Roxadustat Fails to Reduce Infarct Size in STEMI Patients Post-PCI: JAMA

The phase 2 randomized clinical trial, published in JAMA Network Open, evaluated whether roxadustat, an oral hypoxia-inducible factor (HIF) prolyl hydroxylase inhibitor, could limit myocardial damage following reperfusion in patients with ST-segment elevation myocardial infarction (STEMI). Preclinical evidence suggests that stabilising HIF may help protect heart tissue against reperfusion injury.

The study was conducted by Weiwei Quan, Department of Cardiology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China, and colleagues.

The Effect of Roxadustat in Acute Myocardial Infarction (ROXAMI) trial enrolled 158 adults with STEMI undergoing primary PCI at a tertiary medical centre between April 2021 and March 2024. Participants were randomly assigned to receive either oral roxadustat at a dose of 100 mg three times weekly for two weeks, starting within two hours after PCI, or standard care alone. Follow-up continued for up to one year.

The primary outcome was infarct size as a percentage of the left ventricle at 30 days, assessed using positron emission tomography and magnetic resonance imaging.

The analysis revealed the following findings:

• No significant reduction in infarct size: Among 148 patients with evaluable imaging, infarct size averaged 23.3% of the left ventricle in the roxadustat group and 22.0% in the control group. The 1.3-percentage-point difference was not statistically significant (P = 0.51).
• Fewer cardiovascular events, but no significant difference: Major adverse cardiovascular events occurred in 3.8% of patients receiving roxadustat and 8.9% of controls. However, the difference was not statistically significant.
• Potential improvement in ventricular function: At 12 months, left ventricular ejection fraction increased by 3.4 percentage points in the roxadustat group, compared with 0.5 percentage points in the control group. The adjusted between-group difference was 2.9 percentage points.
• Possible benefit in ventricular remodelling: Left ventricular end-diastolic volume index increased less in the roxadustat group than in controls, with an adjusted between-group difference of −4.5 mL/m² at 12 months.
• Comparable safety outcomes: The incidence of prespecified safety events did not differ significantly between the groups.

The researchers cautioned that secondary findings on ventricular function and remodelling were exploratory and not adjusted for multiple comparisons, warranting confirmation in further studies. Limitations included the small sample size, which may have limited statistical power for secondary outcomes, and missing primary outcome imaging data for 10 participants, although imputation analyses yielded consistent results.

The researchers concluded that roxadustat administered after PCI did not significantly reduce infarct size at 30 days in patients with STEMI. Larger, adequately powered trials are needed to assess its potential effects on ventricular remodelling and other clinical outcomes following acute myocardial infarction.