Sequential comparison of aldosterone synthase inhibition and mineralocorticoid blockade in patients with primary aldosteronism

Abstract

We compared the effects of aldosterone synthase inhibition with LCI699 with those of mineralocorticoid receptor blockade in patients with primary aldosteronism. After a 2-week placebo run-in, 14 patients with primary aldosteronism received oral LCI699 (0.5 mg b.i.d.) from day 1 to 14, LCI699 (1 mg b.i.d.) from day 15 to 29, and placebo from day 29 to 36. From day 36 to day 66, patients were treated with eplerenone (50 mg b.i.d., up-titrated to 100 mg b.i.d. in 12/14 patients), in addition to their previous antihypertensive treatment, which was maintained unchanged. Eplerenone significantly decreased more 24-h ambulatory SBP on day 66 than LCI699 on day 29 and the difference between the two treatment was -5.34 [95% confidence interval (CI) -10.30; -0.38)] mmHg (P = 0.027). Plasma potassium concentration achieved on eplerenone (4.30 ± 0.45 mmol/l) was significantly greater than on LCI699 (3.89 ± 0.35 mmol/l; P = 0.009). The increase in plasma renin concentration was significantly greater after eplerenone [+131% (range 61; 231)] than on LCI699 on day 29 [+39% (range 5; 86); P = 0.023]. LCI699 markedly decreased plasma aldosterone concentration by 75% (range -84;-63), whereas eplerenone markedly increased this concentration, from day 36, by 89% (range 40;154; P < 0.0001 vs. day 29). In patients with primary aldosteronism, the effects on blood pressure and plasma potassium and renin concentrations of 4 weeks of eplerenone treatment (50-100 mg b.i.d.) were more marked than those of 4 weeks of LCI699 treatment (0.5-1 mg b.i.d.). These two drugs had opposite effects on plasma aldosterone concentration.