Quit-Smoking Drug Not Associated with Heart Disease, Depression

Clinicians may be able to prescribe varenicline more broadly to help more smokers quit.
Clinicians may be able to prescribe varenicline more broadly to help more smokers quit.
The effective quit-smoking drug varenicline has been prescribed with FDA warnings of heart disease and depression, but recent research has found no evidence of elevated risk.

A drug that helps smokers quit was not associated with an elevated risk of heart disease or depression, as was previously believed, findings from a large retrospective cohort study indicate.

The quit-smoking drug varenicline (Chantix, Pfizer) was approved by the US Food and Drug Administration (FDA) and European Medicines Agency (EMA) in 2006, and has subsequently been recommended in US and international clinical guidelines. Findings from previous studies have shown varenicline to be more effective than bupropion as well as single forms of nicotine replacement treatment (NRT) such as patches, gum, or lozenges.

However, subsequent reports raised concerns about the risk of serious cardiovascular and neuropsychiatric events with varenicline. After authors of a meta-analysis reported an increased risk of cardiovascular events associated with varenicline, the FDA and EMA issued warnings about “changes of behavior, agitation, depressed mood, suicidal ideation, and attempted and completed suicides” among varenicline users despite major study limitations. Later analyses found no significant association between varenicline and cardiac or neurologic problems.

Daniel Kotz, PhD, of the Institute of General Practice and Medical Faculty at the Heinrich-Heine-University in Düsseldorf, Germany, and colleagues sought to better understand whether varenicline is truly associated with such risks.

The researchers identified 164,766 patients from the QResearch database (which holds records for more than 13 million patients across England) who were prescribed an NRT, bupropion, or varenicline to aid in smoking cessation. They then analyzed associations between NRT, bupropion, and varenicline users and neuropsychiatric and cardiovascular events.

No evidence was found of any increased risk of cardiovascular or neuropsychiatric adverse events in smokers using varenicline or bupropion when compared with NRT users (all hazard ratios <1). On the contrary, varenicline was actually associated with a significantly reduced risk of ischemic heart disease (HR 0.80; 95% CI: 0.72-0.97), cerebral infarction (HR 0.62; 95% CI: 0.52-0.69), heart failure (HR 0.61; 95% CI: 0.45-0.83), arrhythmia (HR 0.73; 95% CI: 0.60-0.88), depression (HR 0.66; 95% CI: 0.63-0.69), and self-harm (HR 0.56; 95% CI: 0.46-0.68).

With cigarette smoking continuing to be one of the leading causes of preventable death, killing nearly 6 million people worldwide each year, the researchers recommended that the FDA and European Medicines Agency re-examine whether their warnings about the drug are necessary.

“To not prescribe the most effective smoking cessation drug on any given occasion is likely to lead to substantial loss of life expectancy even if the patient stops later in life, because patients lose, on average, 3 months of life expectancy for each year of continued smoking.”


  1. Kotz D, Viechtbauer W, Simpson C, et al. Cardiovascular and neuropsychiatric risks of varenicline: a retrospective cohort study. Lancet Respir Med. 2015:doi:http://dx.doi.org/10.1016/S2213-2600(15)00320-3.