Struthers Allan D
Division of Medicine and Therapeutics, Ninewells Hospital and Medical School, Dundee, DD1 9SY, UK.
J Renin Angiotensin Aldosterone Syst. 2004 Sep;5 Suppl 1:S23-7. doi: 10.3317/jraas.2004.021.
Aldosterone plays a key role in the pathophysiology of heart failure. Angiotensin converting enzyme inhibitors and angiotensin II receptor blockers may not suppress aldosterone production in the long term. This allows aldosterone to exert its effects on myocardial fibrosis and cardiac remodelling, endothelial function, electrolytes and baroreceptor response. The Randomized Aldactone Evaluation Study (RALES) tested spironolactone against placebo in patients with severe heart failure. The study found a 30% reduction in the risk of death among patients treated with spironolactone and a 31% reduction in the risk of death from cardiac causes. Patients in the spironolactone group had significantly lower risks of death from progression of heart failure and sudden cardiac death. The Eplerenone Post-Acute Myocardial Infarction Heart Failure Efficacy and Survival Study (EPHESUS) investigated the effects of eplerenone against placebo in patients with myocardial infarction complicated by left ventricular dysfunction. Compared to placebo, the relative risk of death from any cause was 0.85 in eplerenone-treated patients, and the relative risk of death or hospitalisation for cardiovascular events was 0.87. The reduction in the risk of sudden death from cardiac causes was statistically significant. In conclusion, aldosterone blockade should form part of optimal therapy for patients with heart failure.
醛固酮在心力衰竭的病理生理学中起关键作用。长期来看,血管紧张素转换酶抑制剂和血管紧张素II受体阻滞剂可能无法抑制醛固酮的生成。这使得醛固酮能够对心肌纤维化和心脏重塑、内皮功能、电解质及压力感受器反应产生影响。随机醛固酮评估研究(RALES)对重度心力衰竭患者使用螺内酯与安慰剂进行了对比试验。该研究发现,使用螺内酯治疗的患者死亡风险降低了30%,心源性死亡风险降低了31%。螺内酯组患者因心力衰竭进展和心源性猝死的死亡风险显著更低。依普利酮急性心肌梗死后心力衰竭疗效和生存研究(EPHESUS)对心肌梗死合并左心室功能不全的患者使用依普利酮与安慰剂的效果进行了研究。与安慰剂相比,依普利酮治疗患者的任何原因导致的死亡相对风险为0.85,心血管事件导致的死亡或住院相对风险为0.87。心源性猝死风险的降低具有统计学意义。总之,醛固酮阻断应成为心力衰竭患者最佳治疗方案的一部分。