placebo, we found no signal that smoking cessation pharmacotherapy increases the risk of serious cardiovascular disease or cardiovascular adverse events in a general population of smokers,” concluded Neal L. Benowitz, MD, of the University of California, San Francisco, and his associates. “While the number of events was small, the incidence of serious cardiovascular events was low, suggesting that any absolute increase in risk that we might have missed would be low and not clinically meaningful.” The findings were reported online April 9 in JAMA Internal Medicine.
In this double-blind, multicenter, triple-dummy trial (EAGLES), Dr. Benowitz and his associates randomly assigned 8,058 adult smokers, who did not have acute or unstable cardiovascular disease, to receive bupropion (150 mg twice daily), varenicline (1 mg twice daily), NRT (21-mg/day patch with tapering), or placebo for 12 weeks, followed by 12 weeks of follow-up. A total of 4,595 patients agreed to be followed for another 28 weeks during an extension phase of the trial. More than half of the patients were women and the average age of a participant was 47 years. The primary endpoint was time to major adverse cardiovascular event (MACE), including cardiovascular death, nonfatal myocardial infarction, and nonfatal stroke. The researchers selected time to MACE as their primary endpoint to better detect differences among groups. One of the secondary end points was the occurrence of MACEs over the same 3 time intervals. Additionally, cardiovascular deaths, nonfatal MI, and nonfatal stroke (the components of MACE) were evaluated individually, as were hospitalizations for congestive heart failure and serious arrhythmias.
Differences in time to onset of MACE between all four patient groups, were not significant. The overall incidence of MACEs was less than 0.5% during all observation periods. There were also no significant differences in rates of the individual types of MACE, coronary revascularization, hospitalization for unstable angina, or new or worsening peripheral vascular disease requiring treatment among groups. Changes in body weight, blood pressure, and heart rate also were similar across patients.
There were five cardiovascular deaths, including one in the varenicline group, two in the bupropion group and two in the placebo group, according to the researchers. Overall the trial results “are consistent with and support previously published findings from meta-analyses and small clinical trials in smokers with known [cardiovascular disease],” they wrote.
GlaxoSmithKline and Pfizer, who make and market smoking cessation therapies, sponsored the study. Dr. Benowitz disclosed a consulting relationship with Pfizer and other pharmaceutical companies. He also has been a paid expert witness in litigation against tobacco companies. Eight coinvestigators disclosed ties to Pfizer, GlaxoSmithKline, and other companies.
SOURCE: Benowitz NL et al. JAMA Intern Med. 2018 Apr 9. doi: 10.1001/jamainternmed.2018.0397)