MUNICH – in a large, randomized trial presented at the annual congress of the European Society of Cardiology, and published simultaneously in the New England Journal of Medicine.
The investigators previously reported that 28 day outcomes were non-inferior with the restrictive approach, but they wanted to look into 6 month results to rule out latent problems, such as sequelae from perioperative organ hypoxia.
The new outcomes from the study, dubbed the Transfusion Requirements in Cardiac Surgery (TRICS) III trial, offer some reassurance at a time when cardiac surgeons are shifting towards more restrictive transfusion policies (N Engl J Med. 2018 Aug 26.doi: 10.1056/NEJMoa1808561).
The trial randomized 2,317 patients to red cell transfusions if their hemoglobin concentrations fell below 7.5 g/dL intraoperatively or postoperatively. Another 2,347 were randomized to the liberal approach, with transfusions below 9.5 g/dL in the operating room and ICU, and below 8.5 g/dL outside of the ICU. The arms were well matched, with a mean score of 8 in both groups on the 47-point European System for Cardiac Operative Risk Evaluation I score.
M. Alexander Otto/Frontline Medical News
Dr. David Mazer
At 6 months, 17.4% of patients in the restrictive arm, versus 17.1% in the liberal-threshold group, met the primary composite outcome of death from any cause, myocardial infarction, stroke, or new onset renal failure with dialysis (P = .006 for noninferiority with the restrictive threshold); 6.2% of patients in the restrictive-threshold group, versus 6.4% in the liberal-arm, had died at that point, a statistically insignificant difference.
Also at 6 months, 43.8% of patients in the restrictive-threshold group, versus 42.8% in the liberal arm, met the study’s secondary composite outcome, which included the components of the primary outcome plus hospital readmissions, ED visits, and coronary revascularization. The difference was again statistically insignificant.
The restrictive strategy saved a lot of blood. Just over half of the patients, versus almost three-quarters in the liberal arm, were transfused during their index admissions. When transfused, patients in the restrictive arm received a median of 2 units of red cells; liberal-arm patients received a median of 3 units.
Unexpectedly, patients 75 years and older had a lower risk of poor outcomes with the restrictive strategy, while the liberal strategy was associated with lower risk in younger subjects. The findings “appear to contradict” current practice, “in which a liberal transfusion strategy is used in older patients undergoing cardiac or noncardiac surgery,” said investigators led by C. David Mazer, MD, a professor in the department of anesthesia at the University of Toronto.
“One could hypothesize that older patients may have unacceptable adverse effects related to transfusion (e.g., volume overload and inflammatory and infectious complications) or that there may be age-related differences in the adverse-effect profile of transfusion or anemia. ... Whether transfusion thresholds should differ according to age” needs to be determined, they said.
The participants were a mean of 72 years old, and 35% were women. The majority in both arms underwent coronary artery bypass surgery, valve surgery, or both. Heart transplants were excluded. The trial was conducted in 19 countries, including China and India; results were consistent across study sites.
The work was funded by the Canadian Institutes of Health Research, among others. Dr. Mazer had no relevant disclosures.
SOURCE: Mazer CD et al. N Engl J Med. 2018 Aug 26. doi:10.1056/NEJMoa1808561