Recombinant Human Erythropoietin (rHuEpo): Lack of Effect on Response to ASA or Clopidogrel
September 21, 2007 by Rene Franco MD
New Haven, CT.- Short term use of Recombinant Human Erythropoietin (rHuEpo) has been shown to significantly reduce infarction size and decrease both left ventricular remodeling and fall in ejection fraction in animal models(1). rHuEpo however has also been associated with an increased risk of thrombotic events, in part due to the raise in hematocrit but probably by antagonizing the antiplatelet effects of aspirin (ASA). Previous studies on chronic kidney disease (CKD) patients have shown rHuEpo to decrease bleeding time in patients receiving aspirin treatment(2). Studies to evaluate the effects of rHuEpo in the human heart with ischemic injury have not yet been developed mainly because the reduction in the antiplatelet effects of aspirin poses a potential risk in patients with ischemic heart disease . A study comparing the interaction of ASA and rHuEpo on patients without known platelet dysfunction would open the door to evaluate the impact of short term rHuEpo administration on patients with ischemic heart disease, in whom ASA is essential part of the management and antagonizing its effect is potentially deleterious.
In the last issue of the American Heart Journal Yi-Da Tang MD and colleagues, from the Section of Cardiovascular Medicine and Laboratory Medicine at Yale University School of Medicine, report the results of a double-blind randomized study of 96 healthy patients who received placebo versus different doses of rHuEpo. Four treatment groups were randomly created; doses of 100, 200 and 400 U/Kg were given respectively for three consecutive days, with the fourth group receiving Normal Saline injection as a placebo. After receiving the last dose, all patients were randomly assigned to receive either aspirin 325mg or clopidogrel 300mg by mouth.
The outcome variables measured were the bleeding time and platelet function assay (PFA). These were determined before the first dose of the study drug; immediately after the last dose; at 5 hours and at 1, 5, and 7 days after administration of aspirin or clopidogrel.
After receiving the 3 day rHuEpo doses and before the administration of aspirin or clopidogrel no significant change was observed in the bleeding time of any of the 4 groups; all P values >.20. Bleeding time increased significantly in all study groups after the administration of aspirin (ASA)325mg and clopidogrel 300mg compared with pretreatment values in all treatment groups.
rHuEpo at the 100 and 200U/Kg did not modify significantly the bleeding time responses to aspirin or clopidogrel when compared to the control group. On the other hand a 400U/Kg dose significantly decreased bleeding time at 5 hours(p=.03) and 1 day (p=.01) after ASA administration. An impact in the platelet count was also noted with the rHuEpo 400U/Kg dose. A significant increase (p=0.014) after 5 days and a tendency of platelet count to continue raising was also noted in the 7th day.
PFA-EPI closure times after administration of ASA and of Clopidogrel did not differ significantly between treatment groups at any point.
This study suggests that co-administration of ASA or Clopidogrel along with low dose rHuEpo (<400U/Kg) does not modify the original antiplatelet effect of either drug in patients without known platelet dysfunction or any known co-morbidities.
Further studies, including CAD patients, in whom ASA and clopidogrel are essential part of the management, might help better describe the role of rHuEpo in the human myocardial ischemic injury.
- ref1 pmid=16187008
- ref2 pmid=17719296