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How effective is spironolactone for treating resistant hypertension?

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A very effective. Spironolactone reduces systolic blood pressure (SBP) by 11 to 17 mm Hg and diastolic blood pressure (DBP) by up to 6 mm Hg in patients with resistant hypertension taking 3 or more medications (strength of recommendation [SOR]: C, meta-analysis of randomized controlled trials [RCTs] of disease-oriented evidence).




A 2017 meta-analysis of 4 RCTs (869 patients) evaluated the effectiveness of prescribing spironolactone for patients with resistant hypertension, defined as above-goal blood pressure (BP) despite treatment with at least 3 BP-lowering drugs (at least 1 of which was a diuretic).1 All 4 trials compared spironolactone 25 to 50 mg/d with placebo. Follow-up periods ranged from 8 to 16 weeks. The primary outcomes were systolic and diastolic BPs, which were evaluated in the office, at home, or with an ambulatory monitor.

Spironolactone markedly lowers systolic and diastolic BP

A statistically significant reduction in SBP occurred in the spironolactone group compared with the placebo group (weighted mean difference [WMD] = −16.7 mm Hg; 95% confidence interval [CI], −27.5 to −5.8 mm Hg). DBP also decreased (WMD = −6.11 mm Hg; 95% CI, −9.34 to −2.88 mm Hg).

Because significant heterogeneity was found in the initial pooled results (I2 = 96% for SBP; I2 = 85% for DBP), investigators performed an analysis that excluded a single study with a small sample size. The re-analysis continued to show significant reductions in SBP and DBP for spironolactone compared with placebo (SBP: WMD = −10.8 mm Hg; 95% CI, −13.16 to −8.43 mm Hg; DBP: WMD = −4.62 mm Hg; 95% CI, −6.05 to −3.2 mm Hg; I2 = 35%), confirming that the excluded trial was the source of heterogeneity in the initial analysis and that spironolactone continued to significantly lower BP for the treatment group compared with controls.

Add-on treatment with spironolactone also reduces BP

A 2016 meta-analysis of 5 RCTs with a total of 553 patients examined the effectiveness of add-on treatment with spironolactone (25-50 mg/d) for patients with resistant hypertension, defined as failure to achieve BP < 140/90 mm Hg despite treatment with 3 or more BP-lowering drugs, including one diuretic.2 Spironolactone was compared with placebo in 4 trials and with ramipril in the remaining study. The follow-up periods were 8 to 16 weeks. Researchers separated BP outcomes into 24-hour ambulatory systolic/diastolic BPs and office systolic/diastolic BPs.

The 24-hour ambulatory BPs were significantly lower in the spironolactone group compared with the control group (24-hour SBP: WMD = −10.5 mm Hg; 95% CI, −12.3 to −8.71 mm Hg; 24-hour DBP: WMD = −4.09 mm Hg; 95% CI, −5.28 to −2.91 mm Hg). No significant heterogeneity was noted in these analyses.

Office-based BPs also were markedly reduced in spironolactone groups compared with controls (office SBP: WMD = −17 mm Hg; 95% CI, −25 to −8.95 mm Hg); office DBP: WMD = −6.18 mm Hg; 95% CI, −9.3 to −3.05 mm Hg). Because the office-based BP data showed significant heterogeneity (I2 = 94% for SBP and 84.2% for DBP), 2 studies determined to be of lower quality caused by lack of detailed methodology were excluded from analysis, yielding continued statistically significant reductions in SBP (WMD = −11.7 mm Hg; 95% CI, −14.4 to −8.95 mm Hg) and DBP (WMD = −4.07 mm Hg; 95% CI, −5.6 to −2.54 mm Hg) compared with controls. Heterogeneity also decreased when the 2 studies were excluded (I2 = 21% for SBP and I2 = 59% for DBP).

How spironolactone compares with alternative drugs

A 2017 meta-analysis of 5 RCTs with 662 patients evaluated the effectiveness of spironolactone (25-50 mg/d) on resistant hypertension in patients taking 3 medications compared with a control group—placebo in 3 trials, placebo or bisoprolol (5-10 mg) in 1 trial, and an alternative treatment (candesartan 8 mg, atenolol 100 mg, or alpha methyldopa 750 mg) in 1 trial.3 Follow-up periods ranged from 4 to 16 weeks. Researchers evaluated changes in office and 24-hour ambulatory or home BP and completed separate analyses of pooled data for spironolactone compared with placebo groups, and spironolactone compared with alternative treatment groups.

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