Antiproteinuric efficacy of eplerenone, enalapril, and eplerenone/enalapril combination therapy in diabetic hypertensives with microalbuminuria

Hypertensive patients with diabetes have increased likelihood of proteinuria, a predictor of end-stage renal disease. This 24-week, double-blind study compared the renal and antihypertensive effects and the tolerability of eplerenone (EPL), a selective aldosterone blocker, enalapril (ENAL), an ACE inhibitor, and EPL+ENAL combination therapy in hypertensive patients with diabetes and proteinuria. Diabetic type 2 patients with mild-to-moderate hypertension (DBP ≥95 mmHg and <110mmHg; SBP <180 mmHg) and microalbuminuria (UACR ≥50 mg/g) were randomly assigned to receive EPL 200 mg QD, ENAL 40 mg QD, or EPL 200 mg/ENAL 10 mg (doses were reached by forced titration over 4 weeks). At Week 8 or later, if BP remained uncontrolled (DBP ≥90 mmHg), HCTZ 12.5 mg was added and further up-titrated to 25 mg if necessary. UACR, BP, and safety were assessed at Weeks 8 and 24. Geometric mean reductions in UACR and adjusted mean changes in SBP/DBP: Addition of HCTZ was required by 36/84 EPL patients, 43/81 ENAL patients, and 25/79 EPL+ENAL patients. Elevated K+ (≥6.0 mEq/L) was observed in 8 EPL, 2 ENAL, and 8 EPL+ENAL subjects. More patients were withdrawn for hyperkalemia in the EPL+ENAL group (14) than in the EPL (6) and ENAL (2) groups. Other AEs were similar among treatment groups.