Pharmacological smoking cessation therapies have had their challenges. For example, varenicline previously had a US Food and Drug Administration black box warning regarding neuropsychiatric risks.
The EAGLES study, published 2016, was an industry sponsored, randomized, placebo-controlled trial of nicotine, varenicline, and bupropion that sought to address the neuropsychiatric risk profile of these medications.1 They randomized participants with and without known psychiatric comorbidities to these medications and found that these agents were not associated with an increased risk of neuropsychiatric adverse events. Further, the study found varenicline to be more effective than nicotine, bupropion, and placebo for smoking cessation.
The FDA black box warning for varenicline was removed. However, concerns regarding the cardiovascular safety persisted. Apart from abundant observational data on this topic, there have been several randomized trials as well. For example, in 2015, a randomized clinical trial of varenicline versus placebo for patients hospitalized with acute coronary syndrome demonstrated efficacy for cessation and did not raise a safety signal.2
Further, a secondary analysis of the EAGLES study regarding cardiovascular safety was recently published.3 They compared rates of major adverse cardiovascular events, and changes in blood pressure and heart rate, among participants randomized to placebo, varenicline, bupropion, and nicotine replacement. They found very low rates of major cardiovascular events and did not find differences between drugs. Of course, these were not patients with recent or significant cardiovascular comorbidities, so the results do not generalize beyond the general population of smokers.
There is thus mounting evidence for both the psychiatric and cardiovascular safety of pharmacological smoking cessation therapies. While it can be argued that an adequately powered safety trial in patients in acute and/or significant cardiovascular disease has yet to be performed, it may nonetheless be time to create gold standard cessation programs for patients with cardiovascular disease. It may be premature, however, to do the same for patients with cerebrovascular disease – more evidence may be needed.
- Anthenelli RM, Benowitz NL, West R, et al. Neuropsychiatric safety and efficacy of varenicline, bupropion, and nicotine patch in smokers with and without psychiatric disorders (EAGLES): a double-blind, randomised, placebo-controlled clinical trial. Lancet. 2016:387;2507-2520.
- Eisenberg MJ, Windle SB, Roy N, et al. Varenicline for Smoking Cessation in Hospitalized Patients With Acute Coronary Syndrome. Circulation. 2015:137; https://doi.org/10.1161/CIRCULATIONAHA.115.019634.
- Benowitz NL, Pipe A, West R, et al. Cardiovascular Safety of Varenicline, Bupropion, and Nicotine Patch in SmokersA Randomized Clinical Trial. JAMA Internal Medicine. 2018; doi:10.1001/jamainternmed.2018.0397.
Neal S. Parikh, MD, earned his MD from Weill Cornell Medical College and completed residency training in neurology at the same institution. He is now an NIH T32 neuro-epidemiology and vascular neurology fellow at New York-Presbyterian Hospital/Columbia University Medical Center. He tweets @NealSParikhMD and contributes to Blogging Stroke as a blogger.