Role of aldosterone blockade in resistant hypertension

Semin Nephrol. 2014 May;34(3):273-84. doi: 10.1016/j.semnephrol.2014.04.004. Epub 2014 Apr 28.


Apparent treatment-resistant hypertension (aTRH), defined as uncontrolled blood pressure using 3 or more antihypertensive medications or controlled using 4 or more antihypertensive medications, affects approximately 30% of uncontrolled and 12% of controlled blood pressure (BP) patients. aTRH is used when pseudoresistance cannot be excluded (eg, BP measurement artifacts, mainly office resistance, suboptimal adherence, suboptimal treatment regimens, and true TRH). True TRH comprises approximately 30% to 50% of TRH. Patients with TRH have a high prevalence of obesity, insulin resistance, sleep apnea, and volume expansion. Aldosterone, a mineralocorticoid, is an important contributor to TRH, with primary aldosteronism present in approximately 20% of patients. Spironolactone, a mineralocorticoid-receptor antagonist, as a fourth-line agent, decreases BP 20 to 25/10 to 12 mm Hg in TRH patients with and without primary aldosteronism. The BP response to spironolactone is roughly double that of other classes of antihypertensive medications in TRH. Although approximately 70% of patients with uncontrolled TRH have estimated glomerular filtration rate of 50 or greater and a serum potassium level of 4.5 or less, which are associated with a low risk for hyperkalemia, only a small percentage receive a mineralocorticoid-receptor antagonist. This review examines the clinical epidemiology and pharmacotherapy of controlled and uncontrolled hypertension with an emphasis on aTRH, the role of aldosterone in blood pressure regulation, and the potential benefits of mineralocorticoid-receptor antagonist in uncontrolled TRH.

Keywords: aldosterone; aldosterone-antagonists; hypertension; treatment resisitant hypertension.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Review

MeSH terms

  • Blood Pressure Determination
  • Clinical Trials as Topic
  • Drug Resistance
  • Glomerular Filtration Rate / drug effects
  • Humans
  • Hypertension / drug therapy*
  • Insulin Resistance
  • Kidney / metabolism
  • Medication Adherence
  • Mineralocorticoid Receptor Antagonists / therapeutic use*
  • Sodium / metabolism
  • Spironolactone / therapeutic use


  • Mineralocorticoid Receptor Antagonists
  • Spironolactone
  • Sodium