Roxadustat Treatment After PCI Among Patients With ST-Segment Elevation Myocardial Infarction: A Randomized Clinical Trial.

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.