A single bolus of erythropoietin does not improve cardiac function after an acute myocardial infarction: results from the HEBE III trial

Results from the HEBE III study, a prospective, randomised, multicentre trial performed in seven centres in the Netherlands, suggest that the promising effects of erythropoieitin seen in previous smaller studies cannot be confirmed for the improvement of clinical outcome in patients with a first ST-elevation myocardial infarction.
MI remains a major hazard for millions of patients in Europe. Despite improvements in treatment, the majority still end up with reduced cardiac function, and strategies to improve post-MI cardiac function are strongly needed. One approach, suggested in experimental and smaller clinical studies, is the administration of erythropoietin (EPO), currently used for the treatment of anemia caused by renal disease. The HEBE III study was designed to study the effects of a single intravenous bolus of EPO on clinical outcome in patients with a first ST-elevation MI. The primary endpoint of the trial - as a measure of cardiac function - was left ventricular ejection fraction (LVEF) after six weeks, with secondary endpoints assessed according to infarct size and major adverse cardiovascular events (MACE).
The trial was conducted in 529 randomised STEMI patients and headline results showed that this single IV bolus of EPO did not improve cardiac function. However, patients who received EPO had fewer major cardiac events, such as heart failure, compared with the control group.
The HEBE III trial studied the effect of a single bolus of 60,000 IU epoetin alfa on LVEF. EPO was administered intravenously within three hours after a successful PCI for a first STEMI. The study aimed to find a 3% increase of LVEF in patients treated with EPO compared to standard care. In total, 529 patients were included in the study, in which 263 patients were assigned to the EPO group and 266 to the control group. After six weeks, LVEF was 53% in the EPO group and 52% in the control group, but this 1% difference was too small to be statistically or clinically significant. Furthermore, infarct size, measured by proteins in the blood, was also not significantly different between the two groups. However, in the EPO group, only eight patients suffered a major cardiac adverse event, compared to 19 in the control group.
Commenting on the results, principal investigator Dr Adriaan Voors from the University Medical Center, Groningen, the Netherlands, said: "The promising effects of erythropoieitin in previous smaller studies could not be confirmed in this large clinical trial. The reduction of major cardiac effects is of interest, but, since the study was not primarily designed to reduce cardiac effects, and the numbers are small, we should be careful with its interpretation. Larger clinical trials powered to detect a reduction in hard clinical endpoints should be performed before EPO can be routinely used in patients with an acute heart attack."