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Meta-Analysis
. 2011 Sep 6;183(12):1359-66.
doi: 10.1503/cmaj.110218. Epub 2011 Jul 4.

Risk of serious adverse cardiovascular events associated with varenicline: a systematic review and meta-analysis

Sonal Singh  1 , Yoon K Loke, John G Spangler, Curt D Furberg
Affiliations
Meta-Analysis

Risk of serious adverse cardiovascular events associated with varenicline: a systematic review and meta-analysis

Sonal Singh et al. CMAJ. .

Abstract

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clinical trials, with no date or language restrictions, through September 2010 (updated March 2011) for published and unpublished studies.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; I(2) = 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.

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Figures

Figure 1:
Figure 1:
Selection of double-blind placebo-controlled randomized controlled trials (RCTs) for inclusion in the systematic review and meta-analysis of the risk of serious adverse cardiovascular events associated with varenicline use. *An additional open-label trial of varenicline versus nicotine replacement therapy was included in the sensitivity analysis.
Figure 2:
Figure 2:
Meta-analysis of double-blind placebo-controlled randomized trials of the risk of serious adverse cardiovascular events associated with the use of varenicline. An odds ratio (OR) greater than 1.0 indicates an increased risk of a serious adverse cardiovascular event. CI = confidence interval.
See this image and copyright information in PMC

Comment in

References

    1. Cahill K, Stead LF, Lancaster T. Nicotine receptor partial agonists for smoking cessation. Cochrane Database Syst Rev 2011;(2): CD006103. - PubMed
    1. Mihalak KB, Carroll FI, Luetje CW. Varenicline is a partial agonist at alpha 4 beta 2 and a full agonist at alpha 7 neuronal nico tinic receptors. Mol Pharmacol 2006;70:801–5 - PubMed
    1. Wang J, Wang X, Irnaten M, et al. Endogenous acetylcholine and nicotine activation enhances GABAergic and glycinergic inputs to cardiac vagal neurons. J Neurophysiol 2003;89:2473–81 - PubMed
    1. Lindenblatt N, Platz U, Hameister J, et al. Distinct effects of acute and chronic nicotine application on microvascular thrombus formation and endothelial function in male and female mice. Langenbecks Arch Surg 2007;392:285–95 - PubMed
    1. Josefberg H. Approval package for: application number NDA 21–928 [clinical safety review: varenicline tartrate]. Rockville (MD): US Food and Drug Administration, Center for Drug Evaluation and Research; 2006. p. 277, 402 Available: www.accessdata.fda.gov/drugsatfda_docs/nda/2006/021928_s000_Chantix_MedR... (accessed 2011 Apr. 14).

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