Update on Phase II Studies of Erythropoietin in Acute Myocardial Infarction. Rationale and Design of Exogenous ErythroPoietin in Acute Myocardial Infarction: New Outlook ANd Dose Association Study (EPAMINONDAS)

Overview

Journal J Thromb Thrombolysis

Specialty Cardiology & Vascular Diseases

Date 2009 Jun 18

PMID 19533304

Citations 9

Authors

Felicita Andreotti

Luciano Agati

Elena Conti

Eleonora Santucci

Teresa Rio

Federica Tarantino

Luigi Natale

Daniele Berardi

Antonella Mattatelli

Beatrice Musumeci

Lorenzo Bonomo

Massimo Volpe

Filippo Crea

Camillo Autore

Affiliations

Soon will be listed here.

Abstract

Erythropoietin (Epo) is a hematopoietic hormone produced mainly by the kidneys in response to hypoxia. Recent acquisitions in the fields of hematology, neurology, cardiology, and experimental medicine show cytoprotective, angiogenetic and antiinflammatory effects of Epo. Exogenous erythroPoietin in Acute Myocardial Infarction: New Outlook aNd Dose Association Study (EPAMINONDAS, EudraCTno. 200500485386) is one of four ongoing randomized controlled trials, each testing the effects of Epo in >or=100 patients with STEMI. EPAMINONDAS is a multicenter, prospective, double-blind, placebo-controlled, dose-finding study assessing intravenous moderate doses of human recombinant Epo (epoietin-alpha, 100 or 200 IU/kg/die) versus placebo, given on the first 3 days, in 102 patients with first ST-segment elevation myocardial infarction. Initial dosing is within 12 h of primary percutaneous coronary revascularization. The primary endpoint is infarct size, quantified by CK-MB time-concentration curve, left ventricular wall motion score index, and pattern of contrast-enhanced magnetic resonance imaging. Secondary endpoints are ischemic recurrences, ventricular remodelling, and safety events, assessed in-hospital and at 12 months' follow-up. The results of current phase II studies will help define the safety/efficacy profile of Epo for patients with STEMI.

Citing Articles

Safety of off-label erythropoiesis stimulating agents in critically ill patients: a meta-analysis.

Mesgarpour B, Heidinger B, Schwameis M, Kienbacher C, Walsh C, Schmitz S Intensive Care Med. 2013; 39(11):1896-908.

PMID: 23928897 DOI: 10.1007/s00134-013-3030-9.

Myocardial infarction: cardioprotection by erythropoietin.

Talan M, Latini R Methods Mol Biol. 2013; 982:265-302.

PMID: 23456875 PMC: 6207951. DOI: 10.1007/978-1-62703-308-4_17.

Serum EPO and VEGF levels in patients with sleep-disordered breathing and acute myocardial infarction.

Kukwa W, Glowczynska R, Filipiak K, Kukwa A, Opolski G, Budaj-Fidecka A Sleep Breath. 2013; 17(3):1063-9.

PMID: 23340852 PMC: 3742958. DOI: 10.1007/s11325-013-0801-z.

Clinical use of erythropoietin in chronic kidney disease: outcomes and future prospects.

Provatopoulou S, Ziroyiannis P Hippokratia. 2011; 15(2):109-15.

PMID: 22110290 PMC: 3208971.

Pharmacologic and genetic strategies to enhance cell therapy for cardiac regeneration.

Kanashiro-Takeuchi R, Schulman I, Hare J J Mol Cell Cardiol. 2011; 51(4):619-25.

PMID: 21645519 PMC: 3408226. DOI: 10.1016/j.yjmcc.2011.05.015.

References

Biagini E, van Geuns R, Baks T, Boersma E, Rizzello V, Galema T . Comparison between contrast echocardiography and magnetic resonance imaging to predict improvement of myocardial function after primary coronary intervention. Am J Cardiol. 2006; 97(3):361-6. DOI: 10.1016/j.amjcard.2005.08.053. View

Riksen N, Hausenloy D, Yellon D . Erythropoietin: ready for prime-time cardioprotection. Trends Pharmacol Sci. 2008; 29(5):258-67. DOI: 10.1016/j.tips.2008.02.002. View

Calvillo L, Latini R, Kajstura J, Leri A, Anversa P, Ghezzi P . Recombinant human erythropoietin protects the myocardium from ischemia-reperfusion injury and promotes beneficial remodeling. Proc Natl Acad Sci U S A. 2003; 100(8):4802-6. PMC: 153636. DOI: 10.1073/pnas.0630444100. View

Marzo F, Lavorgna A, Coluzzi G, Santucci E, Tarantino F, Rio T . Erythropoietin in heart and vessels: focus on transcription and signalling pathways. J Thromb Thrombolysis. 2008; 26(3):183-7. DOI: 10.1007/s11239-008-0212-3. View

