Varenicline and Adverse Cardiovascular Events: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

J Am Heart Assoc. 2016 Feb 22;5(2):e002849. doi: 10.1161/JAHA.115.002849.


Background: Varenicline is an efficacious smoking-cessation drug. However, previous meta-analyses provide conflicting results regarding its cardiovascular safety. The publication of several new randomized controlled trials (RCTs) provides an opportunity to reassess this potential adverse drug reaction.

Methods and results: We searched MEDLINE, EMBASE, and the Cochrane Library for RCTs that compare varenicline with placebo for smoking cessation. RCTs reporting cardiovascular serious adverse events and/or all-cause mortality during the treatment period or within 30 days of treatment discontinuation were eligible for inclusion. Relative risks (RRs) with 95% CIs were generated by using DerSimonian-Laird random-effects models. Thirty-eight RCTs met our inclusion criteria (N=12 706). Events were rare in both varenicline (57/7213) and placebo (43/5493) arms. No difference was observed for cardiovascular serious adverse events when comparing varenicline with placebo (RR 1.03, 95% CI 0.72-1.49). Similar findings were obtained when examining cardiovascular (RR 1.04, 95% CI 0.57-1.89) and noncardiovascular patients (RR 1.03, 95% CI 0.64-1.64). Deaths were rare in both varenicline (11/7213) and placebo (9/5493) arms. Although 95% CIs were wide, pooling of all-cause mortality found no difference between groups (RR 0.88, 95% CI 0.50-1.52), including when stratified by participants with (RR 1.24, 95% CI 0.40-3.83) and without (RR 0.77, 95% CI 0.40-1.48) cardiovascular disease.

Conclusions: We found no evidence that varenicline increases the rate of cardiovascular serious adverse events. Results were similar among those with and without cardiovascular disease. Given varenicline's efficacy as a smoking cessation drug and the long-term cardiovascular benefits of cessation, it should continue to be prescribed for smoking cessation.

Keywords: cardiovascular disease; meta‐analysis; smoking cessation; systematic review; varenicline.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't
  • Review
  • Systematic Review

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Cardiovascular Diseases / chemically induced*
  • Cardiovascular Diseases / diagnosis
  • Cardiovascular Diseases / mortality
  • Female
  • Humans
  • Male
  • Middle Aged
  • Nicotinic Agonists / adverse effects*
  • Odds Ratio
  • Randomized Controlled Trials as Topic
  • Risk Assessment
  • Risk Factors
  • Smoking Prevention*
  • Tobacco Use Cessation Devices / adverse effects*
  • Tobacco Use Disorder / drug therapy*
  • Varenicline / adverse effects*
  • Young Adult


  • Nicotinic Agonists
  • Varenicline