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Intravenous erythropoietin in patients with ST-segment elevation myocardial infarction: REVEAL: a randomized
Samer S Najjar1, Sunil V Rao, Chiara Melloni
1Intramural Research Program, National Institute on Aging, National Institutes of Health, Baltimore, Maryland, USA. Samer.S.Najjar@medstar.net
Insights
Epoetin alfa did not reduce infarct size in ST-segment elevation myocardial infarction (STEMI) patients after reperfusion. The treatment was linked to increased adverse cardiovascular events, particularly in older individuals.
Area of Science:
- Cardiology
- Pharmacology
- Clinical Trials
Background:
- Acute ST-segment elevation myocardial infarction (STEMI) is a significant cause of death and disability.
- Erythropoietin has shown promise in experimental models for reducing infarct size and improving left ventricular function post-myocardial infarction (MI).
Purpose of the Study:
- To assess the safety and efficacy of a single intravenous dose of epoetin alfa in patients experiencing STEMI.
- To determine if epoetin alfa administration impacts infarct size and left ventricular remodeling.
Main Methods:
- A prospective, randomized, double-blind, placebo-controlled trial (REVEAL) involving 222 STEMI patients undergoing percutaneous coronary intervention (PCI).
- Patients received either epoetin alfa (60,000 U) or placebo intravenously within 4 hours of reperfusion.
- Infarct size was measured using cardiac magnetic resonance (CMR) imaging at two time points: early post-intervention and 12 weeks later.
Main Results:
- No significant difference in infarct size was observed between the epoetin alfa and placebo groups at either early or late CMR assessments.
- A prespecified analysis indicated a larger infarct size in patients aged 70 years or older treated with epoetin alfa compared to placebo (P=.03).
- The incidence of composite adverse cardiovascular events (death, MI, stroke, stent thrombosis) was higher in the epoetin alfa group (4.0%) than in the placebo group (0%) (P=.04).
Conclusions:
- A single intravenous bolus of epoetin alfa within 4 hours of reperfusion did not reduce infarct size in STEMI patients.
- The treatment was associated with an increased risk of adverse cardiovascular events.
- Concerns were raised regarding a potential increase in infarct size among older patients treated with epoetin alfa.
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:
A prospective, randomized, double-blind, placebo-controlled trial with a dose-escalation safety phase and a single dose (60,000 U of epoetin alfa) efficacy phase; the Reduction of Infarct Expansion and Ventricular Remodeling With Erythropoietin After Large Myocardial Infarction (REVEAL) trial was conducted at 28 US sites between October 2006 and February 2010, and included 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 percentage of LV mass, assessed by cardiac magnetic resonance (CMR) imaging performed 2 to 6 days after study medication administration (first CMR) and again 12 ± 2 weeks later (second CMR).
Results:
In the efficacy cohort, the infarct size did not differ between groups on either the first CMR scan (n = 136; 15.8% LV mass [95% confidence interval {CI}, 13.3-18.2% LV mass] for the epoetin alfa group vs 15.0% LV mass [95% CI, 12.6-17.3% LV mass] for the placebo group; P = .67) or on the second CMR scan (n = 124; 10.6% LV mass [95% CI, 8.4-12.8% LV mass] vs 10.4% LV mass [95% CI, 8.5-12.3% LV mass], respectively; P = .89). In a prespecified analysis of patients aged 70 years or older (n = 21), the mean infarct size within the first week (first CMR) was larger in the epoetin alfa group (19.9% LV mass; 95% CI, 14.0-25.7% LV mass) than in the placebo group (11.7% LV mass; 95% CI, 7.2-16.1% LV mass) (P = .03). In the safety cohort, of the 125 patients who received epoetin alfa, the composite outcome of death, MI, stroke, or stent thrombosis occurred in 5 (4.0%; 95% CI, 1.31%-9.09%) but in none of the 97 who received placebo (P = .04).
Conclusions:
In patients with STEMI who had successful reperfusion with primary or rescue PCI, a single intravenous bolus of epoetin alfa within 4 hours of PCI did not reduce infarct size and was associated with higher rates of adverse cardiovascular events. Subgroup analyses raised concerns about an increase in infarct size among older patients.
Trial Registration:
clinicaltrials.gov Identifier: NCT00378352.
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