Spironolactone for Resistant Hypertension

Year in Review |
December 30, 2015

Spironolactone for Resistant Hypertension

  1. Bruce Soloway, MD

Spironolactone was the most effective add-on therapy for patients with three-drug–resistant hypertension.

  1. Bruce Soloway, MD

Current hypertension guidelines recommend a thiazide diuretic, a calcium-channel blocker, and an angiotensin-converting enzyme inhibitor or an angiotensin-receptor blocker, singly or in combination, to achieve target blood pressure (BP). Resistant hypertension — defined as uncontrolled BP despite treatment with medications from all three classes — is estimated to occur in at least 10% of treated hypertensive patients and carries excess risk for adverse cardiovascular outcomes. In a 2015 meta-analysis, researchers found that aldosterone antagonists were safe and effective for patients with resistant hypertension (Am J Hypertens 2015; 28:1376), but little is known about the comparative effectiveness of other potential treatments.

Researchers in the U.K. enrolled 314 patients with resistant hypertension (mean baseline BP, 157/90 mm Hg in the clinic and 148/84 mm Hg at home), continued their baseline three-drug antihypertensive therapy, and added four additional once-daily medications for 12 weeks each in random order: spironolactone (25 and 50 mg), bisoprolol (5 and 10 mg), doxazosin (4 and 8 mg), and placebo. For each medication, patients took the lower dose for 6 weeks and then the higher dose for 6 weeks. Outcomes were assessed by averaging multiple home BP readings. Plasma renin activity (PRA) was measured for each patient at baseline.

Spironolactone significantly lowered average home systolic BP by 8.7 mm Hg compared to placebo, 4.5 mm Hg compared to bisoprolol, and 4.0 mm Hg compared to doxazosin. Spironolactone was the most effective treatment throughout the range of baseline PRA, but its advantage was greatest for patients with low PRA. Adverse effects were uncommon and similar during all treatment phases.

The greater effectiveness of spironolactone compared with other agents, particularly in patients with low baseline PRA levels, suggests that sodium retention is a major cause of resistant hypertension, perhaps caused by inadequate diuretic therapy or undiagnosed hyperaldosteronism. Although exposure to each drug in this study was brief and clinical outcomes were not measured, these data suggest that spironolactone usually would be the preferred next choice when a combination of the three standard drug classes for hypertension has failed to lower BP adequately (NEJM JW Gen Med Oct 15 2015 and Lancet 2015; 386:2059). However, spironolactone should be avoided in patients with substantial renal impairment to minimize risk for hyperkalemia (patients with glomerular filtration rates <45 mL/minute/1.73 m2 were excluded from this study).

Editor Disclosures at Time of Publication

  • Disclosures for Bruce Soloway, MD at time of publication Nothing to disclose

Reader Comments (4)

LEOPOLDO PEREZ Nurse/NP/PA, Family Medicine/General Practice, Private Office, Miami

I have followed this recommendation with Spironolactone for years, with very good results, of course, monitoring K levels.

Diana Monsalve, Cardiology NP Nurse/NP/PA, Cardiology

Very beneficial drug, potentiates diuretic well. Need to monitor K, recommended with initial addition is check K at 3 days, then 7 days. I am always cautious with decreased kidney function.


Did you monitor serum Potassium and if so how often.

Luis Pires Gonçalves Physician, Internal Medicine, Lisboa

This is real advance

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