Myocardial Infarction: Cardioprotection by Erythropoietin - Tissue-Protective Cytokines: Methods and Protocols - page 280

The only clinical trial in the USA was recently completed ( 64, 65 ).
It was randomized, double-blind, placebo-controlled, multicenter
phase I-II trial evaluating the effect of epoietin-alpha in the patients
with large MI. In the dose escalating safety phase the dose of EPO
was tested in the cohorts receiving 15,000, 30,000, and 60,000 IU.
In the phase II, 65 patients received EPO within 4 h of PCI (within
8 h of symptom onset). Equal number of patients received placebo
at that time. Main outcome was an MI size estimated as a percent
of LV mass measured by cardiac magnetic resonance imaging 2-6
days after treatment and 12 weeks later. MI size was not reduced
by EPO measured either during the first CMR, or 12 weeks later.
There was a tendency of increased MI size and the number of
adverse effect in older patients.
A small clinical trial, which authors considered a pilot, com-
pleted recently in Italy ( 66 ) was the only one so far with encourag-
ing outcome. It was a single-center, randomized, placebo controlled,
double-blind study. Thirty patients with a first ST-segment eleva-
tion AMI underwent PCI within 6 h of symptoms onset. EPO,
33,000 IU (type is not reported) or placebo were delivered intrave-
nously in 50 mL of saline over 30 min, starting before and contin-
ued during PCI. This dose was repeated 24 and 48 h after PCI. MI
size was estimated enzymatically. Echocardiography and cardiac
magnetic resonance studies were performed shortly after admission
and repeated after 6 months. Seventy-two hours after initiation of
treatment the level of CD34+ cells was reported four times higher
in the EPO group compared with placebo group ( p = 0.002).
Enzymatically measured MI was smaller ( p <0.03) in the EPO
group. LVEF measured by CMR improved after 6 months in the
EPO group vs. placebo. EF measured by echocardiography was not
different at 6 months between groups, but in the EPO group EDV
did not change and ESV was smaller, while in placebo group these
changes were reversed.
Finally, a clinical trial, EPAMINONDAS (Exogenous erythro-
poietin in Acute Myocardial Infarction New Outlook aNd Dose),
is underway in Italy ( 67 ). The results are not available at this time.
It is a multicenter, randomized controlled trial that enrolls >100
patients with ST-segment elevation MI. Two doses of epoetin-alfa
will be tested (100 and 200 IU/kg). EPO treatment (or placebo)
will be repeated in the first 3 days after primary PCI with the first
dose given within 12 h of procedure. Primary end-points will be an
enzymatically measured MI size and results of cardiac MRI.
Secondary end-points will be 12-month cardiac remodeling and
safety events.
Therefore, all completed clinical trials except one ( 66 ) failed to
demonstrate any or almost any beneficial effects of EPO treatment
in the setting of acute stage of MI. All these trials have one com-
mon trait—timing of application of experimental drug is different
from that used in the experiment on animals. Experimental data