Aprocitentan: a new horizon in the treatment of hypertension

There has been a lack of novel medication classes approved for reducing blood pressure (BP) in hypertensive patients. Endothelins, powerful vasoconstricting peptides, have been at the forefront of experimental hypertension research since they were discovered in 1988. The recent PRECISION trial demonstrated the efficacy of aprocitentan, a novel endothelin receptor antagonist, in lowering blood pressure in patients with resistant hypertension (RH). This trial was the driving force behind the approval of aprocitentan in 2024 for the treatment of resistant hypertension.

This clinical trial review will cover the literature leading to the approval of aprocitentan and argue for its use on top of current treatments of hypertension. We argue for the need of novel anti-hypertensive medication classes and provide a brief overview of endothelin receptor antagonists. Finally, we will describe the PRECISION trial and highlight the key benefits of aprocitentan that it elucidated.

The PRECISION trial demonstrated numerous key benefits of aprocitentan, including efficacy in reducing BP and proteinuria, minimal adverse side effects, and efficacy in patients with advanced chronic kidney disease (CKD) without development of hyperkalemia. However, a lack of long-term data necessitates future investigation regarding safety. Aprocitentan may represent a novel therapeutic alternative to treat patients with RH and CKD.