HEBE III: A prospective, randomised, clinical study to examine the effects of a single bolus erythropoietin on left ventricular function in patients with an acute myocardial infarction

Erythropoetin (EPO) is commonly known as an effective treatment for anemia,
(partly) caused by an inadequate production of endogenous EPO (e.g., renal
failure). However, we and others suggested several important
extra-hematopoeitic effects of EPO, which might be beneficial in the setting of
an acute myocardial infarction. Recent animal studies provided very consistent
evidence for a reduced infarct size and improved left ventricular function
caused by EPO administration. In addition, we and others have mainly explained
the beneficial effects of EPO by non-hematopoietic effects, such as reduction
of apoptosis and stimulation of neovascularisation.
Clinical studies with EPO in non-anemic patients are scarce. Ehrenreich et al
recently conducted an efficacy and safety study of recombinant human
Erythropoietin (rh-EPO) therapy in men suffering from stroke. They found that
high dose of EPO administered the first three days after stroke (total dose
100.000 IU), was well tolerated and associated with a marked reduction in
cerebral infarct size, and an improvement in clinical outcome. We performed a
safety study in our department on the effects of a single bolus of EPO (60.000
IU) in patients with an acute myocardial infarction. Serum EPO levels increased
a 200-fold, but no significant effects on hematopoiesis were seen. In addition,
EPO administration was not associated with hypertension, nor with an increase
in thrombocytes or thrombotic events.
In conclusion, experimental data clearly showed that a single bolus of EPO
after the onset of an acute myocardial infarction reduced myocardial infarct
size, and improved left ventricular function. In our safety study, EPO
administration in patients with an acute myocardial infarction was safe and
well tolerated.

The primary objective of this study is to establish the effects of a single
bolus EPO administered just before a primary PCI for a first acute myocardial
infarction, on left ventricular ejection fraction after 6 weeks, measured with
planar radionuclide ventriculography.
The secondary objective of this study is to establish the effects of a single
bolus EPO on safety, myocardial infarct size, and cardiovascular events in
patients after a first acute myocardial infarction.

Prospective, Randomised, Open label study with Blinded Endpoint analysis
(PROBE).

In one group one bolus of EPO (Eprex, about 60.000 IU) will be administered
intravenously in 30 minutes, within 3 hours after the primary PCI procedure
and the other group will receive standard therapy.

Blood will be sampled 7 times during the whole study period of 6 weeks
according to routine clinical practice. Planar radionuclide ventriculography
will be performed at 6 weeks follow up. A previous safety study showed no
adverse events after administration of EPO. Therefore, we expect that the risks
are negligible and do not expand the possible benefits.