OR-55: Comparison of eplerenone and losartan in patients with low-renin hypertension

Hypertensive patients with low plasma renin may be salt/volume-sensitive and should therefore respond better to aldosterone blockade than ACE inhibitors or ARBs. To test this hypothesis, this 16-week, randomized, double-blind study in low-renin hypertensives compared the efficacy and safety of eplerenone (EPL), a selective aldosterone blocker, and losartan (LOS), an ARB. Patients with low-renin hypertension (morning Plasma Renin Activity ≤1.0 ng/mL/h or an Active Renin value ≤25 pg/mL) were randomized to receive initially either EPL 100 mg QD (n=86) or LOS 50 mg QD (n=82). At Week 4, if BP was uncontrolled (DBP ≥90 mmHg), study medications were up-titrated to EPL 200 mg QD or LOS 100 mg QD. At Week 8, if BP remained uncontrolled, HCTZ 12.5 mg was added and, if necessary, up-titrated to 25 mg at Week 12. At Weeks 8 and 16, BP, RAAS hormone profile, and safety were assessed. Mean Active Renin levels at baseline were 11.7 mU/L and 12.7 mU/L in the EPL and LOS groups, respectively. At the end of the monotherapy part of the trial (Week 8), mean changes from baseline in SBP/DBP were significantly greater in the EPL group than in the LOS group (EPL -15.8/-9.3 mmHg, LOS -10.1/-6.7 mmHg, P=0.017/0.050). At Week 16, after the allowed addition of HCTZ, the mean changes from baseline in SBP/DBP were similar in the EPL group (-18.3/-10.8 mmHg) and the LOS group (-15.0/-9.8 mmHg), but the cumulative percentage of patients requiring HCTZ add-on therapy was less in the EPL group (32.5%) than in the LOS group (55.6%). Increases in Active Renin levels were similar in the two groups at Week 8 (EPL +50.1%, LOS +63.8%, P=0.416) and Week 16 (EPL +73.0%, LOS +83.3%, P=0.635). Increases in serum aldosterone levels were greater in the EPL group at Week 8 (EPL +74.7%, LOS -18.7%; P