Aprocitentan Reduces Blood Pressure in Black Adults with Resistant HTN: Daily Dose

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On April 9, 2025, we reported on a new study published in Hypertension that examined the blood pressure (BP)-lowering effect of the dual endothelin receptor antagonist aprocitentan in Black adults enrolled in the PRECISION study (Parallel-Group, Phase 3 Study with Aprocitentan in Subjects with Resistant Hypertension).

The study

In the PRECISION phase 3 clinical trial, (NCT03541174), participants were randomly assigned to receive either aprocitentan 12.5 mg, 25 mg, or placebo once daily during a 4-week double-blind period (part 1), followed by a 32-week single-arm period (part 2) during which all patients received aprocitentan 25 mg. At baseline, included participants had a seated systolic BP (SBP) of 140 mm Hg or greater despite treatment with at least 3 antihypertensive medications from different classes within the year prior to enrollment. The preplanned analysis included 82 PRECISION participants who self-identified as Black.

The findings

In part 1, the least-squares mean reduction in office SBP at trough level was –11.3 mm Hg (12.5 mg), –11.19 mm Hg (25 mg), and –12.0 mm Hg (placebo). However, 24-hour ambulatory systolic BP monitoring demonstrated dose-dependent decreases at week 4 in aprocitentan-treated participants of –4.0 mm Hg (12.5 mg), –8.6 mm Hg (25 mg), and –0.7 mm Hg (placebo). The BP lowering effect was observed during both day and nighttime monitoring, the authors said. In part 2, the mean systolic BP reduction from baseline continued, reaching 16.4 mm Hg at week 36.

Notably, aprocitentan reduced urinary albumin-to-creatinine ratio (UACR) by approximately 38% (12.5 mg) and 65% (25 mg) at week 4 in patients with micro- or macroalbuminuria, compared to a 13% reduction in the placebo group, reductions in proteinuria that were sustained throughout part 2 of the study.

Authors' comments

"Aprocitentan may represent a new therapeutic approach with an additional mechanism of action particularly fitting the pathophysiology of hypertension in Black adults with uncontrolled drug-treated hypertension."

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