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Clinical Pearls on Resistant Hypertension



Clinical Pearls on Resistant Hypertension

Ali Ibrahim Ali Rahil, MBChB, ABIM, MRCP (UK), FRCP (Edinburgh), MRCP
(Endocrine), PGDip DM (UK)
Senior Consultant, Internal Medicine, HMC
Assistant Professor, Clinical Medicine, WCM-Q
Associate Professor, Clinical Medicine, QU

 

Hypertension has become more prevalent following a recent change in its definition, which lowered the threshold from a cutoff of 140/90 mmHg to 130/80 mmHg, as defined by the AHA/ACC guidelines. This change was based on the landmark “SPRINT” trial, which demonstrated significant benefits from intensively reducing systolic blood pressure (SBP) to below 120 mmHg compared to SBP levels below 140 mmHg. Consequently, the prevalence of hypertension in the United States has increased from 32% to 47%, leading to a higher expected rate of resistant hypertension (RH).

RH is defined as a BP of 130/80 mmHg or more despite the use of at least three antihypertensive medications, including thiazide or thiazide-like diuretics, administered at appropriate and maximally tolerated dosages. If a patient is using four medications to control BP, it is called controlled resistant hypertension. Refractory hypertension is labeled when BP remains uncontrolled despite the use of five medications.

It is important to confirm office BP readings with out-of-office measurements, either through home BP (HBPM) or, preferably, through ambulatory BP measurement (ABPM). Most patients who are labeled as having RH have what is known as pseudo-resistant hypertension, which encompasses a lack of adherence to antihypertensive medications and incorrect BP measurement techniques or settings.

Management of RH requires a systematic approach that includes:

  • Confirming the diagnosis and excluding pseudo-resistance by:
  • Verifying medication adherence
  • Ensuring accurate BP measurement techniques and frequency
  • Conducting out-of-office BP measurements (HBPM or ABPM)
  • Optimizing lifestyle factors that may contribute to elevated BP
  • Investigating secondary causes of hypertension, including:
  • Primary aldosteronism
  • Obstructive sleep apnea (OSA)
  • Chronic kidney disease
  • Renovascular hypertension (renal artery stenosis)
  • Other endocrine disorders, such as pheochromocytoma and Cushing syndrome.

The treatment of RH involves excluding apparent RH and following a multidisciplinary approach that includes:

  • Lifestyle changes, such as reducing salt intake, following the DASH diet, engaging in regular exercise, and achieving weight reduction.
  • First-line medications, which include RAAS inhibitors, calcium channel blockers, and thiazide/thiazide-like diuretics. Based on the “PATHWAY” study, spironolactone is recommended as the fourth agent; if not tolerated, alternatives like amiloride or eplerenone can be considered. Beta-blockers, alfa blockers, or vasodilators can also be selected based on compelling indications if BP remains uncontrolled.

New and emerging antihypertensive drugs, such as aldosterone antagonists (Baxdrostat), have shown efficacy in randomized phase II trials. Endothelin receptor antagonists (Aprocitentan) have also shown benefit in PRECISION trials. Long-acting agents that target RNA, such as Zilebesiran, may be administered twice a year; however, further studies are required to assess their safety.

Devise therapy with the use of renal denervation shows promise for controlling hypertension while minimizing medication use, and its safety has been encouraging based on at least 10 years of experience.

 

References:

  • Flack, J.M., Buhnerkempe, M.G. & Moore, K.T. Resistant Hypertension: Disease Burden and Emerging Treatment Options. Curr Hypertens Rep26, 183–199 (2024).
  • Acelajado MC, Hughes ZH, Oparil S, Calhoun DA. Treatment of resistant and refractory hypertension. 2019;124(7):1061-1070.
  • Lauder L, Mahfoud F. Management of Resistant Hypertension. Annu. Rev. Med. 2024.75: 16.1-16.5
  • Schmieder R, Burnier M, East C, Tsioufis K, Delaney S. Renal Denervation: A Practical Guide for Health Professionals Managing Hypertension. Interv Cardiol. 2023 Mar 7;18:e06.
  • Raymond R Townsend, MD. Definition, risk factors and evaluation of resistant hypertension. UpToDate, Literature review current through: Nov 2024. Last updated: Sep 08, 2023.