A Prospective Crossover Clinical Trial of Esaxerenone and Eplerenone in Patients with Chronic Heart Failure Complicated by Hypertension

Esaxerenone, which blocks aldosterone binding, is approved to treat hypertension but not heart failure. We aimed to understand esaxerenone's efficacy in treating chronic heart failure. This crossover study compared esaxerenone with eplerenone, an approved treatment for heart failure, in 66 patients with chronic heart failure complicated by hypertension (12 months for each drug). The primary endpoint was brain natriuretic peptide. The secondary endpoints included blood pressure; hormones and enzymes that regulate electrolytes and stress response; and biomarkers of kidney function. Change in brain natriuretic peptide concentration was significantly lower for esaxerenone compared with eplerenone at 3, 6, and 12 months. Blood pressure (all time points), plasma aldosterone concentration (3 and 6 months), and urinary albumin-to-creatinine ratio (3 and 6 months) were significantly lower for esaxerenone compared with eplerenone. The results suggest that esaxerenone more strongly blocks aldosterone binding than does eplerenone. This effect, together with its strong antihypertensive effect and reduced urinary albumin-to-creatinine ratio, suggests that esaxerenone improves kidney function. The results of this small-scale, single-center study need to be expanded to a larger-scale investigation, but esaxerenone shows promise as a treatment for chronic heart failure with hypertension.