Intravenous Erythropoietin in Patients With ST-Segment Elevation Myocardial Infarction

Abstract

Context Acute ST-segment elevation myocardial infarction (STEMI) is a leading cause of morbidity and mortality. In experimental models of MI, erythropoietin reduces infarct size and improves left ventricular (LV) function. Objective To evaluate the safety and efficacy of a single intravenous bolus of epoetin alfa in patients with STEMI. Design, Setting, and Patients Prospective, randomized, double-blind, placebo-controlled trial with a dose-escalation safety phase and a single-dose (60,000 units of epoetin alfa) efficacy phase involving 222 patients with STEMI who underwent successful percutaneous coronary intervention (PCI) as a primary or rescue reperfusion strategy. Intervention Participants were randomly assigned to treatment with intravenous epoetin alfa or matching saline placebo administered within 4 hours of reperfusion. Main Outcome Measure Infarct size, expressed as a percentage of LV mass, assessed by cardiac magnetic resonance (CMR) imaging 2–6 days after study medication administration. Results In the efficacy cohort (n=138), infarct size did not differ between groups at either 2–6 days (15.8±10.3 vs. 15.0±10.0, P=.666) or 12±2 weeks (10.6±8.6 vs. 10.4±7.6, P=.886). Left ventricular ejection fraction also did not differ between groups at either the early (48.2±9.1 vs. 48.9±8.7, P=.671) or late (52.5±9.3 vs. 52.0±8.8, P=.760) timepoints. In pre-specified analyses of patients aged ≥70 years (n=21), mean infarct size within the first week was larger in the epoetin alfa arm than in the placebo group (19.9±9.9 vs.11.7±7.2, P=.026). Patients who received epoetin alfa had a higher incidence of the composite endpoint of death, myocardial infarction, stroke, or stent thrombosis (4.0% vs. 0.0%, P=.042), and a higher incidence of serious adverse events (20.0% vs. 10.3%, P=.052). Conclusions In STEMI patients successfully reperfused with primary or rescue PCI, a single intravenous bolus of epoetin alfa did not reduce infarct size and was associated with higher rates of adverse cardiovascular events. Furthermore, it may be associated with increased infarct size in older patients. Trial Registration clinicaltrials.gov identifier NCT00378352.

Autologous Mesenchymal Stem Cells Mobilize cKit + and CD133 + Bone Marrow Progenitor Cells and Improve Regional Function in Hibernating Myocardium

“…For example, in a recent large clinical trial, average ejection fraction in unselected patients after first ST-elevation infarction was near normal (Ϸ50%). 61 Scar volume initially averaged only Ϸ15% of the LV and decreased further over the ensuing months because the acute infarct normally contracts. When heart failure develops in ischemic cardiomyopathy, there is diffuse rather than single-vessel coronary artery disease and patchy fibrosis.…”

Acute coronary syndrome with intraventricular thrombus after using erythropoietin

“…Two weeks prior to presentation with stent thrombosis the patient had a 50% dose increase of long term erythropoietin. In patients with STEMI who had successful reperfusion with primary or rescue PCI, a single intravenous bolus of epoetin alpha within 4 hours of PCI did not reduce infarct size and was associated with higher rates of adverse cardiovascular events (8).…”

Low-Dose Erythropoietin in Patients With ST-Segment Elevation Myocardial Infarction (EPO-AMI-II) ― A Randomized Controlled Clinical Trial ―

“…In the REVEAL study, subanalysis showed that high-dose EPO (60,000 IU) was associated with a higher incidence of severe adverse events, although those authors noted that the analysis was based on a very small number of events. 9 In contrast, in the HEBE III study, subanalysis revealed that EPO treatment showed a trend towards a decrease in enzymatic infarct size, and the incidence of the combined endpoint (cardiovascular death, MI, in-stent thrombosis, UAP and HF) was significantly decreased. 10 In the REVIVAL study, EPO (33,000 IU×3) treatment showed a trend towards an increased rate of severe adverse effects.…”