Lipsic E, van der Meer P, Voors A, Westenbrink B, van den Heuvel A, de Boer H . A single bolus of a long-acting erythropoietin analogue darbepoetin alfa in patients with acute myocardial infarction: a randomized feasibility and safety study. Cardiovasc Drugs Ther. 2006; 20(2):135-41. DOI: 10.1007/s10557-006-7680-5. View

Maiese K, Li F, Chong Z . New avenues of exploration for erythropoietin. JAMA. 2005; 293(1):90-5. PMC: 2254180. DOI: 10.1001/jama.293.1.90. View

Takemura G, Nakagawa M, Kanamori H, Minatoguchi S, Fujiwara H . Benefits of reperfusion beyond infarct size limitation. Cardiovasc Res. 2009; 83(2):269-76. DOI: 10.1093/cvr/cvp032. View

Heeschen C, Aicher A, Lehmann R, Fichtlscherer S, Vasa M, Urbich C . Erythropoietin is a potent physiologic stimulus for endothelial progenitor cell mobilization. Blood. 2003; 102(4):1340-6. DOI: 10.1182/blood-2003-01-0223. View

Bogoyevitch M . An update on the cardiac effects of erythropoietin cardioprotection by erythropoietin and the lessons learnt from studies in neuroprotection. Cardiovasc Res. 2004; 63(2):208-16. DOI: 10.1016/j.cardiores.2004.03.017. View

10.

Fox K, Steg P, Eagle K, Goodman S, Anderson Jr F, Granger C . Decline in rates of death and heart failure in acute coronary syndromes, 1999-2006. JAMA. 2007; 297(17):1892-900. DOI: 10.1001/jama.297.17.1892. View

11.

Van de Werf F, Bax J, Betriu A, Blomstrom-Lundqvist C, Crea F, Falk V . Management of acute myocardial infarction in patients presenting with persistent ST-segment elevation: the Task Force on the Management of ST-Segment Elevation Acute Myocardial Infarction of the European Society of Cardiology. Eur Heart J. 2008; 29(23):2909-45. DOI: 10.1093/eurheartj/ehn416. View

12.

Corwin H, Gettinger A, Fabian T, May A, Pearl R, Heard S . Efficacy and safety of epoetin alfa in critically ill patients. N Engl J Med. 2007; 357(10):965-76. DOI: 10.1056/NEJMoa071533. View

13.

Besarab A, Bolton W, Browne J, Egrie J, Nissenson A, Okamoto D . The effects of normal as compared with low hematocrit values in patients with cardiac disease who are receiving hemodialysis and epoetin. N Engl J Med. 1998; 339(9):584-90. DOI: 10.1056/NEJM199808273390903. View

14.

Bohlius J, Langensiepen S, Schwarzer G, Seidenfeld J, Piper M, Bennett C . Recombinant human erythropoietin and overall survival in cancer patients: results of a comprehensive meta-analysis. J Natl Cancer Inst. 2005; 97(7):489-98. DOI: 10.1093/jnci/dji087. View

15.

Conti E, Carrozza C, Capoluongo E, Volpe M, Crea F, Zuppi C . Insulin-like growth factor-1 as a vascular protective factor. Circulation. 2004; 110(15):2260-5. DOI: 10.1161/01.CIR.0000144309.87183.FB. View

16.

Moon C, Krawczyk M, Paik D, Lakatta E, Talan M . Cardioprotection by recombinant human erythropoietin following acute experimental myocardial infarction: dose response and therapeutic window. Cardiovasc Drugs Ther. 2005; 19(4):243-50. DOI: 10.1007/s10557-005-3189-6. View

17.

Moon C, Krawczyk M, Ahn D, Ahmet I, Paik D, Lakatta E . Erythropoietin reduces myocardial infarction and left ventricular functional decline after coronary artery ligation in rats. Proc Natl Acad Sci U S A. 2003; 100(20):11612-7. PMC: 208806. DOI: 10.1073/pnas.1930406100. View

18.

Wakeen M, Zimmerman S . Association between human recombinant EPO and peripheral vascular disease in diabetic patients receiving peritoneal dialysis. Am J Kidney Dis. 1998; 32(3):488-93. DOI: 10.1053/ajkd.1998.v32.pm9740167. View

19.

Fandrey J . Oxygen-dependent and tissue-specific regulation of erythropoietin gene expression. Am J Physiol Regul Integr Comp Physiol. 2004; 286(6):R977-88. DOI: 10.1152/ajpregu.00577.2003. View

20.

Belonje A, Voors A, van Gilst W, Anker S, Slart R, Tio R . Effects of erythropoietin after an acute myocardial infarction: rationale and study design of a prospective, randomized, clinical trial (HEBE III). Am Heart J. 2008; 155(5):817-22. DOI: 10.1016/j.ahj.2007.12.036. View