Roxadustat After PCI Fails to Reduce Infarct Size in STEMI

Oral roxadustat started after primary percutaneous coronary intervention (PCI) did not reduce infarct size at 30 days in patients with ST-segment elevation myocardial infarction (STEMI), according to the phase 2 ROXAMI randomized clinical trial published in JAMA Network Open.

Preclinical studies have suggested that stabilizing hypoxia-inducible factor (HIF) may attenuate reperfusion injury. Roxadustat, an oral HIF-prolyl hydroxylase inhibitor, has been approved for treating anemia in chronic kidney disease, the authors noted. The open-label trial (NCT04803864) randomized 158 adults with STEMI undergoing primary PCI at a single center in Shanghai, China. Patients received either roxadustat 100mg 3 times weekly for 2 weeks, started within 2 hours after PCI, or standard care alone. The primary endpoint was infarct size as a percentage of the left ventricle at 30 days, measured on positron emission tomography and magnetic resonance imaging.

Among 148 patients with evaluable imaging, mean infarct size was 23.3% with roxadustat and 22.0% with control (mean difference, 1.3 percentage points; 95% CI, −2.7 to 5.3; P = 0.51), a result confirmed in sensitivity analyses using multiple imputation. Major adverse cardiovascular events occurred in 3.8% and 8.9% of patients, respectively, through 12 months (hazard ratio, 0.42; 95% CI, 0.11-1.63).

In secondary analyses not adjusted for multiplicity, left ventricular ejection fraction increased more with roxadustat than with control at 12 months (3.4% vs 0.5%; adjusted difference, 2.9 percentage points; 95% CI, 0.4-5.3). Left ventricular end-diastolic volume index increased less with roxadustat (1.2 vs 5.7 mL/m²; adjusted difference, −4.5 mL/m²; 95% CI, −8.9 to −0.1), while left ventricular end-systolic volume index did not differ. Prespecified safety endpoints did not differ between groups. Bleeding was reported in 7.6% of roxadustat-treated patients vs 3.8% of controls, a numerical difference the authors said warrants monitoring in future trials.

The authors suggested the neutral primary result may reflect timing, because oral dosing after PCI likely missed the window for limiting reperfusion injury. They cited the modest sample size and open-label design as limitations. They said the secondary ventricular findings were exploratory and require confirmation in adequately powered, blinded trials.

Source: Quan W, Wang Y, Zhang M, et al. Roxadustat treatment after PCI among patients with ST-segment elevation myocardial infarction: a randomized clinical trial. JAMA Netw Open. 2026;9(10):e2637953. doi:10.1001/jamanetworkopen.2026.37953