LEVEL OF ACE INHIBITION IN HEART FAILURE

该项目将评估血管紧张素转换酶(ACE)抑制对因收缩功能障碍而导致的慢性心力衰竭患者的临床和神经激素效应。这项研究的终点是对血管紧张素转换酶抑制剂治疗的反应的变异性，以及全剂量血管紧张素转换酶抑制剂达到的血管紧张素转换酶抑制水平对死亡率和是否需要辅助药物治疗的预测价值。这项为期4年的前瞻性研究将分为三个部分(1、2、3)，在这三个部分中，心力衰竭患者(1)和慢性治疗患者(2)将以随机、双盲方式被分配到使用ACE抑制剂、血管紧张素II受体拮抗剂及其组合进行治疗。退出联合治疗的血管紧张素转换酶抑制剂将检查两种药物在联合治疗中各自的作用(3)。将连续进行功能能力和神经激素激活以及对治疗反应的测量。因此，ACE逃逸现象将被证实或排除。候选人乌尔里希·乔德博士是阿尔伯特·爱因斯坦医学院心脏病学的三年级研究员，在他的导师蒂埃里·H·勒杰姆特尔博士的指导下进行了初步研究。这些初步研究结果将在即将举行的美国心脏协会科学会议上公布，表明对慢性血管紧张素转换酶抑制剂治疗的反应有很大的变异性，大多数心力衰竭患者使用全剂量血管紧张素转换酶抑制剂时只有部分血管紧张素转换酶抑制作用，加上血管紧张素转换酶抑制剂可能会得到改善。这些数据还强烈质疑ACE逃生的存在。乔德博士一直致力于以患者为中心的临床研究，并将从1999年7月起担任心脏病科的讲师，从事独立临床研究人员的职业生涯。LeJemtel博士在美国培养了一些在临床心力衰竭方面最有成效的研究人员，他同意在整个奖项期间继续担任他的导师。该提案包括AECOM已经实施的为期两年的临床研究方法学和伦理学方面的正式培训。

This project will evaluate the clinical and neurohormonal effects of Angiotensin converting-enzyme (ACE) inhibition in patients with chronic heart failure due to systolic dysfunction. Endpoints of the study are variability in the response to ACE inhibitor treatment and the predictive value of the level of ACE inhibition achieved with full dose ACE inhibitor for mortality and need for adjunctive pharmacological therapy. The prospective, 4-year study will have three parts (1,2,3) in which heart failure patients naive to ACE-inhibition (1) and patients on chronic therapy (2) will be assigned in a randomized, double blind fashion to treatment with ACE-inhibitor, Angiotensin II receptor antagonist, and their combination. Withdrawal of ACE inhibitor from the combination therapy will be done to examine the respective roles of both agents in this combination (3). Measurements of functional capacity and neurohormonal activation and response to therapy will be done serially. Thus, the phenomenon of ACE escape will be substantiated or excluded. The candidate, Dr. Ulrich Jorde, is a third year fellow in Cardiology at the Albert Einstein College of Medicine and has performed preliminary research under the guidance of his mentor, Dr. Thierry H. LeJemtel. These preliminary findings will be presented at the upcoming American Heart Association Scientific Session and indicate wide variability in the response to chronic ACE inhibitor therapy, only partial ACE inhibition in the majority of heart failure patients on full dose ACE inhibitor, and potential for improvement with addition of an ARB. The data also strongly questions the existence of ACE escape. Dr. Jorde has shown a strong commitment to patient oriented clinical research and will assume the position of an Instructor in the Division of Cardiology as of 7/99 to pursue a career as an independent clinical investigator. Dr. LeJemtel, who has trained some of the most productive researchers in clinical heart failure in the United States, has agreed to continue his mentorship throughout this award. The proposal includes a two year formal training in methodology and ethics of clinical research already in place at AECOM.