BLOOD PRESSURE LOWERING EFFECTS AND SAFETY OF ESEXERENONE, NEWLY AVAILABLE MINERALOCORTICOID RECEPTOR BLOCKER

Abstract

Objective: Esaxerenone (CS-3150) is a novel, highly potent, selective and long acting non-steroidal mineralocorticoid receptor (MR) blocker with MR blocking action of IC50 3.7 nM, other steroid hormone receptors blocking action of IC50 >5000 nM and half life loss of 18.6 hours. The authors aimed to investigate blood pressure (BP)-lowering ability and safety of esaxerenone in resistant hypertensive patients by add-on or by replacement from spironolactone or eplerenone. Design and method: This study was designed as a prospective observational study in 230 patients, approved by the local ethical committee and followed for 12 weeks. In add-on group, 52 resistant hypertensive patients, whose office BP was > 130/80 (<75 years old) or 140/90 (>75 years old) treated with at least three hypertensive agents (CCBs, RAS inhibitors and diuretics) according to the Japanese Society of Hypertension Guidelines for the Management of Hypertension (JSH 2019), were treated by the add-on use of esaxerenone. In replacement group, 208 resistant hypertensive patients, whose BP was controlled by at least 4 antihypertensive drugs including spironolactone or eplerenone, were medicated with esaxerenone by replacement from spironolactone or eplerenone. Results: In add-on group, both systolic and diastolic BP were significantly lowered from 139 ± 16 / 82 ± 14 mmHg (means ± SD) to 129 ± 16 / 79 ± 12 mmHg (p < 0.0001 and p = 0.0185, respectively) with mean esaxerenone dose of 1.44 mg. In replacement group, systolic BP was significantly lowered from 126 ± 16 mmHg (means ± SD) to 120 ± 14 mmHg (p < 0.0001), but diastolic BP was not, with mean esaxerenone dose of 1.58 mg once a day, which was changed from mean spironolactone and eplerenone doses of 34 and 58 mg, respectively. In add-on group, serum potassium concentration was significantly increased from 4.18 ± 0.46 to 4.40 ± 0.58 mmol/L and eGFR was decreased from 74.2 ± 23.9 to 66.9 ± 24.0, but those in replacement group were not significantly changed. Conclusions: This study suggested that esaxerenone has more potent BP lowering ability than spironolactone or eplerenone especially in systolic BP and has the equivalent safety.