Sethi Rishi, Vishwakarma Pravesh, Pradhan Akshyaya
Department of Cardiology, King George's Medical University Uttar Pradesh, India.
Card Fail Rev. 2024 Nov 12;10:e15. doi: 10.15420/cfr.2024.10. eCollection 2024.
Activation of the renin-angiotensin-aldosterone system is the ultimate pathophysiological hallmark in heart failure. Though aldosterone primarily appears to regulate electrolyte homeostasis by acting on distal nephrons in the kidneys, its effects are far-reaching across the cardiovascular system as its receptors are also expressed in vascular smooth muscle cells, endothelial cells, macrophages and cardiomyocytes. Aldosterone excess leads to vascular stiffness, vasoconstriction, endothelial dysfunction, inflammation, oxidative stress, cardiac fibrosis and hypertrophy, atherogenesis and thrombosis. Hence, aldosterone antagonism is an attractive proposition for heart failure management. The first-generation non-selective mineralocorticoid receptor antagonist spironolactone produced a spectacular reduction of cardiovascular outcomes in the seminal RALES study, while the selective second-generation congener eplerenone boasts two positive studies: EPHESUS and EMPHASIS-HF. The TOPCAT trial indicated that a specific subgroup of patients with heart failure with preserved ejection fraction may benefit from targeted therapy of mineralocorticoid receptor antagonists. Newer-generation non-steroidal mineralocorticoid antagonists and aldosterone synthase inhibitors are being evaluated in randomised trials.
肾素-血管紧张素-醛固酮系统的激活是心力衰竭最终的病理生理标志。尽管醛固酮主要通过作用于肾脏远曲小管来调节电解质平衡，但其影响在心血管系统中广泛存在，因为其受体也表达于血管平滑肌细胞、内皮细胞、巨噬细胞和心肌细胞中。醛固酮过多会导致血管僵硬、血管收缩、内皮功能障碍、炎症、氧化应激、心脏纤维化和肥大、动脉粥样硬化形成和血栓形成。因此，醛固酮拮抗作用是心力衰竭治疗中一个有吸引力的方法。第一代非选择性盐皮质激素受体拮抗剂螺内酯在具有里程碑意义的RALES研究中显著降低了心血管事件的发生率，而选择性第二代同类药物依普利酮则有两项阳性研究：EPHESUS研究和EMPHASIS-HF研究。TOPCAT试验表明，射血分数保留的心力衰竭患者的一个特定亚组可能从盐皮质激素受体拮抗剂的靶向治疗中获益。新一代非甾体盐皮质激素拮抗剂和醛固酮合酶抑制剂正在随机试验中进行评估。
