E vidence-based pharmacotherapy for

E vidence-based pharmacotherapy for smoking cessation has been shown to be effective in diverse populations of thosewho smoke,1and different strategies to enhance the effectiveness of such therapies have been explored.2Research has supported the effectiveness of combinationtherapy with varenicline and nicotine replacement therapy(NRT) vs varenicline alone. One large study3 reported significant benefit of combination therapy with varenicline and NRTvs varenicline alone. Two smaller studies4,5did not show a statistically significant benefit with this treatment, but a metaanalysis of the 3 studies showed a statistically significant association with benefit.6 Such evidence led the American ThoracicSociety to conditionally recommend varenicline plus nicotinepatch combination therapy over varenicline monotherapy forsmoking cessation.7 However, most guidelines recommendmonotherapy with varenicline, NRT, or bupropion or recommend combination therapy with different types of NRT.8,9There is also evidence that extending the duration of pharmacotherapy can enhance its effectiveness.10-12However, littleresearch has been done on extended varenicline treatment. Tworelapse prevention studies13,14 and a Cochrane meta-analysis15found that extended treatment with varenicline can increaselong-term abstinence rates among individuals who already attained abstinence after prior treatment.Because it remains uncertain whether combining varenicline with NRT or extending varenicline treatment duration increases smoking cessation rates, this randomized clinical trialwas conducted to examine both treatment strategies amongindividuals expressing an interest in quitting smoking.