Aprocitentan the first endothelin receptor antagonist approved for treatment of hypertension

Just now, I read online that aprocitentan has become the first endothelin receptor antagonist to be approved by the USFDA for treatment of hypertension. Edema and anemia are the most common adverse events as per the manufacturer’s prescribing information and aprocitentan is contraindicated in pregnancy. Edema could be managed by adding or uptitrating diuretics.

Macitentan used in the treatment of pulmonary arterial hypertension, metabolizes into the active compound, aprocitentan. Aprocitentan is an orally active, dual endothelin receptor antagonist which inhibits ET‐1 by binding to both ETA and ETB receptors. Aprocitentan enhances the antihypertensive effect of other antihypertensive drugs including renin-angiotensin-sytem blockers  [1].

PRECISION was a phase 3 trial of aprocitentan which had centres from Europe, North America, Asia, and Australia participating [1]. It was a blinded randomised parallel group study. Those with systolic blood pressure 140 mm Hg or more in sitting position while on three antihypertensive drugs including a diuretic were enrolled. 577 of the 730 patients completed part 3 of the study. The study concluded that in resistant hypertension, aprocitentan was well tolerated and superior to placebo in lowering blood pressure at 4 weeks, with a sustained effect noted at 40th week.

References

1. Angeli F, Verdecchia P, Reboldi G. Aprocitentan, A Dual Endothelin Receptor Antagonist Under Development for the Treatment of Resistant Hypertension. Cardiol Ther. 2021 Dec;10(2):397-406. doi: 10.1007/s40119-021-00233-7. Epub 2021 Jul 12. PMID: 34251649; PMCID: PMC8555037.
2. Schlaich MP, Bellet M, Weber MA, Danaietash P, Bakris GL, Flack JM, Dreier RF, Sassi-Sayadi M, Haskell LP, Narkiewicz K, Wang JG; PRECISION investigators. Dual endothelin antagonist aprocitentan for resistant hypertension (PRECISION): a multicentre, blinded, randomised, parallel-group, phase 3 trial. Lancet. 2022 Dec 3;400(10367):1927-1937. doi: 10.1016/S0140-6736(22)02034-7. Epub 2022 Nov 7. Erratum in: Lancet. 2023 Jan 28;401(10373):268. PMID: 36356632.