Cannon Christopher P, Dansky Hayes M, Davidson Michael, Gotto Antonio M, Brinton Eliot A, Gould A Lawrence, Stepanavage Michael, Liu Sherry Xueyu, Shah Sukrut, Rubino Joseph, Gibbons Patrice, Hermanowski-Vosatka Anne, Binkowitz Bruce, Mitchel Yale, Barter Philip
TIMI Study Group, Cardiovascular Division, Brigham and Women's Hospital, Boston, MA 02115, USA.
Am Heart J. 2009 Oct;158(4):513-519.e3. doi: 10.1016/j.ahj.2009.07.028.
Residual cardiovascular (CV) risk often remains high despite statin therapy to lower low-density lipoprotein cholesterol (LDL-C). New therapies to raise high-density lipoprotein cholesterol (HDL-C) are currently being investigated. Anacetrapib is a cholesteryl ester transfer protein (CETP) inhibitor that raises HDL-C and reduces LDL-C when administered alone or with a statin. Adverse effects on blood pressure, electrolytes, and aldosterone levels, seen with another drug in this class, have not been noted in studies of anacetrapib to date.
Determining the EFficacy and Tolerability of CETP INhibition with AnacEtrapib (DEFINE) is a randomized, double-blind, placebo-controlled trial to assess the efficacy and safety profile of anacetrapib in patients with coronary heart disease (CHD) or CHD risk equivalents (clinical trials.gov NCT00685776). Eligible patients at National Cholesterol Education Program-Adult Treatment Panel III LDL-C treatment goal on a statin, with or without other lipid-modifying medications, are treated with anacetrapib, 100 mg, or placebo for 18 months, followed by a 3-month, poststudy follow-up. The primary end points are percent change from baseline in LDL-C and the safety and tolerability of anacetrapib. Comprehensive preplanned interim safety analyses will be performed at the 6- and 12-month time points to examine treatment effects on key safety end points, including blood pressure and electrolytes. A preplanned Bayesian analysis will be performed to interpret the CV event distribution, given the limited number of events expected in this study.
A total of 2,757 patients were screened at 153 centers in 20 countries, and 1,623 patients were randomized into the trial. Lipid results, clinical CV events, and safety outcomes from this trial are anticipated in 2010.
尽管使用他汀类药物降低低密度脂蛋白胆固醇（LDL-C），残余心血管（CV）风险通常仍很高。目前正在研究提高高密度脂蛋白胆固醇（HDL-C）的新疗法。阿那曲匹布是一种胆固醇酯转运蛋白（CETP）抑制剂，单独使用或与他汀类药物联用时可提高HDL-C并降低LDL-C。迄今为止，在阿那曲匹布的研究中尚未发现该类别的另一种药物所出现的对血压、电解质和醛固酮水平的不良反应。
阿那曲匹布CETP抑制作用的疗效和耐受性测定（DEFINE）是一项随机、双盲、安慰剂对照试验，旨在评估阿那曲匹布在冠心病（CHD）或CHD风险等同症患者中的疗效和安全性（临床试验.gov NCT00685776）。符合美国国家胆固醇教育计划成人治疗专家组III LDL-C治疗目标且正在接受他汀类药物治疗（无论是否使用其他调脂药物）的合格患者，接受100 mg阿那曲匹布或安慰剂治疗18个月，随后进行3个月的研究后随访。主要终点是LDL-C相对于基线的变化百分比以及阿那曲匹布的安全性和耐受性。将在第6个月和第12个月时间点进行全面的预先计划的中期安全性分析，以检查对关键安全性终点（包括血压和电解质）的治疗效果。鉴于本研究预期的事件数量有限，将进行预先计划的贝叶斯分析以解释CV事件分布。
在20个国家的153个中心共筛选了2757例患者，1623例患者被随机纳入试验。预计2010年可得出该试验的血脂结果、临床CV事件和安全性结果。
