EFFECT OF MINERALOCORTICOID RECEPTOR BLOCKER, ESAXERENONE, ON NOCTURNAL HYPERTENSION: A POST HOC ANALYSIS OF ESAX-HTN STUDY

Abstract

Objective: Nocturnal hypertension is an important phenotype of abnormal diurnal blood pressure variability and a known risk marker for target organ damage and cardiovascular events. Esaxerenone is a novel, first non-steroidal mineralocorticoid receptor blocker (MRB) with a dose-dependent antihypertensive effect. We investigated the efficacy of esaxerenone on nocturnal hypertension in Japanese hypertensive patients. Design and method: The ‘Esaxerenone compared to Eplerenone in Patients with Essential Hypertension (ESAX-HTN)’ study was a phase 3, multicenter, randomized, controlled, double-blind, and parallel-group clinical study conducted in Japan. Patients were eligible for enrolment in the study if they had trough systolic BP (SBP) > = 140 and < 180 mmHg, trough diastolic BP (DBP) > = 90 and < 110 mmHg, 24-hour mean BP (ABPM) > = 130/80 mmHg. This post hoc analysis used ABPM data to evaluate the effects of esaxerenone and eplerenone on nocturnal blood pressure in patients with essential hypertension. Results: Patients (n = 1001) were randomized to esaxerenone 2.5 mg/day (n = 331) or 5 mg/day (n = 338), or eplerenone 50 mg/day (n = 332). Esaxerenone significantly lowered blood pressure from baseline throughout the 24-hour dosing interval; reductions in nighttime systolic blood pressure (95% confidence interval [CI]) were significantly greater with 2.5 and 5 mg/day esaxerenone versus eplerenone (-2.6 mmHg [-5.0, -0.2] and -6.4 mmHg [-8.8, -4.0], respectively). Esaxerenone 2.5 and 5 mg/day significantly reduced nighttime blood pressure from baseline compared with eplerenone in non-dipper patients (-4.4 mmHg [-8.6, -0.2] and -10.8 mmHg [-15.0, -6.7], respectively). In addition, esaxerenone did not markedly alter nighttime blood pressure in extreme dipper patients. In the esaxerenone 5 mg/day group, esaxerenone-induced decreases in nighttime blood pressure were greater than eplerenone-induced decreases in older patients. Conclusions: Esaxerenone may be an effective treatment option for nocturnal hypertension, especially in older patients and those with non-dipping patterns of nocturnal blood pressure.