ST段抬高型心肌梗死患者经皮冠状动脉介入治疗后接受罗沙司他治疗：一项随机临床试验。
完整摘要 · 中文译文
重要性：临床前研究表明，稳定缺氧诱导因子（HIF）可能减轻再灌注损伤。目的：确定口服罗沙司他（一种HIF-脯氨酰羟化酶抑制剂）在ST段抬高型心肌梗死（STEMI）患者再灌注后给药是否能缩小梗死面积。设计、背景与受试者：这项2期、开放标签、随机临床试验——罗沙司他对急性心肌梗死的影响（ROXAMI）——于2021年4月1日至2024年3月31日期间在一家三级医疗中心纳入了接受直接经皮冠状动脉介入治疗（PCI）的STEMI成人患者，随访至1年。干预措施：在直接PCI后2小时内开始口服罗沙司他（100 mg，每周3次，持续2周），或仅接受标准治疗。主要结局与指标：主要终点为30天时梗死面积占左心室的百分比，通过[68Ga]Ga-DOTA-FAPI-04正电子发射断层扫描（PET）和磁共振成像（MRI）上的晚期钆增强进行测量。预设次要终点包括主要不良心血管事件、心肌损伤标志物、超声心动图参数以及[68Ga]Ga-DOTA-FAPI-04 PET和MRI上的心肌成纤维细胞活化参数。梗死面积的主要疗效分析在改良意向治疗人群中进行。结果：在158例随机分组患者中（平均[SD]年龄，63.6[11.0]岁；133例男性[84.2%]；每组随机79例），148例（93.7%；罗沙司他组72例，对照组76例）具有可评估的影像学资料用于 主要结局。对于主要终点，罗沙司他组与对照组的平均（SD）梗死面积无显著差异（23.3% [12.2%] vs 22.0% [12.2%]；平均差，1.3个百分点；95% CI，-2.7至5.3个百分点；P = .51）。罗沙司他组79例患者中有3例（3.8%）发生主要不良心血管事件，对照组79例中有7例（8.9%）（风险比，0.42；95% CI，0.11-1.63；P = .21）。在未经多重性校正的次要分析中，12个月时的校正组间差异为左心室射血分数变化2.9个百分点（95% CI，0.4-5.3个百分点；P = .02）（平均 [SD]：罗沙司他，3.4% [0.9%] vs 对照，0.5% [0.9%]），左心室舒张末期容积指数为-4.5 mL/m²（95% CI，-8.9至-0.1 mL/m²；P = .045）（平均 [SD]：罗沙司他，1.2 [1.6] mL/m² vs 对照，5.7 [1.6] mL/m²）。预设安全性终点的发生率在罗沙司他组与对照组之间无差异。 结论与意义：在这项针对STEMI患者的随机临床试验中，与对照组相比，PCI后给予罗沙司他并未在30天时显著减少梗死面积。次要心室重构结果为探索性发现，需要进一步证实。 试验注册：ClinicalTrials.gov 识别号：NCT04803864。
完整摘要 · 英文原文
IMPORTANCE: Preclinical studies suggest that stabilization of hypoxia-inducible factor (HIF) may attenuate reperfusion injury. OBJECTIVE: To determine whether oral roxadustat, a HIF-prolyl hydroxylase inhibitor, reduced infarct size when administered after reperfusion among patients with ST-segment elevation myocardial infarction (STEMI). DESIGN, SETTING, AND PARTICIPANTS: This phase 2, open-label, randomized clinical trial-Effect of Roxadustat in Acute Myocardial Infarction (ROXAMI)-enrolled adults with STEMI undergoing primary percutaneous coronary intervention (PCI) at a single tertiary medical center between April 1, 2021, and March 31, 2024, with follow-up through 1 year. INTERVENTIONS: Oral roxadustat (100 mg, 3 times per week for 2 weeks), initiated within 2 hours after primary PCI, or standard care alone. MAIN OUTCOMES AND MEASURES: The primary end point was infarct size as a percentage of the left ventricle at 30 days measured by late gadolinium enhancement on [68Ga]Ga-DOTA-FAPI-04 positron emission tomography (PET) and magnetic resonance imaging (MRI). Prespecified secondary end points included major adverse cardiovascular events, myocardial injury markers, echocardiographic parameters, and myocardial fibroblast activation parameters on [68Ga]Ga-DOTA-FAPI-04 PET and MRI. The primary efficacy analysis for infarct size was conducted in the modified intention-to-treat population. RESULTS: Among 158 randomized patients (mean [SD] age, 63.6 [11.0] years; 133 men [84.2%]; 79 randomized to each group), 148 (93.7%; 72 roxadustat and 76 control) had evaluable imaging for the primary outcome. For the primary end point, mean (SD) infarct size did not significantly differ between the roxadustat and control groups (23.3% [12.2%] vs 22.0% [12.2%]; mean difference, 1.3 percentage points; 95% CI, -2.7 to 5.3 percentage points; P = .51). Major adverse cardiovascular events occurred in 3 of 79 patients (3.8%) in the roxadustat group and 7 of 79 (8.9%) in the control group (hazard ratio, 0.42; 95% CI, 0.11-1.63; P = .21). In multiplicity-unadjusted secondary analyses, adjusted between-group differences at 12 months were 2.9 percentage points (95% CI, 0.4-5.3 percentage points; P = .02) for the change in left ventricular ejection fraction (mean [SD]: roxadustat, 3.4% [0.9%] vs control, 0.5% [0.9%]) and -4.5 mL/m2 (95% CI, -8.9 to -0.1 mL/m2; P = .045) for left ventricular end-diastolic volume index (mean [SD]: roxadustat, 1.2 [1.6] mL/m2 vs control, 5.7 [1.6] mL/m2). The incidence of prespecified safety end points did not differ between the roxadustat and control groups. CONCLUSIONS AND RELEVANCE: In this randomized clinical trial of patients with STEMI, roxadustat administration after PCI did not significantly reduce infarct size at 30 days compared with control. Secondary ventricular remodeling findings were exploratory and require confirmation. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04803864.