The spironolactone renaissance

Until recently, spironolactone was considered only as an antagonist at the aldosterone receptors of the epithelial cells of the kidney and nas used cl inically in the treatment of hyperaldosteronism and, occasionally, as a K+- sparing diuretic. Tile spironolactone renaissance started with the experime ntal finding that spironolactone reversed aldosterone-induced cardiac fibro sis by a cardiac action. Experimentally, spironolactone also has direct eff ects on blood vessels. Spironolactone reduces vascular fibrosis and injury, inhibits angiogenesis. reduces vascular tone and reduces portal hypertensi on. The rationale for the Randomized Aldactone Evaluation Study (RALES) of spironolactone in heart failure was that 'aldosterone escape' occurred thro ugh non-angiotensin II mechanisms. The RALES clinical trial was stopped ear ly when it was shown that there was a 30% reduction in risk of death among the spironolactone patients. In RALES, spironolactone also reduced hospital isation for worsening heart failure and improved the symptoms of heart fail ure. Other recent clinical trials have shown that spironolactone reduces ca rdiac and vascular collagen turnover, improves heart variability, reduces v entricular arrhythmias, improves endothelial dysfunction and dilates blood vessels in human heart failure and these effects probably all contribute to the increased survival in heart failure. Spironolactone may also be useful in the treatment of left ventricular hypertrophy, portal hypertension and cirrhosis. There have also been some recent small clinical trials of spiron olactone as an anti-androgen showing potential in acne, hirsutism and preco cious puberty.