EAGLES- A Randomized Clinical Trial Showing No Evidence of Smoking Cessation Treatments Association with MACE

Iqra Qamar, M.D.
By Iqra Qamar, M.D. on

EAGLES (Evaluating Adverse Events in a Global Smoking Cessation Study), a randomized clinical trial, published in the Journal of the American Medical Association, provides evidence that smoking cessation medications do not increase the risk of serious cardiovascular events in the general population of smokers.

When asked about the consensus of the evidence in regard to the cardiovascular safety risk of smoking cessation treatments, Dr. Benowitz, Professor of Medicine at University of California San Francisco, who is the first author of this study, said, “Prior to this study most of the data suggested that smoking cessation medications were safe, even for patients with cardiovascular disease; and certainly safer than cigarette smoking. There had been some concerns about adverse CV effects of varenicline, bupropion and Nicotine replacement therapy (NRT), based mostly on case reports and one meta-analysis showing increased palpitations and arrhythmia for  nicotine patch, and one small analysis showing increased delayed risk for varenicline.”

Despite the proven efficacy of smoking cessation medications, many clinicians have been reluctant while prescribing them because of concerns regarding their cardiovascular safety. This study was done to evaluate the relative cardiovascular safety of smoking cessation medications comparing Varenicline (1 mg BID), Bupropion (150 mg BID), NRT (21-mg/d patch with tapering), and placebo.

“Our study is the largest study by far and the only prospective study to compare all smoking cessation medications with placebo. We find no evidence of cardiovascular harm in the general population of smokers.” Dr. Neal L Benowitz MD.

 

It was a multinational, double-blind, triple-dummy, placebo and active-controlled trial (EAGLES) with its non-treatment extension trial that was conducted at almost 140 multinational centers. Participants included smokers who received at least 1 dose of study medication (n = 8058), as well as a subset of those who completed 12 weeks of treatment plus 12 weeks of follow up and agreed to be followed up for an additional 28 weeks (n = 4595).

The primary endpoint was the time to development of a major adverse cardiovascular event (MACE), such as cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke during treatment. Secondary endpoints included the occurrence of MACE and other pertinent cardiovascular events (MACE+), such as new-onset or worsening peripheral vascular disease requiring intervention, coronary revascularization, or hospitalization for unstable angina).

EAGLES and its extension trial findings showed that the incidence of MACE during treatment and follow-up was low and did not differ significantly by treatment. There were no significant treatment differences noticed in terms of cardiovascular events, blood pressure, or heart rate.

Regarding the impact of these findings on the clinical practice, Dr. Benowitz commented, “We hope that clinicians will be reassured that smoking cessation medications are safe, and offer smoking cessation medications to all smokers seen in clinical practices.”

Source: Cardiovascular Safety of Varenicline, Bupropion, and Nicotine Patch in Smokers, April 9, 2018. doi:10.1001/jamainternmed.2018.0397

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