Among patients with uncontrolled nocturnal hypertension who are receiving an angiotensin receptor blocker (ARB) or calcium-channel blocker (CCB), esaxerenone is associated with a 24-hour sustained antihypertensive effect beyond nocturnal hypertension, according to a study in Hypertension Research.
The EARLY-NH study evaluated the nighttime home BP-lowering effect of esaxerenone in patients with uncontrolled nocturnal hypertension being treated with an ARB or CCB. The open-label, prospective, interventional study was conducted at 17 centers in Japan from April 2021 to March 2022.
The study included a 4-week observation period and a 12-week treatment period, with esaxerenone administered orally once daily. Participants were aged 20 years or older, received a constant dose of 1 ARB or 1 CCB for 4 weeks before initiation of esaxerenone, and had a nighttime systolic BP (SBP) of 120 mm Hg or higher measured with a brachial device.
Home BP was measured with use of a brachial (OMRON HEM-9700T) or wrist (OMRON HEM-9601T) home BP monitoring (HBPM) device. The primary endpoint was change in nighttime home SBP and diastolic BP (DBP) measured via the brachial device from baseline to end of treatment (EOT).
A total of 93 patients were included in the full analysis, 101 were included in the safety analysis, and 89 were included in the per-protocol set. The study was completed by 82 patients. Overall, participants had a mean age of 67.6 years and 50.5% were men.
A statistically significant decrease in nighttime home BP levels from baseline to EOT according to the brachial device occurred in the overall population (-12.9/-5.4 mm Hg, P <.001) and the CCB and ARB subcohorts (-10.0/-4.4 mm Hg and -16.2/-6.6 mm Hg, respectively; each P <.001). Nighttime home BP measured via the wrist device also demonstrated a significant decrease in the total population and ARB and CCB subcohorts. Comparable significant changes occurred in morning home BP, bedtime home BP, and office BP in the total population and ARB and CCB subcohorts.
The overall proportion of patients who met target BP levels at week 12 in the full analysis was 17.2% for nighttime home BP (brachial), 30.1% for nighttime home BP (wrist), 9.7% for morning home BP, and 25.8% for bedtime home and office BP, with similar results occurring in the ARB and CCB subcohorts.
Urinary albumin-to-creatinine ratio was significantly reduced in the total population (geometric percentage change from baseline to week 12, -26.2%; P <.001). N-terminal pro-brain natriuretic peptide levels decreased significantly in the overall and CCB subcohort (geometric percentage change from baseline to week 12, -18.5% and -18.6%, respectively; both P <.01).
Treatment-emergent adverse events (TEAEs) were reported in 39 patients, 3 of whom discontinued treatment. Serious TEAEs occurred in 1 patient (acute pyelonephritis), which was not related to esaxerenone treatment. Drug-related TEAEs occurred in 17 patients, of whom 3 discontinued treatment.
Limitations of the study include the small sample size, which may have led to insufficient statistical power. In addition, the study has a single-arm design that does not include a placebo, and generalizability of the results to other populations should be interpreted with caution.
“Esaxerenone may not only be an optimal treatment option for patients with nocturnal hypertension, but may also be useful in the total BP management,” wrote the investigators.
Disclosure: The EARLY-NH study was supported by Daiichi Sankyo Co, Ltd. Some of the study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.
Kario K, Nishizawa M, Kato M, et al. Nighttime home blood pressure lowering effect of esaxerenone in patients with uncontrolled nocturnal hypertension: the EARLY-NH study. Hypertens Res. Published online May 12, 2023. doi: 10.1038/s41440-023-01292-0