Erythropoietin Bolus After PCI Fails to Reduce Infarct Size

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Avoid Erythropoietin in Anyone at MI Risk

The results of this rigorous clinical trial "seem to settle the debate about whether there is a therapeutic role for erythropoietin administration during primary PCI [percutaneous coronary intervention] and is a useful negative finding," said Dr. Deepak L. Bhatt.

Moreover, the safety findings raise concerns about the use of epoetin alfa for any indication – including anemia, for which it is widely prescribed – in patients likely to develop MI.

"The totality of evidence strongly suggests that this class of medication has cardiovascular risk, most likely to manifest in higher-risk individuals. Until compelling data become available to support routine use of these agents in patients with anemia, it would be prudent to minimize their use, especially for patients at high risk for cardiovascular disease or with an acute ischemic syndrome," Dr. Bhatt said.

When the use of erythropoietin is necessary, "it will be important to educate patients about the potential risks of ischemia so they are aware of the signs and symptoms and know to seek help should an ischemic or thrombotic syndrome develop," he added.

Dr. Bhatt is with the Veterans Administration Boston Healthcare System, Brigham and Women’s Hospital, and Harvard Medical School, Boston. He reported ties to AstraZeneca, Bristol-Myers Squibb, Eisai, Sanofi-Aventis, and the Medicines Company. He has received honoraria from Duke Clinical Research Institute unrelated to the REVEAL study. These remarks were taken from his editorial accompanying Dr. Najjar’s report (JAMA 2011;305:1908-9).



An intravenous bolus of epoetin alfa in ST-segment elevation myocardial infarction patients who have successful primary or rescue percutaneous coronary intervention does not reduce infarct size, according to a report in the May 11 issue of JAMA.

To the contrary, the treatment was associated with an increased infarct size in the subgroup of patients older than age 70 years, said Dr. Samer S. Najjar of the MedStar Health Research Institute at Washington Hospital Center and his associates.

In addition, the erythropoietin bolus increased the rate of adverse cardiovascular events, including stent thrombosis. Taken together with the results of previous studies, these findings "indicate that no clinical study to date has shown any beneficial effect of erythropoietin on infarct size measured by cardiac magnetic resonance."

Moreover, "Due to ... safety findings, temporary withholding of erythropoietin in patients who are receiving this medication for labeled indications and who sustain an MI merits further study," they added.

Preclinical and animal studies have demonstrated that beyond its effects on red blood cell production, erythropoietin is cardioprotective during ischemia and reperfusion, significantly reducing infarct size and improving left ventricular (LV) function, presumably through its antiapoptotic and angiogenic properties. Dr. Najjar and his colleagues performed a phase II multicenter clinical trial to assess the safety and efficacy of receiving a single IV bolus of epoetin alfa within 4 hours of successful percutaneous coronary intervention (PCI) in 222 ST-segment elevation myocardial infarction (STEMI) patients.

The Reduction of Infarct Expansion and Ventricular Remodeling With Erythropoietin After Large Myocardial Infarction (REVEAL) study subjects were enrolled at 22 U.S. medical centers, stratified according to age and infarct location, and randomly assigned to receive either epoetin alfa or saline placebo infusion in a double-blind fashion. They underwent cardiac magnetic resonance imaging (CMR) to assess infarct size 2-6 days after receiving the infusion, then again after 12 weeks.

The primary efficacy end point – infarct size at the first CMR measurement – was no different between patients who received active medication and those who received placebo, the investigators said (JAMA 2011;305:1863-72).

There also was no difference between the two groups in infarct size at 12 weeks nor in infarct mass at either time point.

In a subgroup analysis, patients aged 70 years and older showed a 41% increase in mean infarct size with active treatment. In older patients who received epoetin alfa, the infarct was approximately 20% of the entire LV mass, compared with only 12% in the placebo group.

The rates of adverse events (55%) and serious adverse events (20%) were significantly higher with epoetin alfa than with placebo (41% and 10%, respectively). The composite outcome of death, MI, stroke, or stent thrombosis occurred in 4% of the group receiving active treatment, compared with 0% in the placebo group.

Taken together with the results of previous studies, these clinical trial findings confirm that "the promising cytoprotective effects of erythropoietin observed in animal models have not been reproduced in clinical studies of acute MI," Dr. Najjar and associates said.

Dr. Najjar’s study was sponsored by the National Institute on Aging. Centocor Ortho Biotech provided the study medication and Florida Biologix provided the matching placebo. Dr. Najjar and his associates reported ties to numerous industry sources.

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