POSTMENOPAUSAL HORMONE THERAPY IN UNSTABLE ANGINA

不稳定型心绞痛的绝经后激素治疗

• 批准号: 6030667
• 负责人: Steven Paul Schulman
• 金额: $ 27.63万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1995
• 资助国家: 美国
• 起止时间: 1995-07-01 至 2000-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6030667
• 关键词: angina pectoris; cardiovascular stress test; clinical trials; combination chemotherapy; electrocardiography; estrogens; female; heart disorder chemotherapy; hormone therapy; human subject; human therapy evaluation; intravenous administration; myocardial ischemia /hypoxia; oral administration; postmenopause; progesterone; statistics /biometry; women's health

Unstable angina is a frequent diagnosis in post-menopausal women and is associated with a significant risk of myocardial infarction and need for revascularization. The pathogenesis of unstable angina involves vasoconstriction superimposed on fixed disease causing a temporary decrease in coronary blood flow. Recent catheterization studies in patients with atherosclerosis utilizing quantitative angiography and intracoronary doppler measurements of blood flow velocity suggest that endothelial dysfunction results in a paradoxical coronary vasoconstriction response to certain neurohumoral stimuli including acetylcholine, catecholamines and serotonin and resultant myocardial ischemia. Therapeutic agents which prevent or limit this vasoconstriction may prevent recurrent ischemia and/or myocardial infarction in unstable angina patients. Recently, estrogen receptors were identified in the smooth muscle of post-mortem human coronary arteries. Work in animal models and studies in post-menopausal women suggest that intravenous estrogen acutely decreases coronary vascular resistance, increases coronary blood flow and prevents the paradoxical response to acetylcholine in patients with endothelial dysfunction. This randomized double-blind placebo controlled study tests the hypothesis that the addition of intravenous followed by oral estrogen and of the combination of intravenous and oral estrogen and progesterone to the routine management of unstable angina are beneficial compared with placebo in post-menopausal women. Post-menopausal women with rest angina and no contraindications to hormone therapy will be randomized to receive one of three drug treatment groups, in addition to routine management including intravenous nitroglycerin, aspirin, and heparin. Patients will remain on study drug for three weeks. Initial endpoints during the hospitalization will include ischemia detected on 48 hours of continuous electrocardiographic monitoring, and clinical endpoints of myocardial infarction, death, and need for revascularization. Patients will undergo exercise stress testing and 48 hour monitoring at three weeks and ten days following withdrawal of the study drug.

不稳定型心绞痛是绝经后妇女的常见诊断，并且 与心肌梗塞的显着风险相关，并且需要 血运重建。 不稳定型心绞痛的发病机制包括 血管收缩叠加在固定疾病上，导致暂时性的 冠状动脉血流量减少。最近的导管插入术研究 动脉粥样硬化患者利用定量血管造影术 冠状动脉内多普勒血流速度测量表明 内皮功能障碍导致矛盾的冠状血管收缩 对某些神经体液刺激（包括乙酰胆碱）的反应， 儿茶酚胺和血清素以及由此导致的心肌缺血。 预防或限制这种血管收缩的治疗剂可能会 预防不稳定型心绞痛中的复发性缺血和/或心肌梗塞 患者。最近，在平滑肌中发现了雌激素受体。 死后人类冠状动脉的肌肉。从事动物模型和 对绝经后妇女的研究表明，静脉注射雌激素可显着 降低冠状血管阻力，增加冠状动脉血流量 防止患者对乙酰胆碱的矛盾反应 内皮功能障碍。 这项随机双盲安慰剂对照研究检验了这一假设 静脉注射雌激素后口服雌激素 静脉注射和口服雌激素和孕激素的组合 与安慰剂相比，不稳定心绞痛的常规治疗是有益的 在绝经后妇女中。绝经后妇女患有静息心绞痛且无 有激素治疗禁忌症的患者将被随机分配接受其中一种治疗 三个药物治疗组，除了常规管理外，还包括 静脉注射硝酸甘油、阿司匹林和肝素。 患者将继续 研究药物三周。 住院期间的初始终点 将包括连续 48 小时检测到的缺血 心电图监测和心肌的临床终点 梗塞、死亡和需要血运重建。患者将经历 三周零十天的运动压力测试和48小时监测 停用研究药物后。

项目成果

Effects of acute hormone therapy on recurrent ischemia in postmenopausal women with unstable angina.

急性激素治疗对患有不稳定心绞痛的绝经后妇女复发性缺血的影响。

• DOI: 10.1016/s0735-1097(01)01724-7
• 发表时间: 2002
• 期刊: Journal of the American College of Cardiology
• 影响因子: 24
• 作者: Schulman,StevenP;Thiemann,DavidR;Ouyang,Pamela;Chandra,NishaC;Schulman,DouglasS;Reis,StevenE;Terrin,Michael;Forman,Sandra;deAlbuquerque,CiceroPiva;Bahr,RaymondD;Townsend,SusanN;Cosgriff,Rosalie;Gerstenblith,Gary
• 通讯作者: Gerstenblith,Gary

Effect of short-term estrogen with and without progesterone therapy on circulating markers of endothelial activation and injury in postmenopausal women with unstable angina pectoris.

短期雌激素加或不加黄体酮治疗对患有不稳定心绞痛的绝经后妇女内皮激活和损伤的循环标志物的影响。

• DOI: 10.1016/s0002-9149(03)00273-x
• 发表时间: 2003
• 期刊: The American journal of cardiology
• 作者: Chou,EricT;Schulman,StevenP;Thiemann,DavidR;Sohn,RichardH;Bellantoni,MicheleF;Rade,JeffreyJ
• 通讯作者: Rade,JeffreyJ