MINNEAPOLIS – A single high dose of human recombinant erythropoietin given 2 days before heart surgery reduced blood transfusions by 65%, without substantially increasing mortality or morbidity in the prospective, randomized SHOT trial.
Patients who received 80,000 IU of erythropoietin (Eprex) in a single bolus plus iron supplementation until discharge needed 0.39 blood units/patient, compared with 1.12 units/patient for those receiving standard care involving thromboelastography and tranexamic acid (P less than .001; risk ratio, 0.338).
All-cause mortality at 45 days postoperative was 3.0% with erythropoietin and 3.33% without it (P = .26), Dr. Luca Weltert said at the annual meeting of the American Association for Thoracic Surgery.
Copyright Martin Allred
Dr. Luca Weltert
The investigators undertook the SHOT (Blood Sparing Strategies: Single Shot High Dose Erythropoietin Two Days Before Heart Surgery) trial because their original erythropoietin protocol proved too complicated for everyday use. The protocol was incorporated into the 2012 Society of Thoracic Surgeons and Society of Cardiovascular Anesthesiologists blood conservation clinical practice guidelines, but consisted of five different doses of erythropoietin in 5 days, totaling 52,000 IU, he explained.
Invited discussant Dr. Victor Ferraris, of the Lexington (Ky.) Veterans Affairs Medical Center, questioned whether the high dose of erythropoietin increased thromboembolic events, in light of the black box warnings added to erythropoiesis-stimulating agents due to an increased risk for thromboembolic events in patients with malignancy and an increased risk of serious cardiovascular events in patients with chronic kidney disease when the hemoglobin level exceeds 12 g/dL.
Thromboembolic events were not significantly different between groups, and the trial did not include cancer patients, said Dr. Weltert of the European Hospital in Rome.
Major nonfatal adverse events at 45 days were reported in 4.33% of erythropoietin and 5.67% of control patients (P = .13). Specifically, there were no differences in neurologic complications (4 vs. 5 events, respectively), long-term wound infection (4 in both groups), deep vein thrombosis (2 vs. 5), onset of acute hypertension (1 vs. 2), and new-onset renal failure (2 vs. 1).
Attendees continued this line of questioning, asking how reliable the negative finding is and whether the investigators could have missed a population with a positive result. The efficacy endpoint was based on a minimal sample size of 400 patients, and the trial enrolled 600 consecutive "all comers," Dr. Weltert said, but he added that 3,000 to 4,000 patients would be needed for the safety endpoint, "so the samples are ridiculously small to really state strongly that there is no harm for a subgroup."
The two study arms were well matched, with 35% of all patients undergoing coronary artery bypass grafting, 31% valve surgery, roughly 20% repair of the ascending aorta, and other in about 14%. The mean logistic EuroScore was 9.94 in the erythropoietin group and 10.12 in the control group, and the mean ages were 72.9 and 70.4 years, respectively.
Mean hemoglobin levels on day 4 postoperative was significantly higher in the erythropoietin group than in controls (10.21 vs. 9.01 g/dL; P = .02), Dr. Weltert said.
There were no significant differences between the erythropoietin and control groups in intensive care unit stay (2.71 vs. 2.60 days, respectively), perioperative myocardial infarction (7 vs. 7), cardiac tamponade (3 vs. 5), or need for reintubation (13 vs. 15).
An attendee asked whether hemoglobin levels drifted between days 3 and 4 postoperatively, as this can confound the decision to transfuse after cardiac surgery, and whether the investigators looked at another potential confounder, hemoglobin trigger, since no less than five randomized controlled trials have shown that a hemoglobin level of 7-8 g/dL should be used as a transfusion trigger.
Dr. Weltert said the team picked day 4 to check hemoglobin levels for practical reasons because that’s the day when you see the biggest drift and that the erythropoietin group fared better. He went on to say, "The trigger is extremely important, and I think it will be the very next step in bloodless surgery."
The investigators did compare costs for the two strategies, with standard care ringing up at 336 euros (U.S.$434), vs. 297 euros (U.S.$383) for the erythropoietin protocol (P = .05).
The European Hospital sponsored the study. Dr. Weltert reported no relevant disclosures.