Cardiovascular Events Associated With Smoking Cessation Pharmacotherapies: A Network Meta-Analysis

Study Questions:

Do smoking cessation therapies including nicotine replacement therapy, bupropion, and varenicline increase the risk for cardiovascular disease (CVD) events?


Randomized clinical trials and US Food and Drug (FDA) reports were identified for inclusion in this meta-analysis. Literature searches were performed in 10 electronic databases. Any randomized clinical trials of the three treatments (nicotine replacement therapy, bupropion, and varenicline) that reported on CVD outcomes were included.


Among 63 eligible randomized clinical trials, 21 examined nicotine replacement therapy, 28 examined bupropion, and 18 examined varenicline therapy. No increase in the risk of CVD events was observed for bupropion trials (relative risk [RR], 0.98; 95% confidence interval [CI], 0.54-1.73) or varenicline trials (RR, 1.30; 95% CI, 0.79-2.23). However, there was an elevated risk associated with nicotine replacement therapy that was predominantly driven by less serious events (RR, 2.29; 95% CI, 1.39-3.82). When major adverse cardiac events (MACE) were examined, a protective effect was observed for bupropion (RR, 0.45; 95% CI, 0.21-0.85). No clear evidence of harm was observed for varenicline (RR, 1.34; 95% CI, 0.66-2.66) or for nicotine replacement therapy (RR, 1.95; 95% CI, 0.26-4.30).


The investigators concluded that smoking cessation therapies do not appear to raise the risk of serious CVD events.


This meta-analysis supports the use of nicotine replacement therapy, bupropion, or varenicline for use in smoking cessation among patients at risk for CVD. However, as the authors suggest, evidence regarding electronic cigarettes is limited at this time.

Keywords: Risk, Nicotine, Cardiovascular Diseases, Confidence Intervals, Quinoxalines, Smoking Cessation, Benzazepines, United States, Bupropion

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