Drug Therapy for Resistant Hypertension: Simplifying the Approach

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. J Clin Hypertens (Greenwich). 2011;13:120–130. © 2010 Wiley Periodicals, Inc.