S-28-2: EFFECT OF ESAXERENONE ON NOCTURNAL BLOOD PRESSURE COMBINED WITH RENIN-ANGIOTENSIN SYSTEM INHIBITOR OR CALCIUM CHANNEL BLOCKER IN UNCONTROLLED HYPERTENSION

Abstract

Objective: To evaluate the nighttime blood pressure(BP)-lowering effects of esaxerenone with different concomitant antihypertensive treatments, we conducted a post hoc analysis of a multicenter, open-label, long-term phase 3 study (NCT02722265) of esaxerenone, a highly selective mineralocorticoid receptor blocker, alone or in combination with a calcium channel blocker (CCB) or a renin-angiotensin system (RAS) inhibitor in patients with essential hypertension. Design and method: Patients had previously untreated essential hypertension, or had received only one RAS inhibitor or CCB as a baseline antihypertensive agent at the start of the study. All patients had a sitting systolic BP of 140 to < 180 mmHg and a sitting diastolic BP of 90 to < 110 mmHg, a 24-h ambulatory BP of ≧130/80 mmHg. In this post hoc analysis, patients were classified into 3 treatment groups; esaxerenone monotherapy, combination with a CCB and combination with RAS inhibitor and targeted on the patient without any additional antihypertensive treatment at Week 28. For these 3 groups, mean changes in 24-hour, early morning, daytime, and nighttime systolic BP in 24-h ambulatory BP, mean changes in N-terminal pro B-type natriuretic peptide (NT-proBNP) levels, and changes in dipping pattern (extreme dippers, dippers, non-dippers, risers) were evaluated at 28 Week to include as many patients as possible available for analysis. Results: Of the total 368 patients in the study, 248 patients were included in this analysis and there were 153 in esaxerenone monotherapy, 48 in combination with a CCB and 48 in combination with a RAS inhibitor. Nighttime systolic BP statistically significantly decreased in all groups at Week 28 compared to baseline, with combination with a RAS inhibitor group showing the greatest change (-20.6 mmHg). Those changes were numerically greater than the daytime systolic blood pressure in all groups. The decrease in NT-proBNP from baseline to Week 28 was statistically significant in all group (p < 0.001, respectively) and the decrease in combination with RAS inhibitor was numerically greater than that of monotherapy. A statistically significant shift in dipping pattern and changes from riser/non-dipper to dipper/extreme dipper pattern were found at Week 28 in Monotherapy (p < 0.05) and the same trend of shifting was shown in combination with RAS inhibitor (p = 0.1615). The prevalence of riser/non-dipper pattern was decreased from 58.2% to 47.7% in monotherapy and from 54.2% to 39.6% in combination with RAS inhibitor. Conclusions: Esaxerenone would provide a useful treatment option for nocturnal hypertension, especially in combination with RAS inhibitor, in uncontrolled hypertension.