de Denus S, Leclair G, Dubé MP, et al. - Given that no improvement in efficacy endpoints was achieved with high‐dose spironolactone (100 mg daily) over usual care [placebo or continued low‐dose spironolactone (25 mg daily) among patients already taking spironolactone] in the treatment of acute heart failure (HF) in ATHENA‐HF (Aldosterone Targeted Neurohormonal Combined with Natriuresis Therapy in Heart Failure), researchers investigated whether low levels 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 outcomes. Findings revealed the presence of lower‐than‐anticipated levels of spironolactone active metabolites in the high‐dose spironolactone group for at least 48 h and these were suggested to have possibly contributed to the lack of pharmacological impacts of spironolactone in the ATHENA‐HF trial.