Varenicline and Adverse Cardiovascular Events: A Systematic Review and Meta‐Analysis of Randomized Controlled Trials

Abstract

BackgroundVarenicline 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.Methods and ResultsWe 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.ConclusionsWe 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.

Tackling smoking cessation systematically among inpatients with heart disease

“…The largest meta-analysis of the cardiovascular safety of varenicline to date, which was published recently, included data from 38 studies and 12 706 smokers, including those with and without pre-existing cardiovascular disease. 11 The occurrence of the combination of cardiovascular serious adverse events and mortality was 0.79% in the varenicline group versus 0.78% in the placebo group. Results were similar between those with and without pre-existing cardiovascular disease.…”

Varenicline: mode of action, efficacy, safety and accumulated experience salient for clinical populations

“…Some meta-analyses concerning the CV safety of varenicline have suggested CV risk to marginally increase in smokers who receive varenicline versus placebo 81,82 while others have reported no differences 83,84 , even when focusing on smokers with previous CVD or predisposing conditions (Supplementary Table 2). This disparity has been attributed to the limited size and duration of varenicline RCTs and to a low incidence of CV events within such trials 85 , as well as differences in methodology among the analyses. A recent, large meta-analysis that included 38 RCTs (N ¼ 12,706) of smokers found that CV events were rare overall and there were no differences in serious CV AEs between varenicline-and placebo-treated smokers (RR, 1.03; 95% CI: 0.72, 1.49) 85 .…”

“…This disparity has been attributed to the limited size and duration of varenicline RCTs and to a low incidence of CV events within such trials 85 , as well as differences in methodology among the analyses. A recent, large meta-analysis that included 38 RCTs (N ¼ 12,706) of smokers found that CV events were rare overall and there were no differences in serious CV AEs between varenicline-and placebo-treated smokers (RR, 1.03; 95% CI: 0.72, 1.49) 85 . Furthermore, similar findings were observed when the analysis was stratified by smokers with and without CVD (RR, 1.04; 95% CI: 0.57, 1.89; RR, 1.03; 95% CI: 0.64, 1.64, respectively).…”

Modern pharmaceutical methods of treatment of tobacco smoking

“…Относительный риск нежелательных сердечно-сосудистых событий достоверно не различался у пациентов, получавших терапию варениклином или плацебо (относительный риск (ОР) 1,03; 95% ДИ 0,72-1,49). При этом ОР нежелательных сердечно-сосудистых событий достоверно не различался у пациентов с хроническими заболеваниями сердечно-сосудистой системы и без хронических заболеваний, получавших терапию варениклином или плацебо: у пациентов с сердечно-сосудистой патологией -ОР 1,04; 95% ДИ 0,57-1,89; у пациентов без сердечно-сосудистой патологии -ОР 1,03; 95% ДИ 0,64-1,64 [14].…”