BACKGROUND: Stopping smoking is associated with many important improvements in 
health and quality of life. The use of cessation medications is recommended to 
increase the likelihood of quitting. However, there is historical and renewed 
concern that smoking cessation therapies may increase the risk of cardiovascular 
disease events associated within the quitting period. We aimed to examine 
whether the 3 licensed smoking cessation therapies-nicotine replacement therapy, 
bupropion, and varenicline-were associated with an increased risk of 
cardiovascular disease events using a network meta-analysis.
METHODS AND RESULTS: We searched 10 electronic databases, were in communication 
with authors of published randomized, clinical trials (RCTs), and accessed 
internal US Food and Drug Administration reports. We included any RCT of the 3 
treatments that reported cardiovascular disease outcomes. Among 63 eligible RCTs 
involving 21 nicotine replacement therapy RCTs, 28 bupropion RCTs, and 18 
varenicline RCTs, we found no increase in the risk of all cardiovascular disease 
events with bupropion (relative risk [RR], 0.98; 95% confidence interval [CI], 
0.54-1.73) or varenicline (RR, 1.30; 95% CI, 0.79-2.23). There was an elevated 
risk associated with nicotine replacement therapy that was driven predominantly 
by less serious events (RR, 2.29; 95% CI, 1.39-3.82). When we examined major 
adverse cardiovascular events, we found a protective effect with bupropion (RR, 
0.45; 95% CI, 0.21-0.85) and no clear evidence of harm with varenicline (RR, 
1.34; 95% CI, 0.66-2.66) or nicotine replacement therapy (RR, 1.95; 95% CI, 
0.26-4.30).
CONCLUSION: Smoking cessation therapies do not appear to raise the risk of 
serious cardiovascular disease events.