A double-blind, randomized study comparing the antihypertensive effect of eplerenone and spironolactone in patients with hypertension and evidence of primary aldosteronism

Abstract

Background: Eplerenone is claimed to be a more selective blocker of the mineralocorticoid receptor than spironolactone being associated with fewer antiandrogenic side-effects. We compared the efficacy, safety and tolerability of eplerenone versus spironolactone in patients with hypertension associated with primary aldosteronism.

Methods: The study was multicentre, randomized, double-blind, active-controlled, and parallel group design. Following a single-blind, placebo run-in period, patients were randomized 1: 1 to a 16-week double-blind, treatment period of spironolactone (75-225 mg once daily) or eplerenone (100-300 mg once daily) using a titration-to-effect design. To be randomized, patients had to meet biochemical criteria for primary aldosteronism and have a seated DBP at least 90 mmHg and less than 120 mmHg and SBP less than 200 mmHg. The primary efficacy endpoint was the antihypertensive effect of eplerenone versus spironolactone to establish noninferiority of eplerenone in the mean change from baseline in seated DBP.

Results: Changes from baseline in DBP were less on eplerenone (-5.6 ± 1.3 SE mmHg) than spironolactone (-12.5 ± 1.3 SE mmHg) [difference, -6.9 mmHg (-10.6, -3.3); P<0.001]. Although there were no significant differences between eplerenone and spironolactone in the overall incidence of adverse events, more patients randomized to spironolactone developed male gynaecomastia (21.2 versus 4.5%; P=0.033) and female mastodynia (21.1 versus 0.0%; P=0.026).

Conclusion: The antihypertensive effect of spironolactone was significantly greater than that of eplerenone in hypertension associated with primary aldosteronism.