A Comparative Effectiveness & Long-term Health Study in Wisconsin Smokers

描述（由申请人提供）：虽然吸烟的健康风险是众所周知的，但重要的问题仍然是关于烟草使用、戒烟以及戒烟对当今吸烟者的健康益处。拟议的研究通过三个主要的具体目标来解决这些问题：1)通过进行比较有效性试验，首次直接将两种戒烟药物疗法与现有最有力的疗效证据（NRT和伐尼克兰联合）进行对比，产生关于如何最佳治疗吸烟的新数据；2)确定当今吸烟者戒烟对生物标志物和健康危险因素的影响，特别是对心血管疾病（CVD）的影响，这将阐明戒烟对健康有益的机制；3)确定因持续吸烟而使生物标志物或危险因素状态恶化的风险最大的个体，以及从戒烟中获益最多的个体。拟议的研究将解决两个次要目标：1)为当今吸烟者的最佳治疗开发一种治疗分配算法；2)确定健康生物标志物与疾病结局（如心血管疾病事件）的关系。这些目标必须在当代吸烟者人群中得到解决，因为今天的吸烟者在体重、性别分布、饮食、社会经济地位和其他可能影响戒烟风险和健康影响的因素的基础上与早期研究中的吸烟者不同。我们将从一项正在进行的吸烟与健康纵向研究中招募900人（“持续参与者”，包括吸烟者和成功戒烟者），以及600名新吸烟者（“新招募参与者”），为这项新研究提供1500名参与者。所有新招募的参与者和一些继续参与的参与者（总N=1150）将参加一项比较有效性的试验，该试验直接比较两种最有效的戒烟疗法（伐尼克兰与联合尼古丁替代疗法：每种治疗N=475），以及一种积极的比较治疗（尼古丁贴片，N=200）。所有参与者（N=1500）将被评估至少3年。评估生物标志物和健康结果的总时间对于新招募的参与者为3-4年，对于持续参与者为8-9年。疾病风险的生物标志物将侧重于心血管疾病标志物（例如，颈动脉厚度、动脉硬度、压力测试、炎症），包括心血管疾病所有主要危险因素的测量。我们将使用这些和其他措施来确定最有可能从戒烟中受益的吸烟者，并确定不良吸烟相关健康事件的病因（即动脉粥样硬化进展、动脉硬化和氧化应激）。总之，这项研究将在吸烟的治疗、吸烟相关疾病的机制、戒烟的好处以及识别最容易发生不良心血管疾病或其他健康事件的吸烟者方面产生重要的新数据。虽然所有吸烟者都应该戒烟，但我们的研究结果最终可能有助于集中治疗，并激励吸烟者和临床医生对风险最大的患者进行更深入的干预。

DESCRIPTION (provided by applicant): While the health risks of smoking are well known, vital questions remain about tobacco use, smoking cessation, and the health benefits of cessation in today's smokers. The proposed research addresses these questions via three primary specific aims: 1) Produce new data on how to treat smoking optimally by conducting a comparative effectiveness trial that for the first time directly contrasts the two smoking cessation pharmacotherapies with the strongest extant evidence of efficacy (combination NRT and varenicline); 2) Determine the impact of smoking cessation in today's smokers on biomarkers and health risk factors, especially for cardiovascular disease (CVD), which will elucidate the mechanisms by which cessation benefits health; and, 3) Identify individuals who are at greatest risk for exacerbation of biomarkers or risk factor status due to continued smoking, and who benefit most from cessation. The proposed research will address two secondary aims: 1) to develop a treatment assignment algorithm for the optimal treatment of today's smokers; and, 2) to determine the relation of health biomarkers to disease outcomes such as CVD events. These aims must be addressed in a contemporary population of smokers because today's smokers differ from smokers in earlier studies on the basis of weight, sex distribution, diet, socioeconomic status, and other factors that might affect the risks and the health effects of cessation. We will recruit 900 persons from an ongoing longitudinal study of smoking and health ("continuing participants," including both smokers and successful quitters), and 600 new, current smokers for this trial ("newly recruited participants"), providing 1500 total participants for this new study. All of the newly recruited and some of the continuing participants (total N=1150), will enroll in a comparative effectiveness trial that directly compares the two most effective smoking cessation therapies (varenicline vs. combination nicotine replacement therapy: N=475 for each treatment) with one another, and with an active comparator treatment (the nicotine patch; N=200). All participants (N=1500) will be evaluated for a minimum of 3 years. The total time for assessing biomarkers and health outcomes will 3-4 years for newly recruited participants and 8-9 years for the continuing participants. Biomarkers of disease risk will focus on CVD markers (e.g., carotid thickness, arterial stiffness, stress testing, inflammation) including measures for all major risk factors for CVD. We will use these and other measures to identify smokers who are most likely to benefit from cessation, and to identify etiologies (i.e., atherosclerosis progression, arterial stiffening, and oxidant stress) for adverse, smoking-related health events. In sum, this research will produce important new data on the treatment of smoking, the mechanisms of smoking-related disease, the benefits of cessation, and identification of smokers who are at greatest risk for an adverse CVD or other health events. While all smokers should quit, our findings could ultimately help focus treatment and motivate smokers and clinicians to intervene more intensively with patients at greatest risk.