OR-53: Efficacy and safety of eplerenone, enalapril, and eplerenone/enalapril combination therapy in patients with left ventricular hypertrophy

Hypertension and up-regulation of the renin-angiotensin-aldosterone system (RAAS) have been linked to left ventricular hypertrophy (LVH) and cardiac fibrosis. Agents that block the production or action of aldosterone or angiotensin II lower BP, regress LVH, and reduce cardiac fibrosis. This 9-month, double-blind, randomized, forced-titration study compared the efficacy and tolerability of eplerenone (EPL), a selective aldosterone blocker, with enalapril (ENAL), an ACE inhibitor, and EPL+ENAL combination therapy for BP reduction and LV-mass regression. Patients with mild-to-moderate hypertension (DBP ≥90 mmHg and 140 mmHg and ≤200 mmHg) and LVH 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, if BP remained uncontrolled with the full daily dose (DBP ≥90 mmHg or SBP >180 mmHg), HCTZ 12.5 mg, HCTZ 25 mg, or amlodipine 10 mg were added. The change from baseline in left ventricular mass (LVM) as assessed by MRI was the primary endpoint. BP control, change in microalbuminuria (UACR), and treatment safety and tolerability were assessed at the 9-month end point. Mean baseline and mean change from baseline for MRI LVM, BP, and UACR: A significantly greater proportion of ENAL patients experienced coughing than EPL patients (14.1% vs 3.1%, (P =0.033). In conclusion, eplerenone monotherapy was as effective as enalapril monotherapy in regressing LVH. The combination of eplerenone and enalapril caused significantly greater reduction in LVM than eplerenone alone. All treatments significantly reduced microalbuminuria. These data suggest that eplerenone treatment confers cardiovascular benefit and that this benefit is additive with an ACE inhibitor (see Figure).