Davis Kelli L, Nappi Jean M
College of Pharmacy, Medical University of South Carolina, Charleston, South Carolina 29425, USA.
Clin Ther. 2003 Nov;25(11):2647-68. doi: 10.1016/s0149-2918(03)80326-0.
The role of the renin-angiotensin-aldosterone system in the pathophysiology and treatment of hypertension and heart failure has been extensively studied. Angiotensin-converting enzyme inhibitors and angiotensin II-receptor blockers have been shown to effectively reduce blood pressure, protect the kidney, and reduce morbidity and mortality in patients with heart failure. Therefore, there is increased interest in the effects of aldosterone and the use of aldosterone-receptor antagonists in the treatment of cardiovascular disease. Eplerenone is the first selective aldosterone-receptor antagonist approved for the treatment of hypertension and left ventricular (LV) dysfunction after acute myocardial infarction (AMI).
The goal of this article was to review the pharmacologic properties, clinical efficacy, and tolerability of eplerenone in the treatment of hypertension, LV dysfunction, and proteinuria.
Relevant English-language articles were identified through searches of MEDLINE (1966-May 2003), Current Contents, and International Pharmaceutical Abstracts (1970-May 2003) using the terms hypertension, heart failure, eplerenone, aldosterone, and aldosterone antagonist. Other pertinent publications were identified from the reference lists of the identified articles. Information was also obtained from abstracts presented at national meetings and data on file with the manufacturer.
In clinical trials, eplerenone alone and in combination with renin-angiotensin blockade significantly reduced both systolic and diastolic blood pressure compared with placebo (P < 0.05 to P < 0.001). In EPHESUS (Eplerenone Post-Acute Myocardial Infarction Heart Failure Efficacy and Survival Study), the addition eplerenone to optimal medical therapy reduced morbidity and mortality in patients with AMI and LV dysfunction, although the incidence of serious hyperkalemia was also significantly greater. In comparisons with spironolactone, eplerenone was associated with a lower incidence of gynecomastia and other sex hormone-related adverse effects.
Either alone or in combination with other antihypertensive agents, eplerenone appears to be effective for the treatment of hypertension. Morbidity and mortality were reduced when eplerenone was added to standard therapy for LV dysfunction complicating AMI. The use of eplerenone for hypertension or heart failure may be limited in patients at risk for hyperkalemia.
肾素 - 血管紧张素 - 醛固酮系统在高血压和心力衰竭的病理生理学及治疗中的作用已得到广泛研究。血管紧张素转换酶抑制剂和血管紧张素II受体阻滞剂已被证明能有效降低血压、保护肾脏并降低心力衰竭患者的发病率和死亡率。因此，人们对醛固酮的作用以及醛固酮受体拮抗剂在心血管疾病治疗中的应用兴趣日益增加。依普利酮是首个被批准用于治疗高血压以及急性心肌梗死（AMI）后左心室（LV）功能障碍的选择性醛固酮受体拮抗剂。
本文旨在综述依普利酮在治疗高血压、左心室功能障碍和蛋白尿方面的药理特性、临床疗效及耐受性。
通过检索MEDLINE（1966年 - 2003年5月）、《现刊目次》和《国际药学文摘》（1970年 - 2003年5月），使用高血压、心力衰竭、依普利酮、醛固酮和醛固酮拮抗剂等检索词，确定相关英文文章。从已确定文章的参考文献列表中找出其他相关出版物。还从在全国会议上发表的摘要以及制造商存档的数据中获取信息。
在临床试验中，与安慰剂相比，单独使用依普利酮以及与肾素 - 血管紧张素阻滞剂联合使用均能显著降低收缩压和舒张压（P < 0.05至P < 0.001）。在EPHESUS（依普利酮急性心肌梗死后心力衰竭疗效和生存研究）中，在最佳药物治疗基础上加用依普利酮可降低AMI和左心室功能障碍患者的发病率和死亡率，尽管严重高钾血症的发生率也显著更高。与螺内酯相比，依普利酮与男性乳房发育及其他与性激素相关的不良反应发生率较低有关。
依普利酮单独使用或与其他抗高血压药物联合使用似乎对治疗高血压有效。在标准治疗基础上加用依普利酮可降低AMI并发左心室功能障碍患者的发病率和死亡率。对于有高钾血症风险的患者，依普利酮用于高血压或心力衰竭的治疗可能会受到限制。
