Physicians' Academy for Cardiovascular Education

Dual endothelin A and B receptor antagonist reduces office SBP in resistant hypertension

News - Nov. 9, 2022

Sustained Blood Pressure Lowering Effect With the Dual Endothelin Receptor Antagonist Aprocitentan in Resistant Hypertension: Results From a Randomized, Controlled Study Including a Withdrawal Phase

Presented at the AHA Scientific Sessions 2022 by: Prof. Markus Schlaich, MD- Perth, Australia

Introduction and methods

Resistant hypertension is defined by the inability to regulate blood pressure with 3 or more drug classes including inhibitors of the RAAS system (ACEi or ARB), calcium channel blockers and diuretics. The preferred fourth option for treatment of resistant hypertension is the MRA spironolactone that targets aldosterone.

However, failure of BP control with these currently available medications suggests that there are relevant pathophysiologic pathways that are not targeted, one of them possibly being the endothelin (ET) pathway. Indeed, ET has been implicated in the pathogenesis of hypertension by regulating water and sodium retention. ET exerts its BP-raising effect via vasoconstriction of VSMC and stimulation of aldosterone secretion.

In the PRECISION phase 3 trial, a dual ET A en B receptor antagonist (ERA) named aprocitentan was examined in patients with resistant hypertension.

Patients were screened on individual background anti-hypertensive medication if their BP was uncontrolled and then switched to standardized background therapy for 4 weeks. Eligible patients underwent a run-in period on placebo for 4 weeks followed by a first randomized phase. Patients were randomized to placebo (n=242), aprocitentan 12.5 mg (n=243) or aprocitentan 25 mg (n=245) for 4 weeks in the first part of the study. All patients then received aprocitentan 25 mg for 32 weeks (part 2) and were re-randomized to aprocitentan 25 mg or placebo for 12 weeks in part 3 (withdrawal phase). During the complete trial they stayed on standard background therapy. They were followed for an additional 30 days.

The primary endpoint was change from baseline tot week 4 in mean trough sitting office SBP.

Main results


Aprocitentan lowered office SBP and 24-h ambulatory SBP compared with placebo at 4 weeks in patients with resistant hypertension. BP lowering was maintained over 48 weeks. The most common adverse event was edema/fluid retention within the first 4 weeks of treatment.

- Our reporting is based on the information provided at the AHA Scientific Sessions 2022 -

The findings of the PRECISION trial were simultaneously published in The Lancet.

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