Controversies in Hypertension V: Resistant and Refractory Hypertension

Am J Med. 2024 Jan;137(1):12-22. doi: 10.1016/j.amjmed.2023.09.015. Epub 2023 Oct 12.

Abstract

Apparent resistant hypertension, defined as uncontrolled office blood pressure despite ≥ 3 antihypertensive medications including a diuretic or use of ≥ 4 medications regardless of blood pressure, occurs in ≤ 15% of treated hypertensives. Apparent refractory hypertension, defined as uncontrolled office pressure despite use of 5 or more medications including a diuretic, occurs in ≤ 10% of resistant cases. Both are associated with increased comorbidity and enhanced cardiovascular risk. To rule out pseudo-resistant or pseudo-refractory hypertension, employ guideline-based methodology for obtaining pressure, maximize the regimen, rule out white-coat effect, and assess adherence. True resistant hypertension is characterized by volume overload and aldosterone excess, refractory by enhanced sympathetic tone. Spironolactone is the preferred agent for resistance, with lower doses. Spironolactone, potassium binders, or both, are preferred if the estimated glomerular filtration rate is below 45. If significant albuminuria, finerenone is indicated. The optimal treatment of refractory hypertension is unclear, but sympathetic inhibition (α-β blockade, centrally acting sympathoinhibitors, or both) seems reasonable. Renal denervation has shown minimal benefit for resistance, but its role in refractory hypertension remains to be defined.

Keywords: Ambulatory blood pressure monitoring; Finerenone; Home blood pressure monitoring; Hypertension; Mineralocorticoid receptor antagonists; Refractory hypertension; Renal denervation; Resistant hypertension; Spironolactone.

Publication types

  • Review

MeSH terms

  • Antihypertensive Agents / pharmacology
  • Antihypertensive Agents / therapeutic use
  • Blood Pressure
  • Blood Pressure Monitoring, Ambulatory
  • Diuretics / therapeutic use
  • Humans
  • Hypertension* / drug therapy
  • Spironolactone* / therapeutic use

Substances

  • Spironolactone
  • Antihypertensive Agents
  • Diuretics