LEVEL OF ACE INHIBITION IN HEART FAILURE

心力衰竭时的 ACE 抑制水平

• 批准号: 6388669
• 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/6388669
• 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.

该项目将评估血管紧张素转换酶（ACE）抑制对收缩功能障碍导致的慢性心力衰竭患者的临床和神经激素影响。该研究的终点是对 ACE 抑制剂治疗反应的变异性，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个部分 (1,2,3)，其中未接受过 ACE 抑制的心力衰竭患者 (1) 和接受长期治疗的患者 (2) 将以随机、双盲的方式分配至接受 ACE 抑制剂、血管紧张素 II 受体拮抗剂及其联合治疗。 将从联合治疗中撤出 ACE 抑制剂，以检查两种药物在该联合治疗中各自的作用 (3)。功能能力、神经激素激活和治疗反应的测量将连续进行。 由此，ACE逃逸现象将得到证实或排除。候选人 Ulrich Jorde 博士是阿尔伯特·爱因斯坦医学院心脏病学三年级研究员，在导师 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召开的美国心脏协会科学会议上公布，表明对慢性 ACE 抑制剂治疗的反应存在很大差异，大多数心力衰竭患者在服用全剂量 ACE 抑制剂时仅能部分抑制 ACE，并且通过添加 ARB 可能会得到改善。 该数据还强烈质疑 ACE 逃逸的存在。 Jorde 博士表现出了对以患者为导向的临床研究的坚定承诺，并将于 7/99 起担任心脏病科讲师，从事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，他同意在整个获奖过程中继续担任他的指导。 该提案包括 AECOM 已经开展的为期两年的临床研究方法和伦理方面的正式培训。