Department of Internal Medicine III-Cardiology, Angiology and Intensive Care Medicine, Homburg University Hospital, Saarland University, Kirrberger Str. 100, Homburg 66424, Germany.
Department of Cardiology, University Heart Center Basel, University Hospital Basel, Am Petersgraben 4, Basel 4031, Switzerland.
Eur Heart J Cardiovasc Pharmacother. 2024 Oct 4;10(6):557-565. doi: 10.1093/ehjcvp/pvae049.
Steroidal mineralocorticoid receptor antagonists (MRAs) bind to the mineralocorticoid receptor and antagonize the effects of aldosterone, which contributes to the development and progression of cardio- and renovascular diseases. Guidelines recommend steroidal MRAs in patients with heart failure with reduced or mildly reduced ejection fraction, as they reduce morbidity and mortality. In heart failure with preserved ejection fraction, MRAs have not convincingly shown to improve prognosis. Steroidal MRAs delay the progression of chronic kidney disease, reduce proteinuria and lower blood pressure in resistant hypertension but can induce hyperkalaemia. Due to their limited selectivity to the mineralocorticoid receptor, steroidal MRAs can cause significant adverse effects, i.e. libido loss, erectile dysfunction, gynaecomastia, and amenorrhoea, leading to low rates of persistance. Against this background, new avenues for developing non-steroidal, selective (ns)MRAs and aldosterone-synthase inhibitors have been taken. Finerenone has been shown to delay the progression of diabetic nephropathy and lower the incidence of heart failure hospitalizations in patients with chronic kidney disease and diabetes compared with placebo. Finerenone has therefore been recommended by the 2023 European Society of Cardiology Guidelines for the management of diabetes in patients with type 2 diabetes and chronic kidney disease. Further randomized controlled trials assessing the safety and effectiveness of finerenone in patients with heart failure are currently ongoing. Esaxerenone provides antihypertensive effects and has been approved for the treatment of hypertension in Japan. Baxdrostat and lorundostat, novel selective aldosterone-synthase inhibitors, are currently under investigation. In phase II trials, baxdrostat and lorundostat were safe and effective in lowering blood pressure in resistant hypertension. In this review, we summarize and critically discuss the evidence for new drugs mitigating aldosterone in heart failure, hypertension, and chronic kidney disease.
甾体类盐皮质激素受体拮抗剂（MRA）与盐皮质激素受体结合，拮抗醛固酮的作用，醛固酮促进了心血管和肾脏疾病的发生和进展。指南建议在心衰射血分数降低或轻度降低的患者中使用甾体类 MRA，因为它们降低了发病率和死亡率。在心衰射血分数保留的患者中，MRA 并未令人信服地显示出改善预后的作用。甾体类 MRA 可延缓慢性肾脏病的进展，减少抵抗性高血压患者的蛋白尿和降低血压，但可引起高钾血症。由于其对盐皮质激素受体的选择性有限，甾体类 MRA 可引起显著的不良反应，如性欲丧失、勃起功能障碍、男性乳房发育和闭经，导致坚持治疗的比例较低。在此背景下，开发非甾体、选择性（ns）MRA 和醛固酮合酶抑制剂的新途径已经出现。非奈利酮已被证明可延缓糖尿病肾病的进展，并降低慢性肾脏病和糖尿病患者心力衰竭住院的发生率，与安慰剂相比。因此，2023 年欧洲心脏病学会指南建议在 2 型糖尿病和慢性肾脏病患者中使用非奈利酮来管理糖尿病。目前正在进行评估非奈利酮在心力衰竭患者中的安全性和有效性的随机对照试验。依普利酮可提供降压作用，已在日本获准用于高血压治疗。新型选择性醛固酮合酶抑制剂 baxdrostat 和 lorundostat 目前正在研究中。在 II 期试验中，baxdrostat 和 lorundostat 在降低抵抗性高血压患者的血压方面是安全有效的。在这篇综述中，我们总结并批判性地讨论了新药物减轻心力衰竭、高血压和慢性肾脏病中醛固酮作用的证据。
