landmark clinical trials focusing on aldosterone antagonists (mineralocorticoid receptor antagonists) like spironolactone and eplerenone, which are commonly used in heart failure and other conditions:
1. RALES (1999)
• Title: Randomized Aldactone Evaluation Study
• Focus: Heart failure with reduced ejection fraction (HFrEF).
• Key Finding: Spironolactone reduced mortality by 30% and hospitalizations by 35% in patients with severe HFrEF (NYHA class III-IV).
• Published In: The New England Journal of Medicine (NEJM).
2. EPHESUS (2003)
• Title: Eplerenone Post-Acute Myocardial Infarction Heart Failure Efficacy and Survival Study
• Focus: Post-MI patients with heart failure and reduced ejection fraction.
• Key Finding: Eplerenone reduced all-cause mortality by 15% and cardiovascular death by 21%.
• Published In: NEJM.
3. TOPCAT (2014)
• Title: Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist
• Focus: Heart failure with preserved ejection fraction (HFpEF).
• Key Finding: Spironolactone reduced HF-related hospitalizations but did not significantly reduce overall mortality. Subgroup analyses revealed possible regional variations in benefit.
• Published In: NEJM.
4. AMBER (2019)
• Title: Spironolactone in Resistant Hypertension and Chronic Kidney Disease
• Focus: Resistant hypertension in patients with CKD.
• Key Finding: Spironolactone improved blood pressure control without significantly worsening hyperkalemia.
• Published In: The Lancet.
5. PATHWAY-2 (2015)
• Title: Optimal Treatment for Resistant Hypertension
• Focus: Resistant hypertension.
• Key Finding: Spironolactone was the most effective add-on therapy for resistant hypertension compared to other options like bisoprolol or doxazosin.
• Published In: The Lancet.