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NRT was associated with an increase in cardiovascular events, but not major cardiovascular events, when compared to placebo in a network meta-analysis that included individuals both with and without heart disease.(129) A study that specifically focused on outpatient smokers with CVD found no significant increase in cardiovascular events (death, myocardial infarction, cardiac arrest, or hospital admission for worsening angina, arrhythmia, or heart failure) among smokers receiving nicotine patch versus placebo.(130) Varenicline is a partial nicotinic receptor agonist that more than doubles smoking abstinence rates compared to placebo (RR 2.24, 95% CI 2.062.43).(131) The EAGLES trial, which randomized more than 8000 smokers in 16 countries to varenicline, bupropion, nicotine patch, or placebo in a 1:1:1:1 ratio, found a significantly higher 6-month abstinence rate for the varenicline group compared to all other groups.(132) In a randomized trial of smokers with stable CVD, treatment with varenicline increased the odds of continuous abstinence at 1 year over placebo (OR 3.14, 95% 1.945.11).(133) A randomized trial of smokers with acute coronary syndrome found a higher rate of continuous abstinence at 24 weeks and a higher point- prevalence abstinence rate at 52 weeks in those taking varenicline vs

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