PT  - JOURNAL ARTICLE
AU  - Sonal Singh
AU  - Yoon K. Loke
AU  - John G. Spangler
AU  - Curt D. Furberg
TI  - Risk of serious adverse cardiovascular events associated with varenicline: a systematic review and meta-analysis
AID  - 10.1503/cmaj.110218
DP  - 2011 Sep 06
TA  - Canadian Medical Association Journal
PG  - 1359--1366
VI  - 183
IP  - 12
4099  - http://www.cmaj.ca/content/183/12/1359.short
4100  - http://www.cmaj.ca/content/183/12/1359.full
SO  - CMAJ2011 Sep 06; 183
AB  - Background: There have been postmarketing reports of adverse cardiovascular events associated with the use of varenicline, a widely used smoking cessation drug. We conducted a systematic review and meta-analysis of randomized controlled trials to ascertain the serious adverse cardiovascular effects of varenicline compared with placebo among tobacco users. Methods: We searched MEDLINE, EMBASE, the Cochrane Database of Systematic Reviews, websites of regulatory authorities and registries of clinical trials, with no date or language restrictions, through September 2010 (updated March 2011) for published and unpublished studies. We selected double-blind randomized controlled trials of at least one week’s duration involving smokers or people who used smokeless tobacco that reported on cardiovascular events (ischemia, arrhythmia, congestive heart failure, sudden death or cardiovascular-related death) as serious adverse events asociated with the use of varenicline. Results: We analyzed data from 14 double-blind randomized controlled trials involving 8216 participants. The trials ranged in duration from 7 to 52 weeks. Varenicline was associated with a significantly increased risk of serious adverse cardiovascular events compared with placebo (1.06% [52/4908] in varenicline group v. 0.82% [27/3308] in placebo group; Peto odds ratio [OR] 1.72, 95% confidence interval [CI] 1.09–2.71; I2 = 0%). The results of various sensitivity analyses were consistent with those of the main analysis, and a funnel plot showed no publication bias. There were too few deaths to allow meaningful comparisons of mortality. Interpretation: Our meta-analysis raises safety concerns about the potential for an increased risk of serious adverse cardiovascular events associated with the use of varenicline among tobacco users.See related commentary by Hays on page 1346 and at www.cmaj.ca/lookup/doi/10.1503/cmaj.110804 and related letters on page 1404.