High-dose erythropoietin in patients with acute myocardial infarction: A pilot, randomised, placebo-controlled study

Ferrario, Maurizio; Arbustini, Eloisa; Massa, Margherita; Rosti, Vittorio; Marziliano, Nicola; Raineri, Claudia; Campanelli, Rita; Bertoletti, Alessandra; Ferrari, Gaetano M. De; Klersy, Catherine; L, Angoli; Bramucci, Ezio; Marinoni, Barbara; Ferlini, Marco; Moretti, Enza; Raisaro, A; Repetto, Alessandra; Schwartz, Peter J.; Tavazzi, Luigi

doi:10.1016/j.ijcard.2009.10.028

Cited by 72 publications

(54 citation statements)

References 51 publications

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“…13 Similarly, Liem et al, who treated a subset of patients with non-ST-segment elevation acute coronary syndromes with a single bolus of recombinant α-EPO, did not report any beneficial clinical effects or changes in the release of cardiac enzymes. 14 Our present finding is well consistent with the clinical data by Ferrario et al, 12 while the discrepancies might be explained by the differences in the drugs, treatment strategies and patient settings. Although the 3 previous studies aimed to examine the safety and cardiac effect of high-dose EPO treatment on LV remodeling, the anti-restenosis action of EPO has not yet been studied.…”

Section: Discussionsupporting

confidence: 91%

“…Ferrario et al also reported that EPO is associated with a significant overexpression of the pro-angiogenic genes and anti-apoptotic Akt and NF-κB genes in peripheral blood cells from AMI patients. 12 In contrast, Janmaat et al reported that EPO accelerated smooth muscle cell-rich neointimal formation in carotid artery ligation model of mice through endothelial cell activation involving enhanced PDGF-BB release, 28 in which endothelial cells were not injured unlike our balloon-injured artery model. 19 Thus, the condition of resident endothelial cells might affect the EPO-mediated vascular effect.…”

Section: Discussionmentioning

confidence: 57%

“…Ferrario et al reported the first clinical study documenting that short-term high-dose EPO in the early phase of PCI-treated AMI improves LV function and decreases infarct size, in which hemoglobin values remained within normal ranges. 12 Lipsic et al did not observe any significant change in echocardiographic or enzymatic indexes after a single high-dose bolus of the EPO analogue darbepoietin. 13 Similarly, Liem et al, who treated a subset of patients with non-ST-segment elevation acute coronary syndromes with a single bolus of recombinant α-EPO, did not report any beneficial clinical effects or changes in the release of cardiac enzymes.…”

Section: Discussionmentioning

confidence: 92%

“…In the recent clinical pilot studies in patients with AMI treated with PCI, Ferrario et al 12 reported that short-term high-dose EPO administration induces an improvement in cardiac function and a decrease in infarct size without thrombotic complications, whereas Lipsic et al 13 did not observe any significant change in echocardiographic or enzymatic indexes after a single high-dose bolus of EPO analogue darbepoietin. Similarly, Liem et al reported no beneficial clinical effects in the release of cardiac enzymes after a single high-dose bolus of recombinant α-EPO in patients with acute coronary syndrome.…”

mentioning

confidence: 99%

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Erythropoietin Prevention Trial of Coronary Restenosis and Cardiac Remodeling After ST-Elevated Acute Myocardial Infarction (EPOC-AMI) - A Pilot, Randomized, Placebo-Controlled Study -

Taniguchi¹,

Nakamura

Sawada

et al. 2010

Circ J

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Circulation Journal Official Journal of the Japanese Circulation Society http://www. j-circ.or.jp arly primary percutaneous coronary intervention (PCI) gives the higher rate of recanalization, contributing to decrease in prevalence of cardiac events and improvement of left ventricular (LV) contractility and survival prognosis. 1-3 Although additional therapies have been reported for cardioprotection after acute myocardial infarction (AMI), 4-6 LV remodeling after AMI is complicated by cardiac failure accompanying enlargement of LV chamber to worsen long-term prognosis. 7, 8 We have often noticed that patients with AMI develops remarkable LV remodeling in the chronic phase in spite of the early recanalization by PCI. Editorial p 2290Erythropoietin (EPO), which controls erythropoiesis, is a glycoprotein hormone with a molecular weight of 34,000 consisting of 165 amino acid residues, and is secreted from the kidney in response to hypoxic stimuli. 9 EPO is expressed by hypoxic-ischemic vascular endothelial cells and myocytes, 10 whose EPO receptors make them potential targets of EPO-mediated endocrine and autocrine/paracrine actions, such as anti-apoptosis and pro-angiogenic properties, resulting in the observation that high-dose EPO reduces infarct size and preserves ventricular function in animal models of reper-

