Are There Any Cardioprotective Effects or Safety Concerns of Erythropoietin in Patients With Myocardial Infarction? A Systematic Review

Abstract

Myocardial infarction (MI) is a global cause of morbidity and mortality. MI is the outcome of a chronic process termed atherosclerosis, a buildup of fatty and other substances called plaques inside the coronary vessels, causing hardening and thickening of the arterial wall. Erythropoietin (EPO) is a pleiotropic cytokine released mainly by the kidneys in adults. Besides its well-known erythropoietic functions, EPO possesses anti-apoptotic, mitogenic, and angiogenic effects. This review aims to analyze the strength of any therapeutic or protective value of EPO on the heart and safety concerns regarding its administration in MI individuals. This systematic review was performed based on Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines. Four databases (PubMed, PubMed Central, Google Scholar, and Sciences Direct) were employed to search for articles published in the last 10 years. Focused studies were relevant articles in the English language, trials, reviews, meta-analyses, and studies with a control group. Following the quality assessment process, nine studies were eligible and hence were included in the review consisting of six randomized controlled trials and three systematic reviews and meta-analyses. Contrary to preclinical studies, EPO administration did not significantly have notable effects on mortality, major adverse cardiovascular events, or infarction size reduction. Significant left ventricle ejection fraction amelioration was not appreciated either. However, EPO seems to reduce the incidence of post-MI arrhythmias.

Keywords: coronary heart disease; erythropoietin; erythropoietin effects; myocardial infarction; stemi.

Figure 1. PRISMA 2020 flowchart of the databases and studies

PRISMA, Preferred Reporting Items for Systematic Reviews and Meta-Analyses [14]

Figure 2. Signaling pathways targeted by EPO-EPOR binding

Figure created by the author, Jean-Baptiste, using Mind the Graph. Bad, BCL2-associated agonist of cell death; Bcl-xL, B-cell lymphoma-extra large; GSK3, glycogen synthase kinase 3; JAK 2, Janus kinase 2; MAPK, mitogen-activated protein kinase; PI3K, phosphoinositide 3-kinases; PKC, protein kinase C; STAT5, signal transducer and activator of transcription

Figure 3. EPO’s effects on the cardiovascular system

Figure created by the author, Jean-Baptiste, using Mind the Graph EPCs, endothelial progenitor cells; ET-1, endothelin 1; NE, norepinephrine; NOS, nitric oxide synthase; PAI, plasminogen activator inhibitor 1; VEGF, vascular endothelial growth factor