Supplemental Digital Content is available in the text. This study examined the dose-response characteristics of aprocitentan, a dual endothelin A/endothelin B receptor antagonist, in patients with essential hypertension. In a randomized, double-blind, parallel study design, eligible patients with a sitting diastolic blood pressure (BP) of 90–109 mm Hg received aprocitentan 5, 10, 25, or 50 mg, placebo, or lisinopril 20 mg as a positive control once daily for 8 weeks. Multiple automated office BP readings were obtained with patients resting unattended (unattended automated office BP) at baseline, weeks 2, 4, and 8. Ambulatory BP was monitored for 24 hours at baseline and week 8. After a single-blind placebo run-in period, 490 eligible patients were randomized to the double-blind phase, with 409 patients completing 8 weeks of therapy per protocol. Aprocitentan 10, 25, and 50 mg decreased sitting systolic/diastolic unattended automated office BP from baseline to week 8 (placebo-corrected decreases: 7.05/4.93, 9.90/6.99, and 7.58/4.95 mm Hg, respectively, P≤0.014 versus placebo), compared with an unattended automated office BP reduction of 4.84/3.81 mm Hg with lisinopril 20 mg. For patients with valid ambulatory BP, aprocitentan 10, 25, and 50 mg significantly decreased placebo-corrected 24-hour BP by 3.99/4.04, 4.83/5.89, and 3.67/4.45 mm Hg, respectively. Incidence of adverse events was similar in the aprocitentan groups (22.0%–40.2%) and the placebo group (36.6%). Aprocitentan produced dose-dependent decreases in hemoglobin, hematocrit, albumin, and uric acid, an increase in estimated plasma volume, but no change in weight versus placebo. These findings support further investigation of aprocitentan at doses of 10 to 25 mg in hypertension. Registration— URL: https://www.clinicaltrials.gov; Unique identifier: NCT02603809.

中文翻译：

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新的双内皮素受体拮抗剂 Aprocitentan 在高血压中的随机剂量反应研究

补充数字内容在文本中可用。本研究检查了 aprocitentan（一种双重内皮素 A/内皮素 B 受体拮抗剂）在原发性高血压患者中的剂量反应特征。在一项随机、双盲、平行研究设计中，坐位舒张压 (BP) 为 90-109 mmHg 的合格患者接受阿普西替坦 5、10、25 或 50 毫克、安慰剂或赖诺普利 20 毫克作为阳性每天控制一次，持续 8 周。在基线、第 2 周、第 4 周和第 8 周，在无人值守的情况下获得多个自动诊室血压读数（无人值守自动诊室血压）。在基线和第 8 周监测动态血压 24 小时。单盲安慰剂导入后在此期间，490 名符合条件的患者被随机分配到双盲阶段，其中 409 名患者完成了每个方案 8 周的治疗。从基线到第 8 周，Aprocitentan 10、25 和 50 mg 降低了坐姿收缩压/舒张压无人值守自动办公室血压（安慰剂校正的降低：分别为 7.05/4.93、9.90/6.99 和 7.58/4.95 mmHg，P≤0.014） )，与使用赖诺普利 20 毫克的无人值守自动办公室血压降低 4.84/3.81 毫米汞柱相比。对于动态血压有效的患者，aprocitentan 10、25 和 50 mg 分别使安慰剂校正的 24 小时血压显着降低 3.99/4.04、4.83/5.89 和 3.67/4.45 mmHg。aprocitentan 组 (22.0%–40.2%) 和安慰剂组 (36.6%) 的不良事件发生率相似。Aprocitentan 导致血红蛋白、血细胞比容、白蛋白和尿酸的剂量依赖性降低，估计血浆体积增加，但与安慰剂相比，体重没有变化。这些发现支持进一步研究 10 至 25 毫克剂量的 aprocitentan 治疗高血压。注册——网址：https://www.clinicaltrials.gov；唯一标识符：NCT02603809。