Efficacy and safety of eplerenone in the management of mild to moderate arterial hypertension: systematic review and meta-analysis

Abstract

Background: The role of eplerenone in arterial hypertension has been investigated only in small studies. To systematically assess the efficacy and tolerability of eplerenone in patients with mild to moderate arterial hypertension, we did a meta-analysis of controlled randomized trials.

Methods: We performed an electronic literature search of Medline, Pubmed, Scopus and Cochrane databases for studies published up to March 31, 2014. Randomized studies comparing eplerenone with placebo or other antihypertensive drugs for net reduction of systolic and diastolic blood pressures (SBP; DBP) from baseline and for incidence of adverse events were considered. Weighted mean differences (WMD) and odds ratios with 95% confidence interval were calculated for continuous and dichotomous data, respectively.

Results: A total of 11 trials and 3566 patients were overall included. Compared to placebo, eplerenone significantly reduced either SBP [WMD -8.07, 95% CI -8.17 to -7.96 mm Hg, p < 0.00001] and DBP [WMD -4.08, -4.15 to -4.01 mm Hg, p < 0.00001]. In the overall comparison, reduction of both SBP and DBP with eplerenone was greater than other antihypertensive agents (WMD for SBP -1.50 mm Hg, p < 0.0001; WMD for DBP -0.54 mm Hg, p < 0.00001); this was essentially driven by a greater anti-hypertensive action vs enalapril and losartan for SBP and vs losartan for DBP. Rates of any adverse event were significantly higher with eplerenone than placebo (odds ratio 1.37, 95% CI 1.1 to 1.71; p = 0.005), whereas the occurrence of serious adverse events and hyperkalemia was similar. There was no difference between eplerenone and other antihypertensives in the frequency of any or serious adverse events, whereas hyperkalemia was more common with eplerenone (odds ratio 2.36, 95% CI 1.00 to 5.57; p = 0.05).

Conclusion: This study-level meta-analysis provides a robust evidence that eplerenone has a reassuring safety profile and is effective in lowering blood pressure in patients with mild-to-moderate hypertension; this effect is at least comparable to that of other anti-hypertensive agents (PROSPERO Registration No. CRD42014010071).

Keywords: Aldosterone; Arterial hypertension; Blood pressure; Eplerenone; Mineralocorticoid receptor antagonist.