Spironolactone metabolite concentrations in decompensated heart failure: insights from the ATHENA‐HF trial

ABSTRACT Aims In Aldosterone Targeted Neurohormonal Combined with Natriuresis Therapy in Heart Failure (ATHENA‐HF), high‐dose spironolactone (100 mg daily) did not improve efficacy endpoints over usual care [placebo or continued low‐dose spironolactone (25 mg daily) in patients already receiving spironolactone] in the treatment of acute heart failure (HF). We hypothesized that low concentrations of the long‐acting active metabolites of spironolactone [canrenone and 7α‐thiomethylspironolactone (7α‐TMS)] in the high‐dose group could have contributed to these neutral results. Methods and results In patients randomized to high‐dose spironolactone not previously treated with spironolactone (high‐dose‐naïve, n = 112), concentrations of canrenone and 7α‐TMS increased at 48 and 96 h compared to baseline, and between 48 and 96 h (all P