Drug Therapy for Resistant Hypertension: Simplifying the Approach Review uri icon


MeSH Major

  • Antihypertensive Agents
  • Drug Resistance
  • Hypertension


  • Despite the availability of many effective antihypertensive drugs, the drug therapy for resistant hypertension remains a prominent problem. Reviews offer only the general recommendations of increasing dosage and adding drugs, offering clinicians little guidance with respect to the specifics of selecting medications and dosages. A simplified decision tree for drug selection that would be effective in most cases is needed. This review proposes such an approach. The approach is mechanism-based, targeting treatment at three hypertensive mechanisms: (1) sodium/volume, (2) the renin-angiotensin system (RAS), and (3) the sympathetic nervous system (SNS). It assumes baseline treatment with a 2-drug combination directed at sodium/volume and the RAS and recommends proceeding with one or both of just two treatment options: (1) strengthening the diuretic regimen, possibly with the addition of spironolactone, and/or (2) adding agents directed at the SNS, usually a β-blocker or combination of an α- and a β-blocker. The review calls for greater research and clinical attention directed to: (1) assessment of clinical clues that can help direct treatment toward either sodium/volume or the SNS, (2) increased recognition of the role of neurogenic (SNS-mediated) hypertension in resistant hypertension, (3) increased recognition of the effective but underutilized combination of α- + β-blockade, and (4) drug pharmacokinetics and dosing.

publication date

  • February 2011



  • Review



  • eng

Digital Object Identifier (DOI)

  • 10.1111/j.1751-7176.2010.00387.x

PubMed ID

  • 21272200

Additional Document Info

start page

  • 120

end page

  • 30


  • 13


  • 2