Background
Smoking is a leading preventable cause of morbidity and premature death worldwide. It has been well established that smoking increases risk of respiratory disease, cardiovascular disease, diabetes mellitus, autoimmune disorders, reproductive system disorders, and many kinds of cancers. Varenicline not only acts as a partial agonist to attenuate withdrawal symptoms during smoking cessation, but also as an agent to block nicotine binding. In a guideline proposed to treat tobacco use and dependence in 2008, seven first-line medications were recommended (nicotine in the forms of gum, inhaler, lozenge, nasal spray and patch, sustained release bupropion hydrochloride, and varenicline). Among them, varenicline had the highest abstinence rate. A meta-analysis revealed that varenicline was more effective than standard-dose nicotine replacement therapy (NRT) (relative risk = 1.38, 95 % CI 1.15 to 1.64 at 6 months), but was similar to high-dose NRT (relative risk = 1.05, 95 % CI 0.80 to 1.36 at 6 months). In another meta-analysis, although varenicline was still regarded as the most effective mono-therapy, it was not superior to combination therapy of two different types of NRT [odds ratio (OR) = 1.06, 95 % CI 0.75 to 1.48].
Combination therapy of varenicline with other medications was not recommended in the guideline proposed by the National Institute for Health and Care Excellence (NICE). Combination therapy of varenicline with NRT is not recommended either by the US Public Health Clinical Practice Guideline for Treating Tobacco Use and Dependence. The efficacy of combination therapy was inconsistent. A retrospective study revealed that the combination therapy of varenicline and NRT was tolerable, but was not superior to mono-therapy. One randomized controlled trial (RCT) showed that varenicline combined with nicotine patch was more effective than varenicline alone to achieve continuous abstinence rate at 12 and 24 weeks. However, another two RCTs showed no superior effects. This research aimed to evaluate the efficacy and safety of varenicline combined with NRT through a systematic review and meta-analysis of RCTs.