Hypertension Journal

Show Contents

Resistant Hypertension: Overview
Resistant Hypertension: Overview
K. Krishnakumar
Department of Cardiology, Senior Interventional Cardiologist, PRS Hospital, Trivandrum, Kerala, India
Address for correspondence: Dr. K. Krishnakumar, Senior Interventional Cardiologist, PRS Hospital, Trivandrum - 695 002, Kerala, India.
E-mail: krishnasarith@rediffmail.com
Received: 10-10-2018; Accepted: 01-12-2018
doi: 10.15713/ins.johtn.0147
Resistant hypertension (RH) is defined as office blood pressures (BP) which is uncontrolled on ≥3 or controlled on ≥4 differentclasses of antihypertensive medications at optimal doses and preferably including a diuretic.
  • RH is important as many patients in this subgroup have secondary causes of hypertension.
  • Most important aspect of treatment in RH is to divide RH into true RH and pseudo-RH.
  • Three factors, namely patient adherence, optimal dosing of antihypertensive medications, and out-of-office BP recordings, areimportant in classifying RH to true RH and pseudo-RH.
  • Many RH patients are volume expanded and respond to intensified diuretic therapy, sodium restriction, dual calcium-channelblocker, or α-adrenoreceptor blocker. Plasma renin activity can be used for personalized therapy in RH.
Keywords: Resistant hypertension, insulin resistance, artifacts, adherence, secondary hypertension, indapamide, valsartan, escalating diuretics,renin guided therapy
How to cite this article: Krishnakumar K. ResistantHypertension: Overview. Hypertens 2019;5(1): 32-34.
Source of support: Nil
Conflict of interest: None


Resistant hypertension (RH) is defined as blood pressures(BP) uncontrolled on ≥3 or controlled on ≥4 different classesof antihypertensive medications at optimal doses and preferablyincluding a diuretic.
  • Insulin resistance and obstructive sleep apnea are twocommon associations of RH.
  • True RH and pseudo-RH are two subsets of RH which haveto be identified and treated.

BP measurement artifacts
  • It is important to obtain accurate BP values before labelingas RH. Standard BP measurement protocols are required tosegregate true RH from apparent RH.
  • To minimize measurement artifacts.
  • To get a BP value which represents true out-of-office BP.
  • BP has to be measured accurately in office setting by trainedindividuals to avoid problem of white-coat effect.
  • Automated office BP in which a series of BP measurementsare made in office usually mimicks daytime recordings.[1]

Optimal therapy
  • It is important to define what is optimal therapy beforeclassifying patients as true RH.

What medications and what dose ?

Patient should be on three different classes of antihypertensivemedications including a diuretic.[2]

Antihypertensive dose should be =50% of maximumrecommended dose.

Patient adherence

Can be assessed by direct questions - Are you regularly takingmedications?
  • Indirect question: Regarding concern for cost or sideeffects.
  • In apparent RH, clinicians appear to have opportunitiesto improve BP control by optimizing antihypertensivemedication dosing.
  • Once a diagnosis of true RH is made, one has to evaluate forthe cause of secondary hypertension (HTN).

32 Hypertension Journal, January-March, Vol 5, 2019

Resistant hypertension a pragmatic approach Krishnakumar

Resistant Hypertension: Overview


In patients with apparent-resistant HTN based on themeasurement of office BP, the subject with nonhypertensiveout-of-office BP values has a favorable prognosis. This is whereambulatory BP recordings are useful. Both self-monitored BPand ambulatory BP recordings provide prognostically importantinformation beyond office BP, in this group of patients.[1]

Pharmacotherapy of RH

Commonly prescribed three drugs regimen for RH include ARB+ CCB + thiazide diuretic. Beta blockers could be added forspecific indications.[3]

Drugs and Dosing for RH

Resistant Hypertension: Overview


Low-dose aldosterone antagonist, spironolactone 12.5-50 mg,lowers BP in RH. Spironolactone at a dose of 25 mg daily loweredBP by 25-50 mmHg (systolic)/10-15 mmHg (diastolic).Eplerenone is an alternative aldosterone antagonist devoid of sexsteroid effects.

Beta Blockers

Aldosterone is projected to play a major role in BP regulationin long term than renin-angiotensin system.[5] Aldosteroneraises BP by increasing number and activity of epithelialsodium channels. Amiloride which is epithelial sodiumchannel blocker has similar effect as Aldosterone antagonist.

However target organ protection is seen only with Aldosteroneantagonist Patients with serum K+ value >4.5 and eGFR< 45 ml/min are not ideal candidates for spironolactone.Target organ protection is a major advantage of Aldosteroneantagonists.


Escalating diuretic potency from hydrochlorothiazideto chlorthalidone to torsemide as GFR decline from >45 to< 30 ml/1.7 m2/min helps to reduce fluid retention and helps inBP control.

Resistant Hypertension: Overview

Personalized Therapy for RH

Renin-guided therapy, i.e. Plasma renin activity (PRA), canbe used to guide antihypertensive therapy without increasingnumber of medications.[6]

Resistant Hypertension: Overview

Control of other cardiovascular risk factors is important
  • Diabetes
  • Dyslipidemia - statins have shown 36% reduction of coronaryevents.
  • Choose antihypertensive medication depening on othercompelling indications like CAD, CKD, CHF, Diabetes.


RH should be clearly defined into true RH and pseudo-RH.Screening for secondary causes is important in true resistantHTN.

Clinicans should identify and address psuedoresistance,screen for secondary hypertension, initiate changes to lifestyleand pharmacotherapy to improve BP control.

Personalized drug therapy depending on PRA may be achoice for truly RH.

Device-based therapy may evolve in future for the treatmentof RH.

  1. Salles GF, Cardoso CR, Muxfeldt ES. Prognostic influence ofoffice and ambulatory blood pressures in resistant hypertension.Arch Intern Med 2008;168:2340-6.
  2. Egan MB. Treatment resistant hypertension: A Pragmaticmanagement approach. Hypertens J 2015;1:106-10.

Hypertension Journal, January-March, Vol 5, 201933

Krishnakumar Resistant hypertension a pragmatic approach

  1. Kaplan NM. Commentary on the sixth report of the jointnational committee (JNC-6) Am J Hypertens 1998;11:134-6.
  2. Sica DA. Current concepts of pharmacotherapy in hypertension:Combination calcium channel blocker therapy in the treatmentof hypertension. J Clin Hypertens (Greenwich) 2001;3:322-7.
  3. Chapman N, Dobson J, Wilson S, Dahlof B, Sever PS, Wedel H,et al. Effect of spironolactone on blood pressure in subjects withresistant hypertension. Hypertension 2007;49:839-45.

  1. Laragh J. How to choose the correct drug for each hypertensivepatient using a plasma rennin based method. AMJ Hypertens2001;14:491-503.

34 Hypertension Journal, January-March, Vol 5, 2019