CLINICAL MANAGEMENT OF NICOTINIC ACID--CREATING A MODEL

已经发现用烟酸治疗对以下病症高度有效： 降低总胆固醇、低密度脂蛋白 胆固醇，甘油三酯，也许脂蛋白Lp（a），提高 高密度脂蛋白胆固醇水平，并降低死亡率 冠心病和总死亡率。 一个重要 烟酸疗法的缺点是， 系统评价副作用（恶心，视力模糊， 皮肤潮红）和内科并发症（糖尿病，消化性溃疡， 痛风性关节炎，肝功能障碍）， 使用. 因此，临床医生缺乏烟酸可以作为 安全有效地管理。 我们建议对尼古丁的管理进行深入的评估， 酸 来自冠状动脉药物项目的数据-一项为期6年的，双盲， 1119名男性使用烟酸的随机对照临床试验 --已经获得，并将成为主要的信息来源。 每4个月评估一次入组本试验的受试者; 肝功能、糖耐量和血脂水平的变化。 获得，并进行全面的体格检查和治疗侧评估 效果进行。 本提案的主要目的是确定和描述 与副作用和医疗发展相关的关键变量 并发症，并使用这些信息来制定临床管理 模型 每种生化变量的变化模式 兴趣（例如，天冬氨酸氨基转移酶的血液水平，碱性 磷酸酶、葡萄糖、尿酸、总胆固醇、甘油三酯）将 并在安慰剂和治疗之间进行比较 队列来表征对烟酸的毒性反应。 然后 搜索变量（例如，年龄、身体、体重、其他医疗状况） 预测生化参数的异常变化 进行。最后，逻辑回归方法将用于1）开发 预测哪些患者易患并发症的模型 由于烟酸的使用，因此可以避免治疗， 2）确定哪些变量是即将发生的事件的早期预测因子 毒性反应，因此可以适当修改治疗。 烟酸目前比洛伐他汀便宜16倍， 疗效相当的血脂异常药物。 以其示范 效率和成本效益的记录，消除最后的障碍， 烟酸在适当患者中的广泛使用- 医生对有效管理缺乏信心， 是治疗血脂异常的重要工具， 对心脏病死亡率产生有益影响。

Treatment with nicotinic acid has been found to be highly effective for lowering levels of total cholesterol, low-density lipoprotein cholesterol, triglycerides, and perhaps lipoprotein Lp (a), raising levels of high-density lipoprotein cholesterol, and reducing mortality from coronary heart disease as well as total mortality. An important drawback of nicotinic acid therapy is that there has not yet been a systematic appraisal of the side effects (nausea, blurred vision, cutaneous flushing) and medical complications (diabetes, peptic ulcer, gouty arthritis, liver dysfunction) that have been associated with its use. Thus, clinicians lack the conviction that nicotinic acid can be safely and effectively managed. We propose to perform an indepth appraisal of the management of nicotinic acid. Data from the Coronary Drug Project -- a 6-year, double-blind, randomized, controlled clinical trial of nicotinic acid use in 1119 males -- have been obtained and will be the major source of information. Subjects enrolled in this trial were assessed every 4 months; measures of liver function, glucose tolerance, and levels of blood lipids were obtained, and a thorough physical exam and assessment of treatment side effects conducted. The primary objective of this proposal is to identify and characterize key variables associated with the development of side effects and medical complications, and use this information to develop a clinical management model. Patterns of change for each of the biochemical variables of interest (e.g., blood levels of aspartate amino transferase, alkaline phosphatase, glucose, uric acid, total cholesterol, triglycerides) will be determined and comparisons made between the placebo and treatment cohorts to characterize the toxic response to nicotinic acid. Then, a search for variables (e.g., age, body, weight, other medical conditions) that predict abnormal changes in the biochemical parameters will be conducted. Finally, logistic regression methods will be used to 1) develop models that predict which patients have a susceptibility to complications arising from nicotinic acid use, so treatment can be avoided in those, and 2) determine which variables are early predictors of an impending toxic response, so treatment can be appropriately modified. Nicotinic acid is presently sixteen times less expensive than lovastatin, a dyslipidemia drug with comparable efficacy. With its demonstrated record of efficacy and cost-effectiveness, removing the last obstacle for widespread use of nicotinic acid in appropriate patients -- the physician's lack of confidence in effective management -- would provide an important tool for the treatment of dyslipidemia, and consequently have a beneficial impact upon rates of heart disease mortality.