Roxadustat fails to reduce heart-attack damage in randomized trial

Roxadustat did not significantly reduce the extent of heart-muscle damage when given after emergency coronary intervention, according to randomized trial results published October 9 in JAMA Network Open. The finding limits the evidence for repurposing the anemia medicine to protect the heart after a major heart attack.

The clinical question matters for healthy aging: surviving an acute cardiovascular event is only part of the challenge. Preserving the capacity to remain active afterward is another. A drug intended to protect injured tissue needs evidence that its biological effects translate into meaningful recovery.

What the trial measured

ROXAMI was a single-center, open-label phase 2 trial in Shanghai. It randomized 158 adults with ST-segment elevation myocardial infarction to roxadustat or standard care. Enrollment ran from April 2021 through March 2024; average age was approximately 64, and 84% were men.

The primary analysis included 148 participants with evaluable imaging. At 30 days, damaged tissue averaged 23.3% of the left ventricle with roxadustat versus 22.0% with control. The difference was 1.3 percentage points, with a 95% confidence interval from −2.7 to 5.3.

Selected secondary measures of ventricular function and remodeling favored treatment at one year, but the analyses lacked adjustment for multiple comparisons. They remain exploratory. The single-center design, predominantly male population and missing imaging also limit interpretation.

An established medicine, a different clinical question

Roxadustat is the active ingredient in Evrenzo, which received European Union authorization in August 2021 for symptomatic anemia associated with chronic kidney disease in adults. That authorization addresses a different condition from the heart-attack setting examined here.

The European Medicines Agency explains that roxadustat acts on an enzyme involved in the body's response to low oxygen. Its effects include stimulating production of erythropoietin and hemoglobin, supporting red-blood-cell production and oxygen transport. The established clinical evidence concerns correcting anemia; it cannot automatically establish protection of heart muscle.

The regulator also lists risks including high blood pressure and blood clots. Those established safety considerations help explain why repurposing requires its own assessment of benefits and harms. Prior authorization supplies useful knowledge about a medicine, but it does not settle whether a new patient population will benefit.

Why tissue protection matters

The National Heart, Lung, and Blood Institute describes a heart attack as a sudden interruption of oxygen-bearing blood flow to part of the heart muscle. Without prompt restoration of that flow, muscle begins to die. The longer oxygen deprivation lasts, the greater the damage can become.

Many survivors subsequently lead active lives, the institute notes. That makes preservation of function a relevant healthspan goal, while also underscoring the distinction between a laboratory or imaging measurement and a person's eventual recovery.

For interpreting trials, a primary endpoint provides the central test of the treatment hypothesis. Examining numerous additional outcomes creates more opportunities for apparently favorable differences to emerge by chance. Such findings can help formulate another study, but should carry less weight than a successful prespecified primary comparison.

The practical reading of ROXAMI is therefore restrained: the tested strategy has not established the intended tissue-protection benefit. Any further claim about improved recovery would need a study designed to confirm that outcome, with sufficient follow-up and a clear assessment of safety.