The USA FDA has approved Aprocitentan (Brand name TRYVIO) for the treatment of resistant hypertension in combination with other antihypertensive drugs.
Dose: 12.5 mg 1OD PO.
MOA: Dual endothelin receptor antagonist.
Contraindications: Pregnancy, Hypersensitivity.
Adverse effects: Edema, anemia, ⬇️ sperm count.
Warning & precautions: ERAs cause hepatotoxicity & liver failure.
Trial: PRECISION was a multicentre, blinded, randomised, parallel-group, phase 3 studydone in Europe, North America, Asia & Australia in June 18, 2018, to April 25, 2022 by Prof Markus P Schlaich, MD et al.
Inclusion criteria: Patients with SBP > 140 mmhg who were on 3 different anti hypertensive medications including diuretics.
Objectives: The primary endpoints were changes in SBP from baseline to 4 week & from withdrawal baseline to 40 week. Secondary endpoints included 24-h ambulatory blood pressure changes.
Methods: Study consisted of 3 sequential parts:
Part 1 was 4-week double-blind, randomised, & placebo-controlled part, in which patients received aprocitentan 12·5 mg, 25 mg, or placebo in a 1:1:1 ratio.
Part 2 was a 32-week single patient blind part, in which all patients received aprocitentan 25 mg.
Part 3 was a 12-week double-blind, randomised, placebo-controlled withdrawal part, in which patients were re-randomised to aprocitentan 25 mg or placebo in a 1:1 ratio.
Findings: In patients with resistant hypertension, aprocitentan was well tolerated & superior to placebo in lowering blood pressure at 4 week with a sustained effect at 40 week.