Efficacy of low-dose spironolactone in subjects with resistant hypertension

Am J Hypertens. 2003 Nov;16(11 Pt 1):925-30. doi: 10.1016/s0895-7061(03)01032-x.


Background: Previous reports have demonstrated the antihypertensive efficacy of high doses of spironolactone in subjects with primary aldosteronism and, to a lesser degree, subjects with resistant hypertension.

Methods: In current analysis, we examined the antihypertensive benefit of adding low-dose spironolactone to multidrug regimens that included a diuretic and an angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) in subjects with resistant hypertension with and without primary aldosteronism. Subjects referred for resistant hypertension were evaluated with an early morning plasma renin activity, 24-h urinary aldosterone and sodium during a high dietary salt ingestion. The diagnosis of primary aldosteronism was confirmed with a renin activity <1.0 ng/mL/h, urinary aldosterone >12 mug/24 h and urinary sodium >200 mEq/24 h. After biochemical evaluation, spironolactone (12.5 to 25 mg/d) was added to each subject's antihypertensive regimen. If blood pressure (BP) remained uncontrolled, the dose of spironolactone was titrated up to 50 mg/d. Follow-up BP was determined at 6 weeks, 3 months, and 6 months.

Results: A total number of 76 subjects were included in the analysis, 34 of whom had biochemical primary aldosteronism. Low-dose spironolactone was associated with an additional mean decrease in BP of 21 +/- 21/10 +/- 14 mm Hg at 6 weeks and 25 +/- 20/12 +/- 12 mm Hg at 6-month follow-up. The BP reduction was similar in subjects with and without primary aldosteronism and was additive to the use of ACE inhibitors, ARBs, and diuretics.

Conclusions: We conclude that low-dose spironolactone provides significant additive BP reduction in African American and white subjects with resistant hypertension with and without primary aldosteronism.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Aldosterone / blood
  • Angiotensin-Converting Enzyme Inhibitors / administration & dosage*
  • Antihypertensive Agents / administration & dosage*
  • Diuretics / administration & dosage*
  • Drug Therapy, Combination
  • Female
  • Follow-Up Studies
  • Humans
  • Hypertension / blood
  • Hypertension / drug therapy*
  • Male
  • Middle Aged
  • Renin / blood
  • Spironolactone / administration & dosage*
  • Treatment Outcome


  • Angiotensin-Converting Enzyme Inhibitors
  • Antihypertensive Agents
  • Diuretics
  • Spironolactone
  • Aldosterone
  • Renin