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REVEAL: Epoetin alfa potentially harmful in patients with STEMI after PCI
Najjar S. JAMA. 2011;305:1863-1872.
Bhatt D. JAMA. 2011;305:1908-1909.
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Epoetin alfa administered to patients with STEMI within 4 hours of successful percutaneous coronary intervention was shown to increase the rate of adverse CV events while having no benefit on infarct size.
The Reduction of Infarct Expansion and Ventricular Remodeling with Erythropoietin after Large Myocardial Infarction (REVEAL) trial was a phase 2 study that included 222 patients with STEMI who were successfully treated with PCI. Patients were randomly assigned to either treatment with IV epoetin alfa or matching placebo delivered within 4 hours of the procedure. Physicians then measured infarct size with cardiac MRI between 2 to 6 days after drug administration and then again 12 weeks later, and they expressed findings as percent of left ventricular mass.
According to results, infarct size at both first (epoetin alfa, 15.8% vs. placebo, 15%) and second (epoetin alfa, 10.6% vs. placebo, 10.4%) MRI scan did not differ between those given 60,000 units of epoetin alfa and placebo. However, for patients aged at least 70 years, mean infarct size in the first week was larger among those in the epoetin alfa group (19.9% vs. 11.7%; P=.03).
The researchers then performed safety analysis, which included a dose escalation of epoetin alfa (15,000 units, 30,000 units and 60,000 units), which revealed a higher rate of any adverse event in those who received epoetin alfa (55.2% vs. 41.2%; P=.04), which was also true of serious adverse events (20% vs. 10.3%; P=.05). Furthermore, the composite outcome of death, MI, stroke or stent thrombosis occurred only in the epoetin alfa group (4% vs. 0%; P=.04).
Considering the results of this study, Deepak L. Bhatt, MD, MPH, with the VA Boston Healthcare System, wrote in an accompanying editorial that it may not be worth taking epoetin alfa into phase 3 trials.
“Several compounds to limit infarct size or to mitigate reperfusion injury have appeared promising in animal models, only to fail when tested in humans,” Bhatt said. “Use of cardiac MRI may allow screening of several future candidate compounds in studies with reasonable sample sizes and may reveal those that appear most promising for reducing infarct size. Investigators can then conduct large clinical trials to evaluate those approaches that are likely to yield benefit and not cause harm.”
Disclosure: Dr. Bhatt reports receiving research support from AstraZeneca, Bristol-Myers Squibb, Eisai, Sanofi-Aventis and The Medicines Company.
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