A Game Changer for Resistant Hypertension: The Rise of Aprocitentan

J Cardiovasc Pharmacol. 2025 May 1;85(5):312-315. doi: 10.1097/FJC.0000000000001679.

Abstract

Hypertension is a major risk factor for cardiovascular disease, and a major contributor to global morbidity and mortality. In particular, resistant hypertension (rHTN), defined as blood pressure that remains elevated despite treatment with at least three antihypertensive agents including a diuretic, continues to be a major pharmacotherapeutic challenge. Traditional antihypertensive drugs often fail in patients with rHTN, underscoring the need for novel therapies. This is a brief mini-review of aprocitentan, a new drug that promises a glimmer of hope for patients with rHTN. This drug is a dual endothelin (ET) receptor antagonist that blocks both ET A and ET B receptors. Given that these two receptors are critical players in vasotone regulation, antagonizing them, such as by aprocitentan, would be expected to significantly reduce blood pressure in patients with rHTN. Indeed, the PRECISION clinical trial demonstrated aprocitentan's superior effectiveness in reducing blood pressure in resistant patients, and the effects were sustained. Aprocitentan has been recently FDA-approved, marking a major milestone in hypertension management, offering hope for patients with difficult-to-treat hypertension.

Keywords: ACE inhibitors; cardiovascular disease; diuretics; endothelin receptor; hypertension.

Publication types

  • Review

MeSH terms

  • Animals
  • Antihypertensive Agents* / adverse effects
  • Antihypertensive Agents* / therapeutic use
  • Blood Pressure* / drug effects
  • Drug Resistance*
  • Endothelin A Receptor Antagonists* / adverse effects
  • Endothelin A Receptor Antagonists* / therapeutic use
  • Endothelin B Receptor Antagonists* / adverse effects
  • Endothelin B Receptor Antagonists* / therapeutic use
  • Humans
  • Hypertension* / diagnosis
  • Hypertension* / drug therapy
  • Hypertension* / metabolism
  • Hypertension* / physiopathology
  • Pyrimidines* / adverse effects
  • Pyrimidines* / therapeutic use
  • Receptor, Endothelin A / drug effects
  • Receptor, Endothelin A / metabolism
  • Receptor, Endothelin B / drug effects
  • Receptor, Endothelin B / metabolism
  • Signal Transduction
  • Sulfonamides* / adverse effects
  • Sulfonamides* / therapeutic use
  • Treatment Outcome

Substances

  • Antihypertensive Agents
  • Pyrimidines
  • aprocitentan
  • Endothelin A Receptor Antagonists
  • Endothelin B Receptor Antagonists
  • Sulfonamides
  • Receptor, Endothelin A
  • Receptor, Endothelin B