From the Guidelines
The extent of blood pressure reduction with spironolactone is substantial, with studies showing an average reduction of 25 mm Hg systolic and 12 mm Hg diastolic 1.
Key Findings
- The antihypertensive benefit of spironolactone is similar in both African American and white patients 1.
- The blood pressure response to spironolactone is not predicted by baseline plasma aldosterone or 24-hour urinary aldosterone, plasma renin activity, or plasma aldosterone/renin ratio 1.
- Spironolactone is recommended as a fourth-line agent for the treatment of resistant hypertension, with a low dose added to the existing treatment regimen if serum potassium is <4.5 mmol/L and eGFR is >45 ml/min/1.73m2 1.
Treatment Guidelines
- The 2024 ESC guidelines recommend the addition of low-dose spironolactone to existing treatment for patients with resistant hypertension 1.
- The 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APHA/ASH/ASPC/NMA/PCNA guideline recommends the use of spironolactone as part of a multidrug regimen for the treatment of resistant hypertension 1.
- The 2020 International Society of Hypertension global hypertension practice guidelines recommend the use of spironolactone as a fourth-line agent for the treatment of resistant hypertension 1.
Important Considerations
- Spironolactone should be used with caution in patients with renal impairment or hyperkalemia 1.
- The effectiveness of spironolactone in reducing cardiovascular disease risk is still being studied, and more evidence is needed to fully understand its benefits 1.
From the FDA Drug Label
The dose response of spironolactone for hypertension has not been well characterized. In patients with hypertension, decreases in systolic blood pressure have been observed at doses ranging from 25 mg/day to 100 mg/day. Doses greater than 100 mg/day generally do not provide additional reductions in blood pressure The extent of blood pressure reduction with spironolactone is not well characterized, but decreases in systolic blood pressure have been observed at doses ranging from 25 mg/day to 100 mg/day 2.
- The exact extent of blood pressure reduction is not specified in the drug label.
- Doses greater than 100 mg/day generally do not provide additional reductions in blood pressure.
From the Research
Blood Pressure Reduction with Spironolactone
The extent of blood pressure reduction with spironolactone can be summarized as follows:
- A study published in 2003 3 found that low-dose spironolactone was associated with an additional mean decrease in blood pressure of 21 +/- 21/10 +/- 14 mm Hg at 6 weeks and 25 +/- 20/12 +/- 12 mm Hg at 6-month follow-up.
- A meta-analysis published in 2020 4 found that spironolactone significantly reduced office blood pressure (office SBP, weighted mean difference [WMD] = -20.14,95% CI = -31.17 to -9.12, P < .001; office DBP WMD = -5.73,95% CI = -8.13 to -3.33, P < .001) and 24-hour ambulatory blood pressure.
- A study published in 2007 5 found that spironolactone effectively lowered blood pressure in patients with hypertension uncontrolled by a mean of approximately 3 other drugs, with a mean blood pressure reduction of 21.9/9.5 mm Hg.
- A meta-analysis published in 2015 6 found that spironolactone resulted in a reduction in mean systolic and diastolic blood pressure of -20.56 mmHg and -6.04 mm Hg, respectively.
- Another meta-analysis published in 2017 7 found that the reduction of systolic blood pressure and diastolic blood pressure in patients treated with spironolactone was greater than placebo, with weighted mean differences of -16.67mmHg and -6.11mmHg, respectively.
Key Findings
Some key findings from these studies include:
- Spironolactone can result in a substantial blood pressure reduction in patients with resistant hypertension 4, 5, 6, 7.
- The blood pressure reduction with spironolactone is additive to the use of other antihypertensive agents, such as ACE inhibitors, ARBs, and diuretics 3.
- Spironolactone is generally well tolerated, with common adverse effects including gynecomastia or breast discomfort and biochemical abnormalities 5.