Implication of Mineralocorticoid Receptor Antagonist Esaxerenone in Patients With Heart Failure With Preserved Ejection Fraction

Abstract

steroidal MRA that specifically inhibits excessive mineralocorticoid receptor activity; thus far, esaxerenone is indicated only for refractory hypertension. 7 Given the evidence that other steroidal MRAs (spironolactone and eplerenone) improve prognosis in patients with HFrEF, 8-10 esaxerenone may also potentially have beneficial effects on the heart. A recent animal study demonstrated that the administration of esaxerenone reduced cardiac fibrosis, systemic inflammation, and oxidative stress in rats with salt-induced myocardial injury. 11 Taking all these findings into consideration, in the present study we investigated the effects of esaxerenone on cardiac reverse remodeling in patients with HFpEF and hypertension. Methods Patient SelectionConsecutive patients who received esaxerenone for the treatment of hypertension refractory to at least 2 antihypertensive agents between

Efficacy and Safety of Esaxerenone in Hypertensive Patients with Left Ventricular Hypertrophy (ESES-LVH) Study: A Multicenter, Open-Label, Prospective, Interventional Study

“…This similar time-dependent decline was also observed in both subcohorts. This reductive effect on LVMI is consistent with the result of a previous retrospective study, the only study to evaluate the cardioprotective effect of esaxerenone over 6 months using echocardiography in hypertensive patients with heart failure with preserved ejection fraction (HFpEF) [ 35 ]. LVH regression was also reported with the other steroidal MRBs.…”

“…The following mechanisms may underlie the marked reduction of LVMI by esaxerenone: (1) via BP reduction, (2) the pleiotropic effects of neurohormonal modulation, and (3) direct effects on myocardium. Although BP reduction is the primary mechanism, a previous report comparing the BP- and LVMI-lowering effects of esaxerenone before and after its administration suggested that the LVMI-lowering effect of esaxerenone might be also exerted by a mechanism independent of its antihypertensive effect [ 35 ]. Indeed, in the present study, the antihypertensive effect of esaxerenone reached steady state at approximately 6 weeks, whereas the LVMI-reducing effect persisted up to 24 weeks.…”

“…This observation is consistent with the 4E-left ventricular hypertrophy study, in which the effect of eplerenone (alone or in combination with enalapril) on the change in BP and its effect on reducing LVM did not move in parallel [ 47 ]. Considering these results and the fact that the LVMI-lowering effect of esaxerenone was accompanied by a decrease in plasma BNP [ 35 – 37 ], we assume pleiotropic effects through neurohormonal modulation and/or direct effects on myocardium of esaxerenone. Recently, esaxerenone was found to reduce cardiac inflammation and oxidative stress in high salt-loaded rats, leading to improvement of cardiac remodeling and the reduction of fibrosis [ 33 ].…”

“…In this study, the baseline mean LVEF value of the patients was 62.8% within the normal range; however, LVEF tended to further increase with esaxerenone treatment and was significantly increased in the RASi subcohort. The previous reports of esaxerenone in hypertensive patients with HFpEF have shown a significant increase in LVEF at 6 months [ 35 ]. Moreover, esaxerenone prevented the deterioration of LVEF as well as worsening of fractional shortening and stroke volume in rats with salt-induced myocardial injury [ 33 ].…”

“…LAVI tended to decrease in this study, but not significantly; E/A and E/e′ also tended to decrease, with significant decreases in E/A in the total population and RASi subcohort and in E/e′ in the total population and CCB subcohort; no change in TRV was observed. Esaxerenone has been reported to significantly reduce E/e′ in hypertensive patients with HFpEF [ 35 ], and a meta-analysis of steroidal MRBs also found significant reductions in E/A, E/e′, and LAVI for patients with HFpEF [ 53 ]. Esaxerenone might contribute to the prevention of left ventricular systolic and diastolic dysfunction and transition to HFpEF in patients with LVH.…”