Cytisine increases the chances of quitting, although absolute quit rates were modest in two recent trials. Varenicline at standard dose increased the chances of successful long-term smoking cessation between two- and threefold compared with pharmacologically unassisted quit attempts. Lower dose regimens also conferred benefits for cessation, while reducing the incidence of adverse events. More participants quit successfully with varenicline than with bupropion. Two open-label trials of varenicline versus NRT suggested a modest benefit of varenicline but confidence intervals did not rule out equivalence. Limited evidence suggests that varenicline may have a role to play in relapse prevention. The main adverse effect of varenicline is nausea, but mostly at mild to moderate levels and tending to subside over time. Possible links with serious adverse events, including serious psychiatric or cardiovascular events, cannot be ruled out.

Future trials of cytisine may test extended regimens and more intensive behavioural support. There is a need for further trials of the efficacy of varenicline treatment extended beyond 12 weeks.
Efficacy and safety of varenicline for smoking cessation in patients with cardiovascular disease: a randomized trial.
Smoking cessation is a key component of secondary cardiovascular disease prevention. Varenicline, a partial alpha4beta2 nicotinic acetylcholine receptor agonist, is effective for smoking cessation in healthy smokers, but its efficacy and safety in smokers with cardiovascular disease are unknown.
                A multicenter, randomized, double-blind, placebo-controlled trial compared the efficacy and safety of varenicline with placebo for smoking cessation in 714 smokers with stable cardiovascular disease. Participants received varenicline (1 mg twice daily) or placebo, along with smoking-cessation counseling, for 12 weeks. Follow-up lasted 52 weeks. The primary end point was carbon monoxide-confirmed continuous abstinence rate for weeks 9 through 12 (last 4 weeks of treatment). The continuous abstinence rate was higher for varenicline than placebo during weeks 9 through 12 (47.0% versus 13.9%; odds ratio, 6.11; 95% confidence interval [CI], 4.18 to 8.93) and weeks 9 through 52 (19.2% versus 7.2%; odds ratio, 3.14; 95% CI, 1.93 to 5.11). The varenicline and placebo groups did not differ significantly in cardiovascular mortality (0.3% versus 0.6%; difference, -0.3%; 95% CI, -1.3 to 0.7), all-cause mortality (0.6% versus 1.4%; difference, -0.8%; 95% CI, -2.3 to 0.6), cardiovascular events (7.1% versus 5.7%; difference, 1.4%; 95% CI, -2.3 to 5.0), or serious adverse events (6.5% and 6.0%; difference, 0.5%; 95% CI, -3.1 to 4.1). As a result of adverse events, 9.6% of varenicline and 4.3% of placebo participants discontinued study drug.
                Varenicline is effective for smoking cessation in smokers with cardiovascular disease. It was well tolerated and did not increase cardiovascular events or mortality; however, trial size and duration limit definitive conclusions about safety. Clinical Trial Registration Information- URL: http://www.clinicaltrials.gov/ct2/show/NCT00282984. Unique identifier: NCT00282984.