Esaxerenone produces favourable night-time BP-lowering effect in Asians

The novel highly selective mineralocorticoid receptor blocker esaxerenone holds promise in the treatment of nocturnal hypertension, yielding substantial reductions in night-time blood pressure (BP), especially in Japanese patients with a riser pattern, as well as in N-terminal pro B-type natriuretic peptide (NT-proBNP) levels, according to a post hoc analysis of a phase III study.

Moreover, the drug induces a positive change in dipping patterns.

The analysis included 368 esaxerenone-treated patients (mean age 56.2 years, 77.7 percent men) with essential hypertension, of whom 53 (14.4 percent), 162 (44.0 percent), 123 (33.4 percent), and 29 (7.9 percent) were categorized as risers, nondippers, dippers, and extreme dippers, respectively.

Night-time systolic BP decreased in all dipping pattern groups at week 28; the change was greatest in the riser group (−25.5 mm Hg) and the least in extreme dipper group (−4.3 mm Hg). More importantly, dipping patterns shifted during this period: some patients with a riser or nondipper pattern at baseline showed a dipper or extreme dipper pattern at week 28 (p<0.0001). The prevalence of the riser pattern dropped from 14.4 percent to 9.8 percent, while that that of the nondipper pattern decreased from 44.7 percent to 39.2 percent. [Hypertens Res 2022;45:97-105]

Another notable improvement seen was the biomarker of cardiovascular disease NT-proBNP. Its concentration significantly decreased from baseline at week 28 in patients across all dipping pattern groups (p<0.001 for all). At baseline, the number of patients with NT-proBNP <55 pg/mL was lowest among risers versus the other dipping pattern types, but this difference disappeared at week 28.

“The main causes of nocturnal hypertension include advanced structural vascular disease, increased salt sensitivity, and a diet high in salt, particularly in patients with increasing basal night-time BP,” the investigators pointed out. [Hypertension 2018;71:997-1009]

Therefore, the strong mineralocorticoid receptor inhibitory action of esaxerenone potentially explains the decrease in nocturnal BP, which in turn lowers the CVD risk, they added.

“This effect on nocturnal BP is of particular relevance in Asian patients, given their higher prevalence of hypertension-related stroke and heart failure compared with non-Asian patients,” the investigators said. [Hypertension 2018;71:375-382; J Clin Hypertens 2019;21:1250-1283]

In the study, all patients had been given esaxerenone, with a starting dose of 2.5 mg/day then uptitrated to 5 mg/day if required, as a monotherapy or in combination with a calcium channel blocker or a renin–angiotensin system inhibitor (n=123, 33.4 percent). After the first 12 weeks of treatment, an additional antihypertensive agent could be added if required to achieve the target BP; the total treatment period was 28 or 52 weeks.

“As far as we know, there are no previous reports on antihypertensive agents that change the dipping pattern distribution,” according to the investigators.

“Considering the high risk of organ damage to the brain and heart and cardiovascular mortality associated with nondipper and riser patterns, antihypertensive agents with BP-lowering effects in patients with these dipping patterns would be of great value. Our results suggest that esaxerenone may be a suitable treatment option for patients with riser and nondipper patterns,” they added.

Despite the encouraging results, the investigators acknowledged the presence of some limitations. First, there was no prespecified data plan due to the study being a post hoc analysis. Also, there was no comparator agent, and only comparisons with the baseline values were determined. Finally, the sample size for risers and extreme dippers was very small, and generalizability to other ethnic populations may be limited.