NEW YORK (Reuters Health) – Among MI patients who have undergone successful revascularization, prompt administration of erythropoietin does not reduce ultimate infarct size. In fact, it may have the opposite effect in elderly patients, according to the findings of a multicenter trial reported in JAMA for May 11.

Preclinical studies with experiment models of MI indicated that erythropoietin reduced infarct size and improved left ventricular function, the authors explain. This led to a phase 2 randomized clinical trial examining the safety and efficacy of erythropoietin versus saline placebo in patients with ST-segment elevation MI (STEMI), administered within 4 hours of reperfusion following primary or rescue PCI.

The study consisted of a dose-escalation phase and an efficacy phase, explain Dr. Samer S. Najjar, with the National Institute on Aging in Baltimore, Maryland, and colleagues.

In the dose-escalation phase, 92 patients were randomized to receive 15,000, 30,000, or 60,000 U epoetin alfa or placebo. The highest dose was deemed acceptable by the monitoring board and was used in the efficacy phase, in which another 131 patients were randomized to receive the study medication or placebo.

At 2-6 days after treatment, infarct size (expressed as a percentage of left ventricular mass) on cardiac magnetic resonance imaging was 15.8% in the epoetin alfa group vs 15.0% in the placebo group (p=0.67), the investigators found.

At 12 weeks, corresponding infarct sizes were 10.6% vs 10.4%, according to the report.

Among patients aged 70 or older, however, mean infarct size on the first assessment was 19.9% in the epoetin group and 11.7% in the placebo group (p=0.03) Similarly, at the 12 week assessment, it was 15.0% vs 9.0%, respectively, although this difference was not significant at a p value of 0.12.

In the safety analysis, death, Mi, stroke, or stent thrombosis occurred in five patients given epoetin but no such events occurred in those receiving placebo, Dr. Najjar and colleagues report.

They conclude, “A single bolus of 60 000 U of epoetin alfa in patients with STEMI within 4 hours following successful PCI did not reduce infarct size and was associated with higher rates of adverse cardiovascular events. Subgroup analyses in our study raised concerns about an increase in infarct size among the small number of patients who were aged 70 years or older.”

In a related editorial, Dr. Deepak L. Bhatt, with Brigham and Women’s Hospital and Harvard Medical School, Boston, Massachusetts, comments: “This finding seems to settle the debate about whether there is a therapeutic role for erythropoietin administration during primary PCI and is a useful negative finding.”

JAMA 2011;305:1863-1811355,1908-1909.