Spironolactone versus Eplerenone in Patients with Resistant Hypertension: A Systematic Review and Indirect Meta-analysis

Background: Spironolactone and eplerenone, both mineralocorticoid receptor antagonists (MRAs), have been shown to be effective in the management of resistant hypertension (RH), although there is a lack of randomised controlled trials (RCTs) that directly comparing the two. This systematic review and indirect meta-analysis compares the two MRAs and their effectiveness in lowering blood pressure (BP) in patients with RH. Methods: RCTs comparing eplerenone or spironolactone with a placebo in RH patients were included in the review. The primary outcome was the mean difference (MD) of systolic blood pressure (SBP) and diastolic blood pressure (DBP). The secondary outcome was the MD of serum potassium levels. The pooled estimates of mean BP and mean potassium level difference were then analysed to attain the adjusted indirect comparisons. Results: Six RCTs involving 665 patients were included in the systematic review. The pooled MD of systolic and diastolic BP between eplerenone and placebo showed a reduction of −0.38 (p=0.0007) and −4.45 (p<0.0001), respectively. The pooled MD of systolic and diastolic BP between spironolactone and placebo showed a reduction of −4.82 (p=0.01) and −2.31 (p=0.006), respectively. The pooled MD of serum potassium levels between eplerenone and placebo as well as spironolactone and placebo was 0.16 (p=0.39) and −0.08 (p=0.59), respectively. An indirect comparison meta-analyses of the MD in systolic and diastolic BP (systolic MD 1.66; 95% CI [−3.46–6.78]; p=0.5250 and diastolic MD 2.14; 95% Cl [−0.63–4.91]; p=0.1293) as well as mean serum potassium levels (MD 0.24; 95% Cl, [−0.23–0.71]; p=0.313) between spironolactone and eplerenone, showed no significant difference. Conclusion: Spironolactone and eplerenone showed an equal reduction in systolic and diastolic BP, as well as serum potassium levels in patients with RH.