Renal function and hyperkalemia with first-line eplerenone in obese patients with hypertension: randomized safety data from the HEBRO trial

Background Mineralocorticoid receptor antagonists (MRAs) are effective antihypertensive agents; however, their use as first-line therapy remains limited due to concerns regarding hyperkalemia and renal impairment. Purpose To compare renal function changes and hyperkalemia incidence between eplerenone- and irbesartan-based first-line treatment strategies in obese patients with essential hypertension. Methods HEBRO (antiHypertensive treatment with Eplerenone vs. iBesartan in hypeRtensive Obese patients) is a prospective, randomized, open-label, multicenter trial enrolling 198 hypertensive patients aged 30–75 years with obesity (BMI ≥30 kg/m²) and hypertension confirmed by both office and ambulatory blood pressure (ABPM) measurements. Patients underwent stratified randomization (according to age, sex, baseline office BP, and eGFR) to eplerenone 25 mg twice daily (n=99) or irbesartan 150 mg once daily (n=99). At 2 and 4 months, stepwise up-titration with amlodipine 5 mg and indapamide 1.5 mg, respectively, was performed if mean ABPM remained >130/80 mmHg. Renal function (eGFR, serum creatinine) and potassium were assessed at baseline and 6 months. Between-group differences in change from baseline were analyzed using appropriate independent-samples tests. Hyperkalemia was defined as serum potassium ≥5.5 mmol/L. Results Baseline characteristics were balanced between groups: 50.5% men, age 55.5 ± 10.1 years, BMI 34.2 ± 3.5 kg/m², mean eGFR 85.7 ± 16.1 mL/min/1.73m², and diabetes prevalence 13.6%. A total of 162 patients were included in this safety analysis. Mean change in serum potassium was 0.02 ± 0.45 mmol/L in the eplerenone arm and 0.01 ± 0.45 mmol/L in the irbesartan arm (p=0.86). Hyperkalemia (≥5.5 mmol/L) was rare and occurred in 1.2% and 1.3% of patients, respectively (p=1.00), with no treatment discontinuations. Median change in serum creatinine was 0.00 mg/dL in both groups (p=0.70). Similarly, median change in eGFR was 0.0 mL/min/1.73m² in both groups (p=0.71). Conclusion In obese hypertensive patients, first-line treatment with eplerenone was not associated with excess renal function decline or clinically significant hyperkalemia compared with irbesartan. These findings support the renal safety of MRA-based first-line therapy in this population.