Efficacy and Safety of Esaxerenone in Hypertensive Patients with Diabetes Mellitus Undergoing Treatment with Sodium-Glucose Cotransporter 2 Inhibitors (EAGLE-DH)

Abstract

Introduction The EAGLE-DH study assessed the efficacy and safety of esaxerenone in hypertensive patients with diabetes mellitus receiving sodium-glucose cotransporter 2 (SGLT2) inhibitors. Methods In this multicenter, open-label, prospective, interventional study, esaxerenone was started at 1.25 or 2.5 mg/day and could be gradually increased to 5 mg/day on the basis of blood pressure (BP) and serum potassium levels. Oral hypoglycemic or antihypertensive medications prior to obtaining consent was continued. Data were evaluated in the total population and creatinine-based estimated glomerular filtration rate (eGFR) subcohorts (eGFR ≥ 60 mL/min/1.73 m 2 [G1–G2 subcohort] and 30 to < 60 mL/min/1.73 m 2 [G3 subcohort]). Results In total, 93 patients were evaluated (G1–G2, n = 49; G3, n = 44). Morning home systolic/diastolic BP values (SBP/DBP) were significantly reduced from baseline to week 12 (− 11.8 ± 10.8/− 5.1 ± 6.3 mmHg, both P < 0.001) and week 24 (− 12.9 ± 10.5/− 5.7 ± 6.3 mmHg, both P < 0.001). Similar results were observed in both eGFR subcohorts. The urinary albumin-to-creatinine ratio significantly decreased from baseline to week 24 in the total population (geometric percentage change, − 49.1%, P < 0.001) and in both eGFR subcohorts. The incidences of treatment-emergent adverse events (TEAEs) and drug-related TEAEs were 45.2% and 12.9%, respectively; most were mild or moderate. Serum potassium levels increased over the first 2 weeks of esaxerenone treatment, gradually decreased by week 12, and remained constant to week 24. One patient in the G1–G2 subcohort had serum potassium levels ≥ 5.5 mEq/L. No patients had serum potassium ≥ 6.0 mEq/L. Conclusion Esaxerenone effectively lowered BP, was safe, and showed renoprotective effects in hypertensive patients with diabetes mellitus receiving treatment with SGLT2 inhibitors. Esaxerenone and SGLT2 inhibitors did not interfere with either drug’s efficacy and may reduce the frequency of serum potassium elevations, suggesting they are a compatible combination. Clinical Trial Registration jRCTs031200273. Supplementary Information The online version contains supplementary material available at 10.1007/s12325-023-02633-8.

Antihypertensive effect of esaxerenone and correlation between brachial and wrist home monitoring devices in patients with nocturnal hypertension: A post hoc analysis of the EARLY‐NH study

“… 15 Similar antihypertensive effects were observed in previous postlaunch studies involving different patient populations such as those with diabetic kidney disease (EX‐DKD), diabetes mellitus receiving sodium‐glucose co‐transporter‐2 inhibitors (EAGLE‐DH), and essential hypertension (ENaK). 25 , 26 , 27 This post hoc analysis revealed that, regardless of the device used, treatment with esaxerenone for 12 weeks resulted in good nighttime home SBP control (< 120 mmHg) in many patients who achieved target morning home SBP (< 135 mmHg). Considering the strong relationship between nocturnal hypertension and cardiovascular disease risk, the clinical implications of our findings, in particular the ability of esaxerenone to control nighttime home SBP, are encouraging.…”