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Review
. 2012 May 4:344:e2856.
doi: 10.1136/bmj.e2856.

Risk of cardiovascular serious adverse events associated with varenicline use for tobacco cessation: systematic review and meta-analysis

Judith J Prochaska  1 , Joan F Hilton
Affiliations
Review

Risk of cardiovascular serious adverse events associated with varenicline use for tobacco cessation: systematic review and meta-analysis

Judith J Prochaska et al. BMJ. .

Abstract

Objective: To examine the risk of treatment emergent, cardiovascular serious adverse events associated with varenicline use for tobacco cessation.

Design: Meta-analysis comparing study effects using four summary estimates.

Data sources: Medline, Cochrane Library, online clinical trials registries, and reference lists of identified articles.

Review methods: We included randomised controlled trials of current tobacco users of adult age comparing use of varenicline with an inactive control and reporting adverse events. We defined treatment emergent, cardiovascular serious adverse events as occurring during drug treatment or within 30 days of discontinuation, and included any ischaemic or arrhythmic adverse cardiovascular event (myocardial infarction, unstable angina, coronary revascularisation, coronary artery disease, arrhythmias, transient ischaemic attacks, stroke, sudden death or cardiovascular related death, or congestive heart failure).

Results: We identified 22 trials; all were double blinded and placebo controlled; two included participants with active cardiovascular disease and 11 enrolled participants with a history of cardiovascular disease. Rates of treatment emergent, cardiovascular serious adverse events were 0.63% (34/5431) in the varenicline groups and 0.47% (18/3801) in the placebo groups. The summary estimate for the risk difference, 0.27% (95% confidence interval -0.10 to 0.63; P = 0.15), based on all 22 trials, was neither clinically nor statistically significant. For comparison, the relative risk (1.40, 0.82 to 2.39; P = 0.22), Mantel-Haenszel odds ratio (1.41, 0.82 to 2.42; P = 0.22), and Peto odds ratio (1.58, 0.90 to 2.76; P = 0.11), all based on 14 trials with at least one event, also indicated a non-significant difference between varenicline and placebo groups.

Conclusions: This meta--analysis--which included all trials published to date, focused on events occurring during drug exposure, and analysed findings using four summary estimates-found no significant increase in cardiovascular serious adverse events associated with varenicline use. For rare outcomes, summary estimates based on absolute effects are recommended and estimates based on the Peto odds ratio should be avoided.

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Conflict of interest statement

Competing interests: All authors have completed the Unified Competing Interest form at www.icmje.org/coi_disclosure.pdf (available on request from the corresponding author) and declare: this study received support from the National Institute on Drug Abuse and the State of California Tobacco-Related Disease Research Program; JJP is principal investigator on R01 MH083684 from the National Institute of Mental Health and an Investigator Initiated Research award from Pfizer (WS981308), and is a collaborator on R34 DA030538 from the National Institute on Drug Abuse and a Cahan Award from the Flight Attendant Medical Research Institute, all of which are tobacco control trials; JFH is coinvestigator on five randomised controlled trials funded by the National Institutes of Health and the Agency for Healthcare Research and Quality, none of which are relevant to the submitted work; JFH has had no relationship with any company that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted work.

Figures

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Fig 1 Literature search results and study selection
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Fig 2 Difference in risk of treatment emergent, cardiovascular serious adverse events associated with varenicline use in 22 double blinded, placebo controlled, randomised trials. Studies grouped by presence (v absence) of events and equal (v unequal) numbers of events with groups ordered by increasing evidence of a varenicline effect
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Fig 3 Cumulative estimated difference in risk of cardiovascular serious adverse events attributable to varenicline use. Studies ordered by publication year
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