Is Aldactone (Spironolactone) Used for Hypertension?
Yes, spironolactone (Aldactone) is FDA-approved and guideline-recommended for treating hypertension, particularly as add-on therapy when blood pressure remains uncontrolled on other agents, and it is the most effective fourth-line agent for resistant hypertension. 1, 2, 3
Primary Indication for Hypertension
Spironolactone is specifically indicated as add-on therapy to lower blood pressure in patients not adequately controlled on other agents, with the goal of reducing fatal and nonfatal cardiovascular events, primarily strokes and myocardial infarctions. 1 The FDA label explicitly states this indication, and multiple guidelines reinforce this role. 2, 1
Role in Resistant Hypertension
Spironolactone is the preferred fourth-line agent when blood pressure remains ≥140/90 mmHg (or ≥130/80 mmHg per newer guidelines) despite optimal doses of three antihypertensive medications including a diuretic. 3, 2 The American Heart Association and American College of Cardiology both recommend adding low-dose spironolactone (25-50 mg daily) in this setting, provided serum potassium is <4.5 mmol/L and eGFR is >45 mL/min/1.73m². 3, 2
Evidence of Effectiveness
Spironolactone provides significant additional blood pressure reduction when added to multidrug regimens in resistant hypertension, with observational studies and randomized trials demonstrating its superiority. 2
The ASPIRANT trial showed spironolactone 25 mg reduced daytime ambulatory systolic BP by 5.4 mm Hg compared to placebo (P=0.024), with even greater reductions in nighttime systolic BP (-8.6 mm Hg, P=0.011) and office systolic BP (-6.5 mm Hg, P=0.011). 4
Prospective studies demonstrate average blood pressure reductions of 22/10 mm Hg when spironolactone is added to resistant hypertension regimens. 5
An observational study of 119 patients showed mean reductions of 21.7/8.5 mm Hg (P<0.001) with median dose of 25 mg spironolactone. 6
Spironolactone is clearly established as the most effective fourth agent for treatment of uncontrolled resistant hypertension, even in patients without demonstrable hyperaldosteronism. 7
Dosing Strategy
Start with 25 mg once daily, which can be increased to 50 mg daily if blood pressure remains uncontrolled and the medication is well-tolerated. 3, 2
The mean daily dose in major trials was 26 mg, and doses greater than 100 mg/day generally do not provide additional blood pressure reductions. 1
Doses of 25-50 mg/day are effective and minimize adverse effects like gynecomastia, which are less likely at these lower doses. 2
Monitoring Requirements
Check serum potassium and creatinine 5-7 days after initiation, then every 3-6 months thereafter. 3
Discontinue if potassium rises above 5.5-6.0 mmol/L. 3
Hyperkalemia occurs in approximately 4% of patients, with increased risk when combined with ACE inhibitors or ARBs. 3
Prerequisites Before Adding Spironolactone
Before adding spironolactone as a fourth agent, ensure:
The patient is on maximally tolerated doses of three medications: a long-acting calcium channel blocker, a renin-angiotensin system blocker (ACE inhibitor or ARB), and an appropriate diuretic. 3
Switch from hydrochlorothiazide to chlorthalidone or indapamide for superior 24-hour blood pressure control. 3, 2
Use loop diuretics instead of thiazides if eGFR <30 mL/min/1.73m² or clinical volume overload is present, as thiazides become ineffective at lower GFR. 3
Rule out pseudoresistance by confirming proper blood pressure measurement technique, excluding white coat hypertension with ambulatory monitoring, and verifying medication adherence. 2, 3
Critical Safety Considerations
Do not use if serum potassium ≥4.5 mmol/L or eGFR <45 mL/min/1.73m² due to hyperkalemia risk. 3
Monitor for gynecomastia, which is more common with spironolactone than the alternative agent eplerenone. 2
Approximately 70% of adults with resistant hypertension are candidates for mineralocorticoid receptor antagonists based on potassium and eGFR criteria. 3
Alternative Agents if Spironolactone Cannot Be Used
If spironolactone is contraindicated or not tolerated:
Eplerenone (50-200 mg daily) is the first alternative, with less gynecomastia but requiring higher dosing for equivalent blood pressure reduction. 3, 2
Amiloride is a second alternative, with one placebo-controlled trial finding it more effective than spironolactone for resistant hypertension. 2, 3
Other options include doxazosin, beta-blockers (preferably vasodilating types like nebivolol or carvedilol), or clonidine, in order of preference. 3, 2