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，但关于烟草使用，戒烟以及戒烟对当今吸烟者的健康益处的重要问题仍然存在。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，首次直接对比两种戒烟药物疗法的最佳疗效，产生关于如何最佳治疗吸烟的新数据。（NRT和伐尼克兰组合）; 2）确定当今吸烟者戒烟对生物标志物和健康风险因素的影响，特别是对心血管疾病（CVD）的影响，这将阐明戒烟有益于健康的机制;以及3）识别由于持续吸烟而处于生物标志物或风险因素状态恶化的最大风险中的个体，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）开发一种治疗分配算法，用于当今吸烟者的最佳治疗; 2）确定健康生物标志物与疾病结局（如CVD事件）的关系。这些目标必须在当代吸烟人群中得到解决，因为今天的吸烟者与早期研究中的吸烟者在体重，性别分布，饮食，社会经济地位以及可能影响戒烟风险和健康影响的其他因素方面有所不同。我们将从一项正在进行的吸烟与健康纵向研究中招募900名受试者（"持续参与者"，包括吸烟者和成功戒烟者），并招募600名新的当前吸烟者参加本试验（"新招募的参与者"），总共为这项新研究提供1500名参与者。所有新招募的受试者和一些继续参与的受试者（总N = 1150）将入组一项比较有效性试验，该试验直接比较两种最有效的戒烟治疗（伐尼克兰与联合尼古丁替代治疗：每种治疗N = 475），并与活性对照药物治疗（尼古丁贴片; N = 200）进行比较。所有受试者（N = 1500）将接受至少3年的评价。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，对于继续参与者为8 - 9年。疾病风险的生物标志物将集中在CVD标志物（例如，颈动脉厚度、动脉僵硬度、压力测试、炎症），包括对心血管疾病所有主要风险因素的测量。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，并确定病因（即，动脉粥样硬化进展、动脉硬化和氧化应激）的不良吸烟相关健康事件。总之，这项研究将产生关于吸烟治疗，吸烟相关疾病机制，戒烟益处以及识别最有可能发生不良心血管疾病或其他健康事件的吸烟者的重要新数据。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。 公共卫生相关性：两种有效性证据最强的戒烟药物治疗从未被直接比较过。这项研究将确定这两种治疗方法在头对头试验中的有效性如何比较，以及哪种类型的吸烟者从中受益最多。此外，许多关于吸烟和健康的数据来自多年前的研究。今天的吸烟者在许多方面与早期吸烟者不同，这些方面可能会影响吸烟对健康的影响（例如，体重、性别、饮食、社会经济地位）;拟议的工作将确定戒烟如何影响当今吸烟者的心血管和肺部健康。

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. PUBLIC HEALTH RELEVANCE: The two smoking cessation medication treatments with the strongest evidence of effectiveness have never been directly compared. This research will determine how these two treatments compare in effectiveness in a head-to-head trial, and which types of smokers benefit most from each. Also, much of the data on smoking and health come from studies from many years ago. Today's smokers differ from earlier smokers in many ways that could influence the impact of smoking on health (e.g., weight, sex, diet, socio-economic status); the proposed work will determine how smoking cessation affects cardiovascular and pulmonary health in today's smokers.