LEVEL OF ACE INHIBITION IN HEART FAILURE

本项目将评估血管紧张素转换酶（ACE）抑制剂对收缩功能障碍所致慢性心力衰竭患者的临床和神经激素影响。研究的终点是对ACE抑制剂治疗反应的变异性和全剂量ACE抑制剂达到的ACE抑制水平对死亡率和连续药物治疗需求的预测值。这项前瞻性、4年研究将分为三个部分（1、2、3），其中ACE抑制剂初治的心力衰竭患者（1）和长期治疗患者（2）将以随机、双盲方式被分配接受ACE抑制剂、血管紧张素II受体拮抗剂及其联合治疗。 将从联合治疗中停用ACE抑制剂，以检查两种药物在联合治疗中的各自作用（3）。将连续测量功能能力和神经激素激活以及对治疗的反应。 因此，ACE逃逸现象将得到证实或排除。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，并在他的导师蒂埃里·H。勒杰姆特尔 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，并表明对慢性ACE抑制剂治疗的反应存在很大差异，在大多数接受全剂量ACE抑制剂治疗的心力衰竭患者中仅部分ACE抑制，以及通过添加ARB改善的潜力。 这些数据也强烈质疑ACE逃逸的存在。Jorde博士对以患者为导向的临床研究表现出了坚定的承诺，并将于1999年7月担任心脏病科讲师，以追求独立临床研究者的职业生涯。 LeJemtel博士曾在美国培训过一些临床心力衰竭方面最富有成效的研究人员，他已同意在整个奖项期间继续担任导师。 该提案包括在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。

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.