Combination Therapy of Varenicline With Nicotine Replacement Therapy Is Better Than Varenicline Alone

A Systematic Review and Meta-analysis of Randomized Controlled Trials

Ping-Hsun Chang; Chien-Hsieh Chiang; Wei-Che Ho; Pei-Zu Wu; Jaw-Shiun Tsai; Fei-Ran Guo


BMC Public Health. 2015;15(689) 

In This Article


Smoking is a leading preventable cause of morbidity and premature death worldwide.[1] 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.[2] Varenicline not only acts as a partial agonist to attenuate withdrawal symptoms during smoking cessation, but also as an agent to block nicotine binding.[3] 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).[4] 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).[5] 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].[6]

Combination therapy of varenicline with other medications was not recommended in the guideline proposed by the National Institute for Health and Care Excellence (NICE).[7] Combination therapy of varenicline with NRT is not recommended either by the US Public Health Clinical Practice Guideline for Treating Tobacco Use and Dependence.[4] 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.[8] 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.[9] However, another two RCTs showed no superior effects.[10,11] This research aimed to evaluate the efficacy and safety of varenicline combined with NRT through a systematic review and meta-analysis of RCTs.