LEVEL OF ACE INHIBITION IN HEART FAILURE

心力衰竭时的 ACE 抑制水平

• 批准号: 6183157
• 负责人: ULRICH P JORDE
• 金额: $ 12.91万
• 依托单位: COLUMBIA UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-09-30 至 2004-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6183157
• 关键词: ACE inhibitors; angiotensin receptor; clinical research; combination chemotherapy; heart contraction; heart disorder chemotherapy; heart failure; human subject; human therapy evaluation; inhibitor /antagonist

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.

本项目将评估血管紧张素转换酶（ACE）抑制在因收缩功能障碍引起的慢性心力衰竭患者中的临床和神经激素效应。该研究的终点是对ACE抑制剂治疗反应的可变性，以及全剂量ACE抑制剂达到的ACE抑制水平对死亡率和辅助药物治疗需求的预测价值。这项为期4年的前瞻性研究将分为三部分（1,2,3），其中首次接受ace抑制的心力衰竭患者(1)和正在接受慢性治疗的患者(2)将以随机、双盲的方式被分配到ace抑制剂、血管紧张素II受体拮抗剂及其联合治疗组。将从联合治疗中退出ACE抑制剂，以检查两种药物在联合治疗中的各自作用(3)。功能容量、神经激素激活和治疗反应的测量将依次进行。从而证实或排除ACE逸出现象。候选人乌尔里希·约德（Ulrich Jorde）博士是阿尔伯特·爱因斯坦医学院（Albert Einstein College of Medicine）心脏病学专业的三年级研究员，他在导师蒂埃里·h·勒杰特尔（Thierry H. LeJemtel）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发表，并表明慢性ACE抑制剂治疗的反应存在广泛的可变性，大多数心力衰竭患者在全剂量ACE抑制剂治疗中只有部分ACE抑制，并且在添加ARB后可能会改善。数据也强烈质疑ACE逃逸的存在。Jorde博士一直致力于以患者为导向的临床研究，并将于1999年7月担任心脏病学部门的讲师，以追求独立临床研究者的职业生涯。LeJemtel博士在美国培训了一些最有成效的临床心力衰竭研究人员，他同意在整个奖项期间继续担任他的导师。该提议包括在AECOM已经到位的临床研究方法和伦理方面进行为期两年的正式培训。