PS-P15-8: EFFICACY AND SAFETY OF ESAXERENONE IN HYPERTENSIVE PATIENTS WITH TYPE 2 DIABETES AND RECEIVING SODIUM-GLUCOSE COTRANSPORTER 2 INHIBITORS (EAGLE-DH STUDY)
Authors: Motoki Hirohiko , Inobe Yoshito , Fukui Toshiki , Iwasaki Arata , Hiramitsu Shinya , Koyama Sekiya , Masuda Izuru , Sekimura Noriyuki , Yamamoto Kazuya , Sato Ai , Komatsu Mitsuhisa , Taguchi Takashi , Shiosakai Kazuhito , Sugimoto Kotaro , Kuwahara Koichiro 
Published: January 2023

Objective:
Hypertensive patients with type 2 diabetes mellitus (T2DM) who respond inadequately to antihypertensive therapy are at high risk for cardiorenal events and require effective treatment options. Clinical trials have shown that esaxerenone, a non-steroidal mineralocorticoid receptor blocker, has favorable antihypertensive and renoprotective effects in hypertensive patients with various characteristics including T2DM and albuminuria. However, clinical evidence is lacking regarding the concomitant use of esaxerenone and sodium-glucose cotransporter 2 (SGLT2) inhibitors in hypertensive patients with T2DM.
The study aimed to evaluate the efficacy and safety of esaxerenone and SGLT2 inhibitor combination therapy in Japanese hypertensive patients with T2DM who had an inadequate response to blood pressure (BP)-lowering treatment with renin angiotensin system (RAS) inhibitor or calcium channel blocker (CCB) monotherapy or combined therapy.

Design and method:
EAGLE-DH (jRCTs031200273) was a multicenter, open-label, interventional study in hypertensive patients (age, ≧ 20 years) with T2DM. Inclusion criteria were previous use of antihypertensive therapy (a RAS inhibitor, CCB, or RAS inhibitor plus CCB) and oral hypoglycemic drugs (a SGLT2 inhibitor with or without one or two other oral hypoglycemic drugs) for ≧ 12 weeks; morning home systolic BP (SBP) 125 to < 160 mmHg and/or diastolic BP (DBP) 75 to < 100 mmHg; and eGFRcreat ≧ 30 mL/min/1.73m2 at baseline. Over the 24-week study period, esaxerenone dose was started at 1.25 or 2.5 mg/day, and based on the individual patient's condition, the dose could be titrated at weeks 4 and 8 to a maximum of 5 mg/day. The primary endpoints were change in morning home BP from baseline to weeks 12 and 24. Secondary endpoints included change in bedtime home BP and office BP, proportion of patients achieving target SBP/DBP (home, < 125/75 mmHg; office, < 130/80 mmHg), change in urine albumin-to-creatinine ratio (UACR), and safety variables including adverse events, eGFR, and serum potassium.

Results:
The study population comprised 93 patients. Baseline characteristics were mean age, 66.3 years; male, 68.8%; mean morning home SBP/DBP, 136.4/82.3 mmHg; mean UACR 145.3 mg/g creatinine; one RAS inhibitor use, 33.3%; one CCB inhibitor use, 19.4%; RAS inhibitor plus CCB, 47.3%; mean HbA1c 6.8%; mean serum potassium, 4.2 mEq/L; and mean eGFRcreat 66.8 mL/min/1.73m2. Efficacy and safety results will be presented at the conference.

Conclusions:
EAGLE-DH will provide the first evidence from clinical practice for the efficacy of esaxerenone plus SGLT2 inhibitor in reducing morning/bedtime home and office BP with improving albuminuria as well as for its safety profile in Japanese hypertensive patients with T2DM.