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Section: Discussionsupporting

confidence: 91%

Section: Discussionmentioning

confidence: 57%

Section: Discussionmentioning

confidence: 92%

mentioning

confidence: 99%

See 2 more Smart Citations

Erythropoietin Prevention Trial of Coronary Restenosis and Cardiac Remodeling After ST-Elevated Acute Myocardial Infarction (EPOC-AMI) - A Pilot, Randomized, Placebo-Controlled Study -

Taniguchi¹,

Nakamura

Sawada

et al. 2010

Circ J

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“…A second small study by Ferrario et al 61 showed benefits of erythropoietin in the setting of acute MI. This was a singlecenter study of 30 patients with a first uncomplicated MI undergoing PCI who were randomized to erythropoietin (33×10 3 IU) before PCI, and then 24 and 48 hours after admission versus placebo.…”

Section: Other Older and Newer Pharmacological Approaches Erythropoietinmentioning

confidence: 98%

Current State of Clinical Translation of Cardioprotective Agents for Acute Myocardial Infarction

Kloner

2013

Circulation Research

138

112

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Abstract:There is continued interest in the concept of limiting myocardial infarct size with adjunctive agents administered along with reperfusion injury; however, there remains considerable controversy in the literature. The purpose of this article is to review the medical literature on clinical trials performed during the past 3 years that have attempted to reduce myocardial infarct size by administration of adjunctive therapies along with reperfusion therapy. A PubMed-driven literature search revealed a host of clinical trials focusing on the following prominent types of therapies: endogenous conditioning (postconditioning and remote ischemic conditioning); rapid cooling; pharmacological therapy (cyclosporine, abciximab, clopidogrel, tirofiban, erythropoietin, thrombus aspiration, adenosine, glucose-insulin-potassium, statins, antidiabetic agents, FX06, iron chelation, and ranolazine). Although there remains some controversy, quite a few of these studies showed that adjunctive therapy further reduced myocardial infarct size when coupled with reperfusion. Antiplatelet agents are emerging as some of the newest agents that seem to have cardioprotective capabilities. Postconditioning has become a bit more controversial in the clinical literature; remote conditioning, early and rapid cooling, adenosine, and ranolazine are intriguing therapies deserving of larger studies. Certain agents and maneuvers, such as erythropoietin, protein kinase C δ inhibitors, iron chelation, and intra-aortic balloon counterpulsation, perhaps should be retired. The correct adjunctive therapy administered along with reperfusion has the capability of further reducing myocardial injury during ST-segment-elevation myocardial infarction. ( infarct size reducing agents in clinical trials. Some of these disappointing agents included antibodies that prevent white blood cell adhesion to the endothelium; eniporide, a sodium/hydrogen exchange inhibitor; caldaret, an intracellular calcium-handling modulator; nicorandil, a potassium ATP channel opener/vasodilator; glucose-insulin-potassium (GIK); delcasertib (a protein kinase C δ inhibitor); and erythropoietin. 5 However, some agents and maneuvers that were observed to work in experimental models did show promise in clinical trials of MI under the right circumstances: postconditioning; remote conditioning; cyclosporine (maintains the mitochondrial permeability transition pore closed); intravenous adenosine infusions; atrial natriuretic peptide; mild hypothermia induced before reperfusion; supersaturated oxygen therapy and others. [4][5][6][7] The reasons for discrepancies between experimental findings and clinical trials have been reviewed in detail. 6,7 Since these reviews were written there have been a large number of new clinical trials recently published during the past 3 years, on the basis of literature searches through PubMed. These trials cover additional new studies on therapies, such as conditioning, abciximab, clopidogrel, erythropoietin, hypothermia, thrombectomy, intracoronary adenosine...

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Intravenous Erythropoietin in Patients With ST-Segment Elevation Myocardial Infarction

Najjar

Rao

Melloni

et al. 2011

JAMA

206

140

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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.

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High-dose erythropoietin in patients with acute myocardial infarction: A pilot, randomised, placebo-controlled study

Cited by 72 publications

References 51 publications

Erythropoietin Prevention Trial of Coronary Restenosis and Cardiac Remodeling After ST-Elevated Acute Myocardial Infarction (EPOC-AMI) - A Pilot, Randomized, Placebo-Controlled Study -

Erythropoietin Prevention Trial of Coronary Restenosis and Cardiac Remodeling After ST-Elevated Acute Myocardial Infarction (EPOC-AMI) - A Pilot, Randomized, Placebo-Controlled Study -

Current State of Clinical Translation of Cardioprotective Agents for Acute Myocardial Infarction

Intravenous Erythropoietin in Patients With ST-Segment Elevation Myocardial Infarction

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