Resistant and Refractory Hypertension: Antihypertensive Treatment Resistance vs Treatment Failure

Can J Cardiol. 2016 May;32(5):603-6. doi: 10.1016/j.cjca.2015.06.033. Epub 2015 Jul 8.


Resistant or difficult to treat hypertension is defined as high blood pressure that remains uncontrolled with 3 or more different antihypertensive medications, including a diuretic. Recent definitions also include controlled blood pressure with use of 4 or more medications as also being resistant to treatment. Recently, refractory hypertension, an extreme phenotype of antihypertensive treatment failure has been defined as hypertension uncontrolled with use of 5 or more antihypertensive agents, including a long-acting thiazide diuretic and a mineralocorticoid receptor antagonist. Patients with resistant vs refractory hypertension share similar characteristics and comorbidities, including obesity, African American race, female sex, diabetes, coronary heart disease, chronic kidney disease, and obstructive sleep apnea. Patients with refractory vs resistant hypertension tend to be younger and are more likely to have been diagnosed with congestive heart failure. Refractory hypertension might also differ from resistant hypertension in terms of underlying cause. Preliminary evidence suggests that refractory hypertension is more likely to be neurogenic in etiology (ie, heightened sympathetic tone), vs a volume-dependent hypertension that is more characteristic of resistant hypertension in general.

Publication types

  • Comparative Study

MeSH terms

  • Antihypertensive Agents / pharmacology
  • Antihypertensive Agents / therapeutic use*
  • Blood Pressure / drug effects
  • Diuretics / pharmacology
  • Diuretics / therapeutic use*
  • Drug Resistance
  • Humans
  • Hypertension / drug therapy*
  • Hypertension / epidemiology
  • Hypertension / etiology
  • Hypertension / physiopathology*
  • Prevalence
  • Risk Factors
  • Sympathetic Nervous System / physiopathology
  • Treatment Failure
  • United States / epidemiology


  • Antihypertensive Agents
  • Diuretics