Single-Pill Low-Dose Triple Combination Therapy vs Standard-Dose Monotherapy in Patients With Mild-to-Moderate Hypertension.

Although previous phase II and pragmatic studies suggested promise, these are the first phase III, double-blind, active-controlled trials comparing a single-pill ultra-low-dose triple combination with standard-dose monotherapy.

尽管之前的II期和实用性研究显示出了希望，但这些是首次进行的III期、双盲、活性对照试验，比较了单片超低剂量三联疗法与标准剂量单药治疗。

In these studies, we sought to compare a single-pill combination of 1.67 mg amlodipine, 16.67 mg losartan potassium, and 4.17 mg chlorthalidone (LDC-ALC) with standard-dose monotherapy-5 mg amlodipine or 50 mg losartan potassium-in patients with mild-to-moderate hypertension.

在这项研究中，我们试图比较一种单片复方药物，包含1.67毫克氨氯地平、16.67毫克洛沙坦钾和4.17毫克氯噻酮（LDC-ALC），与标准剂量的单一药物治疗——5毫克氨氯地平或50毫克洛沙坦钾——在轻度至中度高血压患者中的效果。

Methods

HM-APOLLO-301 (Study 301, May 2022-June 2023) and HM-APOLLO-302 (Study 302, March-December 2024) were multicenter, randomized, double-blind, active-controlled, phase III studies in South Korea.

HM-APOLLO-301（研究301，2022年5月至2023年6月）和HM-APOLLO-302（研究302，2024年3月至2024年12月）是在韩国进行的多中心、随机、双盲、活性对照的III期研究。

Study 301 compared LDC-ALC and amlodipine; Study 302 compared LDC-ALC and losartan.

研究301比较了LDC-ALC与氨氯地平；研究302比较了LDC-ALC与洛沙坦。

Adults (≥19 years of age) with systolic blood pressure (SBP) 140 to <180 mm Hg and diastolic blood pressure (DBP) <110 mm Hg after 4-week placebo run-in were randomized to 8 weeks of treatment.

在为期4周的安慰剂导入期后，将收缩压（SBP）为140至<180毫米汞柱且舒张压（DBP）<110毫米汞柱的成年人（≥19岁）随机分配接受8周治疗。

The primary endpoint was SBP reduction at week 8, assessed first for noninferiority, then for superiority.

主要终点是第8周的收缩压(SBP)降低，首先评估非劣效性，然后评估优效性。

Results

In Study 301, LDC-ALC exhibited noninferiority to amlodipine in reducing SBP at week 8 (upper bound of 1-sided 97.5% CI: 2.8 mm Hg [<3 mm Hg noninferiority margin]), and similar efficacy (least-squares mean change: -19.1 vs -19.9 mm Hg; 95% CI: -1.5 to 3.1; P = 0.495), with similar DBP reduction and blood pressure control rate.

在第301研究中，LDC-ALC在第8周降低SBP方面显示出与氨氯地平的非劣效性（单侧97.5%置信区间上限：2.8毫米汞柱[<3毫米汞柱非劣效性边界]），并且疗效相似（最小二乘平均变化：-19.1 vs -19.9毫米汞柱；95%置信区间：-1.5到3.1；P = 0.495），舒张压(DBP)降低和血压控制率相似。

In Study 302, LDC-ALC was both noninferior (upper bound of one-sided 97.5% CI: -0.6 mm Hg) and superior to losartan (least-squares mean change: -19.9 vs -16.4 mm Hg; 95% CI: -6.6 to -0.2; P = 0.037) in SBP reduction at week 8, with greater DBP reduction and a higher blood pressure control rate than losartan.

在研究302中，LDC-ALC在第8周时降低收缩压（SBP）方面既非劣效（单侧97.5%置信区间上限：-0.6毫米汞柱），又优于洛沙坦（最小二乘平均变化：-19.9毫米汞柱对比-16.4毫米汞柱；95%置信区间：-6.6至-0.2；P = 0.037），并且与洛沙坦相比，LDC-ALC在降低舒张压（DBP）和血压控制率方面表现更佳。

Adverse events were similar between groups (LDC-ALC vs amlodipine: 11.7% vs 13.9%; LDC-ALC vs losartan: 6.4% vs 3.3%), with ≤1% treatment withdrawals and no serious drug-related events.

两组间不良事件发生率相似（LDC-ALC对比氨氯地平：11.7%对比13.9%；LDC-ALC对比洛沙坦：6.4%对比3.3%），治疗撤回率≤1%，且没有严重与药物相关的事件。

Conclusions

Single-pill LDC-ALC achieved BP reductions similar to those with amlodipine and greater than those with losartan monotherapy over 8 weeks, with similar short-term tolerability.

单片LDC-ALC在8周内实现了与氨氯地平相似的血压降低效果，并且超过了洛沙坦单药治疗的效果，短期耐受性相似。

These findings support LDC-ALC as an effective and well tolerated alternative initial therapy for mild-to-moderate hypertension, expanding the set of validated strategies alongside established monotherapies.

这些发现支持LDC-ALC作为一种有效且耐受性良好的轻中度高血压初始治疗替代方案，扩大了与已建立的单药治疗并行的有效策略集合。

(A Study to Evaluate Efficacy and Safety of HCP1803 in Patients With Essential Hypertension [HM-APOLLO-301; NCT05362110]; A Study to Evaluate Efficacy and Safety of HCP1803 Compared to RLD2001-1 in Patients with Essential Hypertension [HM-APOLLO-302, NCT06438172]).

(一项评估HCP1803在原发性高血压患者中的疗效和安全性的研究[HM-APOLLO-301; NCT05362110]; 一项评估HCP1803与参比药物RLD2001-1在原发性高血压患者中的疗效和安全性比较的研究[HM-APOLLO-302, NCT06438172])。