title: Varenicline and Adverse Cardiovascular Events: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.
abstract: 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.
  
  
  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.
authors.affiliation: Division of Clinical Epidemiology, Lady Davis Institute, Jewish General Hospital/McGill University, Montreal, Quebec, Canada Faculty of Medicine, McGill University, Montreal, Quebec, Canada.
authors.forename: Lee H
authors.initials: LH
authors.lastname: Sterling
authors.affiliation: Division of Clinical Epidemiology, Lady Davis Institute, Jewish General Hospital/McGill University, Montreal, Quebec, Canada.
authors.forename: Sarah B
authors.initials: SB
authors.lastname: Windle
authors.affiliation: Division of Clinical Epidemiology, Lady Davis Institute, Jewish General Hospital/McGill University, Montreal, Quebec, Canada Faculty of Medicine, McGill University, Montreal, Quebec, Canada Department of Epidemiology, Biostatistics and Occupational Health, McGill University, Montreal, Quebec, Canada.
authors.forename: Kristian B
authors.initials: KB
authors.lastname: Filion
authors.affiliation: Division of Clinical Epidemiology, Lady Davis Institute, Jewish General Hospital/McGill University, Montreal, Quebec, Canada Faculty of Medicine, McGill University, Montreal, Quebec, Canada.
authors.forename: Lahoud
authors.initials: L
authors.lastname: Touma
authors.affiliation: Division of Clinical Epidemiology, Lady Davis Institute, Jewish General Hospital/McGill University, Montreal, Quebec, Canada Division of Cardiology, Jewish General Hospital/McGill University, Montreal, Quebec, Canada Faculty of Medicine, McGill University, Montreal, Quebec, Canada Department of Epidemiology, Biostatistics and Occupational Health, McGill University, Montreal, Quebec, Canada mark.eisenberg@mcgill.ca.
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Eisenberg
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002318:Cardiovascular Diseases / Q000139:chemically induced* / Q000175:diagnosis / Q000401:mortality; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D018722:Nicotinic Agonists / Q000009:adverse effects*; D016017:Odds Ratio; D016032:Randomized Controlled Trials as Topic; D018570:Risk Assessment; D012307:Risk Factors; D000074606:Smoking Prevention; D061485:Tobacco Use Cessation Devices / Q000009:adverse effects*; D014029:Tobacco Use Disorder / Q000188:drug therapy*; D000068580:Varenicline / Q000009:adverse effects*; D055815:Young Adult
chemical_list: D018722:Nicotinic Agonists; D000068580:Varenicline
keywords: cardiovascular disease; meta‐analysis; smoking cessation; systematic review; varenicline