EPO shows no benefit as PCI adjunct in STEMI
MedWire News: High-dose erythropoietin (EPO) has no effect on myocardial infarct (MI) size when administered as an adjunct to primary percutaneous coronary intervention (PCI) and may even be detrimental, results of a randomized controlled trial show.
It represents the latest in a line of "discordant findings between preclinical animal studies and the clinical translation of novel cardioprotective strategies," note co-author Derek Yellon (University College London, UK) and colleagues, who caution against further human studies.
Despite recent advances in PPCI, the morbidity and mortality of ST-elevation myocardial infarction (STEMI) patients remain significant.
This may be due, in part, to the presence of myocardial reperfusion injury, a phenomenon which induces further cardiomyocyte death.
"Therefore, novel cardioprotective agents capable of reducing lethal myocardial reperfusion injury are required to limit myocardial infarct (MI) size, preserve cardiac function and improve clinical outcomes," Yellon et al explain in the journal Heart.
One such potential agent, EPO, appears to exert pleiotropic effects beyond that of hematopoiesis, which include both neuroprotection and cardioprotection. Indeed, acute administration of high-dose EPO at the time of reperfusion has been reported in animal models to reduce MI size by approximately 50%.
To test whether this translates into the human setting, the researchers performed a double-blinded, randomized, placebo-controlled trial in 51 STEMI patients undergoing primary PCI.
Patients were randomly assigned to receive either a single intravenous bolus of EPO (50,000 IU) prior to PCI with a further bolus given 24 hours later (n=26) or placebo (n=25).
The size of MI was measured by calculating 24-hour area under the curve of troponin T and with cardiac magnetic resonance imaging (CMR) on day 2 and at 4 months.
Yellon et al report that EPO treatment failed to reduce MI size with a troponin T area under the curve of 114.7 mg/ml for EPO versus 100.9 mg/ml for placebo and infarct mass by CMR of 33,616 g for EPO vs 25,616 g for placebo.
Unexpectedly, EPO treatment doubled the incidence of microvascular obstruction (82% EPO vs 47% placebo) and significantly increased indexed left ventricular (LV) end-diastolic volumes (84,610 ml/m2 EPO vs 73,613 ml/m2 placebo). At 4 months, there were no significant differences between groups.
The researchers suggest that the discordance between clinical and pre-clinical trials could be explained by proinflammatory and prothrombotic states associated with an MI in middle-aged patients with comorbidities such as diabetes, dyslipidemia, and hypertension. These are not easily reproduced by experimental coronary artery occlusion in disease-free juvenile small-to-medium-size animal models.
They say further work should try and elucidate the protective pathways of EPO in the preclinical setting in an effort to find EPO analogues which may provide protective benefits without the apparent associated side effects.
By Andrew Czyzewski