Factors Associated with the Antihypertensive Effect of Esaxerenone and Serum Potassium Elevation: A Pooled Analysis of Seven PhaseIII Studies.

Abstract

This study investigated factors associated with the antihypertensive effects of esaxerenone and theincidence of serum potassium elevation in patients with hypertension. Using pooled data from seven phaseIII studies, the study analyzed factors associated with changes in office systolic (SBP) and diastolic (DBP) blood pressure from baseline to 12weeks, and factors associated with incidence of serum potassium levels ≥ 5.5mEq/L in esaxerenone-treated patients. Overall, 1466 and 1472 patients were included in the fullanalysis and safety analysis sets, respectively. Male sex (4.02/2.40mmHg), weight ≥ 78.4kg (4.62/2.09mmHg), hypertension duration ≥ 10years (2.66/1.71mmHg), prior antihypertensive treatment (2.38/1.40mmHg), plasma aldosterone concentration ≥ 120pg/mL (1.66/1.17mmHg), urinary albumin-to-creatinine ratio (UACR) ≥ 300mg/gCr (8.94/4.85mmHg) or 30-299mg/gCr (5.17/4.15mmHg), and smoking (2.62/1.27mmHg)were associated with mean changes in SBP andDBP. Fasting blood glucose ≥ 126mg/dL (- 2.73mmHg) was associated with the mean change in SBP only, and older age (65-74years, - 2.12mmHg; and ≥ 75years, - 3.06mmHg) with mean change in DBP only. Factors significantly associated with incidence of serum potassium levels ≥ 5.5mEq/L were higher baseline serum potassium (≥ 4.5mEq/L, odds ratio [OR] 6.702); lower estimated glomerular filtration rate (≥ 90mL/min/1.73m2, OR 0.148; 60-89mL/min/1.73m2, OR 0.331 vs 30-59mL/min/1.73m2, respectively); higher UACR (30-299mg/gCr, OR 7.317); higher DBP (≥ 100mmHg, OR 3.248); and gradeI hypertension (OR 2.168). Esaxerenone is effective in patients with a broad range of backgrounds, though some factors may predict increased benefit. Regarding elevated serum potassium, careful therapeutic management is recommended for patients with higher baseline serum potassium and reduced renal function. UMIN000047026.