Cardiovascular and Neuropsychiatric Events after Varenicline Use for Smoking Cessation

Am J Respir Crit Care Med. 2018 Apr 1;197(7):913-922. doi: 10.1164/rccm.201706-1204OC.


Rationale: Varenicline aids in smoking cessation but has also been associated with serious adverse events.

Objectives: The aim of this study was to determine the risks of cardiovascular and neuropsychiatric events after varenicline receipt in a real-world setting.

Methods: A population-based, self-controlled risk interval study using linked universal health administrative data from the diverse, multicultural population of Ontario, Canada, was conducted. In two separate analyses, new varenicline users between September 1, 2011 and February 15, 2014 were observed from 1 year before to 1 year after varenicline receipt. The relative incidences of cardiovascular and neuropsychiatric hospitalizations and emergency department visits in the 12 weeks after varenicline receipt (the risk interval) compared with the remaining observation period (the control interval) were estimated in two separate fixed-effect conditional Poisson regressions. Sensitivity analyses tested the robustness of the results.

Measurements and main results: Among 56,851 new users of varenicline, 6,317 cardiovascular and 10,041 neuropsychiatric hospitalizations and emergency department visits occurred from 1 year before to 1 year after receipt. The incidence of cardiovascular events was 34% higher in the risk compared with the control interval (relative incidence, 1.34; 95% confidence interval, 1.25-1.44). Findings were consistent in sensitivity analyses, most notably in those without any history of previous cardiovascular disease. The relative incidence of neuropsychiatric events was marginally significant in the primary (relative incidence, 1.06; 95% confidence interval, 1.00-1.13) but not all sensitivity analyses.

Conclusions: Varenicline appears to be associated with an increased risk of cardiovascular but not neuropsychiatric events.

Keywords: drug safety; smoking cessation; varenicline.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Cardiovascular Diseases / chemically induced*
  • Emergency Service, Hospital / statistics & numerical data
  • Female
  • Hospitalization / statistics & numerical data
  • Humans
  • Male
  • Mental Disorders / chemically induced*
  • Middle Aged
  • Nicotinic Agonists / adverse effects*
  • Ontario
  • Smoking Cessation / methods*
  • Varenicline / adverse effects*


  • Nicotinic Agonists
  • Varenicline