Pharmacological Smoking Cessation Aides And Cardiovascular Safety

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.


  1. 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.
  2. 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.
  3. 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 Parikh Headshot

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.


It’s Electric!

As this crowd knows, cardiovascular disease is the leading cause of death worldwide, and though we’ve made great advancements to reduce morbidity and mortality in these patients, there is a desperate search for innovative new treatment strategies.
Traditionally, most chronic conditions are addressed with small molecule-based drugs that bind to their molecular target, exert downstream effects, and bring about therapeutic benefits. In severe cases, a visit to the operating room may be warranted in addition to a pharmacological treatment. For a heart attack, stenting and timely reperfusion remains the preferred emergency intervention.
Drugs and surgeries, though lifesaving and indispensable, are associated with off-target effects, invasive operations, and other negative complications. The ideal therapy would maximize positive patient outcomes and minimize any associated unpleasantries.
Electroceuticals, also known as bioelectronics, are a radical new approach to medical treatment that harness the power of electricity to safely and precisely treat an array of conditions, from sleep apnea to Parkinson’s disease. These are tiny devices that can be implanted in a patient to survey or modify nerve signaling in her body. The most familiar electroceuticals in clinical practice include defibrillators and pacemakers, but recent advances such as vagus nerve and spinal cord stimulation indicate that there is great potential for this field to be explored, expanded, and refined for cardiovascular disease applications.
A spark of interest is growing in the eyes of several industry leaders, and some have already devoted resources to the development and commercialization of bioelectronics medicines. Galvani Bioelectronics, the daughter company of GlaxoSmithKline and Alphabet’s Verily Life Science, is one such investment in the advancement of electronic medicine.
Basic scientists like me have much curiosity and some concerns. Among them, the neurobiology and molecular mechanisms of how electroceuticals elicit their effects are relatively unexplored in some fields.  Such challenges call on an interdisciplinary community of expert scientists, engineers, and clinicians to focus their talents and push for solutions. Hopefully we will all be shocked (in a good way!) by the disruptive technologies this field will bring us in the future.

You can read further about Electroceuticals Spark Interest here.

Annie Roessler Headshot

Annie Roessler is a PhD Candidate at Loyola University in Chicago, IL. Her research focuses on the neurobiology and molecular mechanisms of electrically-induced cardioprotection. She tweets @ThePilotStudy and blogs at flaskhalffull.com