Effect of erythropoietin as an adjunct to primary percutaneous coronary intervention: a randomised controlled clinical trial

Abstract

Objective The acute administration of high-dose erythropoietin (EPO) on reperfusing ischaemic myocardium has been reported to halve myocardial infarct (MI) size in preclinical studies, but its effect in ST elevation myocardial infarction patients undergoing primary percutaneous coronary intervention (PPCI) remains unknown. We investigated whether high-dose EPO administered as an adjunct to PPCI reduces MI size. Design Double-blinded, randomised, placebo-controlled. Setting Single tertiary cardiac centre. Patients Fifty-one ST elevation myocardial infarction patients undergoing PPCI. Interventions Patients were randomly assigned to receive either a single intravenous bolus of EPO (50 000 IU) prior to PPCI with a further bolus given 24 h later (n¼26) or placebo (n¼25). Main outcome measures MI size measured by 24 h area under the curve troponin T and cardiac magnetic resonance imaging performed on day 2 and at 4 months. Results EPO treatment failed to reduce MI size (troponin T area under the curve: 114.6678 mg/ml EPO vs 100.8668 mg/ml placebo; infarct mass by cardiac magnetic resonance: 33616 g EPO vs 25616 g placebo; both p>0.05). Unexpectedly, EPO treatment doubled the incidence of microvascular obstruction (82% EPO vs 47% placebo; p¼0.02) and significantly increased indexed left ventricular (LV) end-diastolic volumes (84610 ml/m 2 EPO vs 73613 ml/m 2 placebo; p¼0.003), indexed LV end-systolic volumes (4169 ml/m 2 EPO vs 35611 ml/m 2 placebo; p¼0.035) and indexed myocardial mass (89616 g/m 2 EPO vs 79611 g/m 2 placebo; p¼0.03). At 4 months, there were no significant differences between groups. Conclusions High-dose EPO administered as an adjunct to PPCI failed to reduce MI size. In fact, EPO treatment was associated with an increased incidence of microvascular obstruction, LV dilatation and increased LV mass. Clinical Trial Registration Information http://public. ukcrn.org.uk/search/StudyDetail.aspx?StudyID¼4058 Unique Identifier¼Study ID 4058.

Almanac 2012: Cardiovascular risk scores: The national society journals present selected research that has driven recent advances in clinical cardiology

“…80 In one study the effect of erythropoietin was tested based on beneficial experi-mental effects for reducing infarct size. 81 However, the study was negative, with patients randomised to erythropoietin (50 000 IU) before primary PCI showing an increased incidence of microvascular obstruction and LV dilata tion without reduction in infarct size compared with patients randomised to placebo. Another study using forearm plethysmography tested a bradykinin B2 receptor antagonist, based on the hypothesis that endogenous bradykinin is a mediator of reperfusion injury.…”

Almanac 2012: Interventional cardiology

“…80 In one study the effect of erythropoietin was tested based on beneficial experimental effects for reducing infarct size. 81 However, the study was negative, with patients randomised to erythropoietin (50 000 IU) before primary PCI showing an increased incidence of microvascular obstruction and LV dilatation without reduction in infarct size compared with patients randomised to placebo. Another study using forearm plethysmography tested a bradykinin B2 receptor antagonist, based on the hypothesis that endogenous bradykinin is a mediator of reperfusion injury.…”

Pharmacologic Therapy That Simulates Conditioning for Cardiac Ischemic/Reperfusion Injury

“…In fact, there was an increased incidence of microvascular obstruction (MVO), left ventricular (LV) dilation, and LV mass in the group that received EPO. 65 Similarly, in the REVEAL study, investigators who randomized 222 patients to receive 60 000 IU of EPO within 4 hours of reperfusion found no reduction in infarct size and a higher rate of adverse cardiovascular outcomes (death, MI, stroke, and stent thrombosis). Furthermore, a subgroup analysis revealed larger infarct sizes in older patients.…”