Resistant Hypertension: Mechanisms and Treatment

Curr Hypertens Rep. 2017 Jul;19(7):56. doi: 10.1007/s11906-017-0754-x.


Purpose of review: Emerging evidence suggests that multiple mechanisms may be responsible for the development of treatment-resistant hypertension (TRH). This review aims to summarize recent data on potential mechanisms of resistance and discuss current pharmacotherapeutic options available in the management of TRH.

Recent findings: Excess sodium and fluid retention, increased activation of the renin-angiotensin-aldosterone system, and heightened activity of the sympathetic nervous system appear to play an important role in development of TRH. Emerging evidence also suggests a role for arterial stiffness and, potentially, gut dysbiosis. Therapeutic approaches for TRH should include diuretic optimization and the addition of aldosterone antagonists as the preferred fourth agent in most patients. Further therapeutic approaches may be guided by the suspected underlying mechanism of TRH in conjunction with other patient-specific factors. The pathophysiology of TRH is multifaceted; however, increasing evidence supports several mechanisms that may be targeted to improve blood pressure control among patients with TRH. Further studies are needed to determine whether such approaches may be more effective than usual care.

Keywords: Antihypertensive; Mechanisms; Resistant hypertension; Treatment.

Publication types

  • Review

MeSH terms

  • Antihypertensive Agents / therapeutic use
  • Diuretics / therapeutic use
  • Drug Resistance*
  • Humans
  • Hypertension / drug therapy*
  • Hypertension / physiopathology*
  • Mineralocorticoid Receptor Antagonists / therapeutic use
  • Renin-Angiotensin System / physiology
  • Sodium, Dietary / adverse effects
  • Sympathetic Nervous System / physiopathology
  • Water-Electrolyte Imbalance / physiopathology


  • Antihypertensive Agents
  • Diuretics
  • Mineralocorticoid Receptor Antagonists
  • Sodium, Dietary