INTRODUCTION: Smoking is a major avoidable cause of ill-health and @entity204 . Treatments that help @entity1 successfully quit smoking have an important effect on health and life expectancy. @entity4006 is a medication that can help smokers successfully quit smoking. However, there are concerns that it may cause adverse effects, such as increase in the occurrence of @entity308 , self-harm and suicide and @entity65 . In this study we aim to examine the effects of @entity4006 versus other smoking cessation pharmacotherapies on smoking cessation, health service use, all-cause and cause-specific mortality and physical and mental health conditions. METHODS: In this project we will investigate the effects of @entity4006 compared to @entity1239 replacement therapies on: (1) long-term smoking cessation and whether these effects differ by area level deprivation; and (2) the following clinically-important outcomes: rate of general practice and hospital attendance; all-cause mortality and @entity204 due to @entity17220 and @entity65 ; and a primary care diagnosis of @entity1576 , @entity583 or @entity308 and @entity148 . The study is based on a cohort of @entity1 prescribed these smoking cessation medications from the Clinical Practice Research Datalink (CPRD). We will use three methods to overcome confounding: multivariable adjusted Cox regression, propensity score matched Cox regression, and instrumental variable regression. The total expected sample size for analysis will be at least 180   000. Follow-up will end with the earliest of either an 'event' or censoring due to the end of registration or @entity204 . ETHICS AND DISSEMINATION: Ethics approval was not required for this study. This project has been approved by the CPRD's Independent Scientific Advisory Committee (ISAC). We will disseminate our findings via publications in international peer-reviewed journals and presentations at international conferences.

What are the effects of XXXX compared with @entity1239 replacement therapy on long-term smoking cessation and clinically important outcomes? Protocol for a prospective cohort study.

@entity1 :: ('9606', 'Species') :: ['patients'] @entity308 :: ('MESH:D003866', 'Disease') :: ['depression'] @entity4006 :: ('MESH:C500838', 'Chemical') :: ['varenicline', 'Varenicline'] @entity1239 :: ('MESH:D009538', 'Chemical') :: ['nicotine'] @entity17220 :: ('MESH:D015619', 'Disease') :: ['diseases of the respiratory system'] @entity148 :: ('MESH:D001008', 'Disease') :: ['anxiety'] @entity1576 :: ('MESH:D012131', 'Disease') :: ['respiratory illness'] @entity583 :: ('MESH:D009203', 'Disease') :: ['myocardial infarction'] @entity204 :: ('MESH:D003643', 'Disease') :: ['death', 'premature death'] @entity65 :: ('MESH:D002318', 'Disease') :: ['cardiovascular disease']
@entity4006 :: (MESH:C500838,Chemical) :: ['varenicline']
