Flack John M, Schlaich Markus P, Weber Michael A, Sassi-Sayadi Mouna, Narkiewicz Krzysztof, Clozel Martine, Dreier Roland F, Andrawis Nabil S, Danaietash Parisa, Gabra Nashwa, Scott David, Wang Ji-Guang, Ferdinand Keith C
Division of General Internal Medicine, Hypertension Section, Departments of Medicine and Population Science and Policy, Hypertension Section, Southern Illinois University School of Medicine, Springfield, IL (J.M.F.).
Dobney Hypertension Centre, Medical School - Royal Perth Hospital Unit, University of Western Australia, Australia (M.P.S.).
Hypertension. 2025 Apr;82(4):601-610. doi: 10.1161/HYPERTENSIONAHA.124.24142. Epub 2025 Jan 22.
Black individuals frequently present with resistant hypertension and disproportionately increased cardiovascular risk. We investigated the blood pressure (BP)-lowering effect of the dual endothelin receptor antagonist aprocitentan in Black individuals enrolled in the PRECISION study (Parallel-Group, Phase 3 Study with Aprocitentan in Subjects with Resistant Hypertension).
Patients with confirmed resistant hypertension were randomized to aprocitentan 12.5 mg, 25 mg, or placebo for 4 weeks (part 1). They subsequently received aprocitentan 25 mg for 32 weeks (part 2) before re-randomization to aprocitentan 25 mg or placebo (part 3).
Eighty-two patients randomized in the PRECISION study were Black individuals. At week 4, aprocitentan 12.5 and 25 mg reduced office trough systolic BP (-11.3 and -11.9 mm Hg) to a similar degree as placebo (-12.0 mm Hg). Using 24-hour ambulatory BP monitoring, the placebo effect was minimal (-0.7 mm Hg), and aprocitentan reduced systolic BP by 4.0 and 8.6 mm Hg. During part 2, office BP continued to decrease (-16.4 mm Hg at week 36). In part 3, office and ambulatory systolic BP increased on placebo (+9.9 and +8.1 mm Hg, respectively), whereas the BP-lowering effect was maintained with aprocitentan. Aprocitentan markedly reduced albuminuria during the study. The most frequent adverse event was peripheral edema, occurring in 3 patients (10%) receiving aprocitentan 25 mg versus none receiving aprocitentan 12.5 mg or placebo.
Aprocitentan reduced BP and albuminuria in Black individuals with resistant hypertension. The BP-lowering efficacy was similar to that of the overall PRECISION population. Aprocitentan may represent an important addition to the often difficult-to-control hypertension in Black individuals.
URL: https://www.clinicaltrials.gov; Unique identifier: NCT03541174.
黑人个体经常出现顽固性高血压，心血管风险不成比例地增加。我们在参与PRECISION研究（阿曲生坦治疗顽固性高血压的平行组3期研究）的黑人个体中，研究了双重内皮素受体拮抗剂阿曲生坦的降压效果。
确诊为顽固性高血压的患者被随机分为阿曲生坦12.5毫克、25毫克组或安慰剂组，为期4周（第1部分）。随后他们接受阿曲生坦25毫克治疗32周（第2部分），之后再次随机分为阿曲生坦25毫克组或安慰剂组（第3部分）。
PRECISION研究中随机分组的82例患者为黑人个体。在第4周时，阿曲生坦12.5毫克和25毫克组降低诊室谷值收缩压（分别为-11.3和-11.9毫米汞柱）的程度与安慰剂组（-12.0毫米汞柱）相似。使用24小时动态血压监测，安慰剂效应最小（-0.7毫米汞柱），阿曲生坦使收缩压降低了4.0和8.6毫米汞柱。在第2部分期间，诊室血压持续下降（第36周时为-16.4毫米汞柱）。在第3部分中，安慰剂组的诊室和动态收缩压均升高（分别为+9.9和+8.1毫米汞柱），而阿曲生坦维持了降压效果。在研究期间，阿曲生坦显著降低了蛋白尿。最常见的不良事件是外周水肿，3例接受阿曲生坦25毫克的患者出现外周水肿（10%），而接受阿曲生坦12.5毫克或安慰剂的患者均未出现。
阿曲生坦降低了黑人顽固性高血压患者的血压和蛋白尿。降压疗效与PRECISION研究总体人群相似。阿曲生坦可能是黑人个体中通常难以控制的高血压治疗的重要补充药物。
