Efficacy and Safety of Spironolactone in Patients with Resistant Hypertension: A Meta-analysis of Randomised Controlled Trials

Background The treatment of resistant hypertension (RH) is challenging. Several observational studies have suggested that the addition of spironolactone to triple-drug therapy might have a promising anti-hypertensive effect on RH. To provide more definite evidence for the benefit of spironolactone, we performed a meta-analysis of randomised controlled trials (RCTs) to evaluate the efficacy and safety of spironolactone in RH patients. Methods Articles were searched from PubMed, EMBASE and Cochrane Library. Randomised controlled trials investigating the effect of additional spironolactone on office blood pressure (BP), ambulatory BP or adverse events in RH patients were included for analysis. Then quality assessment, subgroup, sensitivity, and publication bias analyses were performed. Results Five RCTs involving a total of 553 patients were eligible for inclusion. Compared with control therapies, additional spironolactone treatment in RH patients significantly decreased 24-h ambulatory systolic BP (ASBP, weight mean difference [WMD] = -10.50, 95% confidence interval [CI] = -12.30 to -8.71, P < 0.001), 24-h ambulatory diastolic BP (ADBP, WMD = -4.09, 95% CI = -5.28 to -2.91, P < 0.001), daytime ASBP (WMD = -10.20, 95% CI = -12.41 to -7.99, P < 0.001), daytime ADBP (WMD = -4.14, 95% CI = -5.50 to -2.78, P < 0.001), night-time ASBP (WMD = -10.02, 95% CI = -12.63 to -7.41), night-time ADBP (WMD = -3.21, 95% CI = -4.84 to -1.58, P < 0.001), office systolic BP (WMD = -16.99, 95% CI = -25.04 to -8.95, P < 0.001) and office diastolic BP (WMD = -6.18, 95% CI = -9.30 to -3.05, P < 0.001). However, serum potassium might be slightly elevated by additional spironolactone (WMD = 0.181, 95% CI = 0.042 to 0.319, P = 0.011). Conclusion Spironolactone combined with triple-drug therapy may be an effective and relatively safe strategy for the management of RH patients.