TRICS III: Restrictive Red-Cell Transfusion Noninferior to Liberal Use in Cardiac Surgery

ANAHEIM, CA—A large study conducted in 19 countries around the globe has found that a policy of restrictive red-cell transfusion during cardiac surgery with cardiopulmonary bypass (CPB) is just as safe and effective as more liberal transfusion protocols.

According to C. David Mazer, MD (St. Michael’s Hospital, Toronto, Canada), a restrictive red blood cell transfusion strategy of “is noninferior to a liberal strategy for mortality and major morbidity including myocardial infarction, stroke, or new onset of renal failure with dialysis in moderate-to-high-risk patients undergoing cardiac surgery.”

Mazer presented the TRICS III trial here at the American Heart Association 2017 Scientific Sessions; it was published simultaneously in the New England Journal of Medicine.

TRICS III enrolled 5,243 patients with a EuroSCORE I of 6 or higher who were scheduled for cardiac surgery with CPB. They were randomized to the restrictive protocol (start transfusion if hemoglobin levels fell below 7.5 g/dL, starting at the time of anesthesia induction) or liberal protocol (start at < 9.5 g/dL in the operating room and < 8.5 g/dL in the ward) then followed for a primary composite endpoint of all-cause mortality, MI, new renal failure with dialysis, or new focal neurological deficits. Mean age was 72, and mean EuroSCORE I was 7.8/7.9 in the two groups. Surgeries were a mix of CABG, valve, combination, or other non-CABG surgeries.

As Mazer showed here, the primary outcome was reached by 11.4% of patients in the restrictive group and in 12.5% in the liberal group, a difference that met criteria for noninferiority. Examined individually, none of the components of the primary endpoint were statistically different, but all numerically favored the restrictive approach. A range of secondary outcomes including ICU and hospital lengths of stay, infection, ventilation days, acute kidney injury, and others were no different between strategies. Subgroup analyses and intention-to-treat and per-protocol analyses found similar results, with the exception of an analysis that stratified patients by age. Here, patients younger than 75 fared better with a liberal transfusion strategy, whereas patients older than 75 had better outcomes with a restrictive transfusion strategy.

In their paper, Mazer et al note that surgeons have increasingly been adopting restrictive transfusion strategies out of concerns for the known risks of blood transfusions as well as observational studies linking transfusions with an increased risk of death and morbidity.

“The TRICS III trial provides compelling evidence that a restrictive transfusion strategy is as effective and safe as a liberal strategy in patients undergoing cardiac surgery,” they write.

Notable in TRICS III

Discussing the results in a morning press conference, Frank W. Sellke, MD (Brown Medical School and Rhode Island Hospital, Providence), called TRICS III “an incredibly important study,” pointing to a “multitude” of previous trials that have produced equivocal results. Moreover, “projections suggest that that there will be a significant lack of an adequate supply of blood in the future,” so efforts to reduce transfusions are particularly welcome.

For Sellke, one of the most intriguing study findings was seen in elderly patients, who had significantly fewer primary outcome events with the restrictive strategy. Sellke characterized this as “counterintuitive,” noting that “surgeons have a lower threshold for transfusion in older patients.”

Asked about this observation, Mazer told TCTMD that TRICS III investigators were also “surprised” by this finding and conducted additional analyses, ultimately confirming these results.

One explanation, he said, may be that surgeons are “preselecting” patients for surgery, such that “good” or “healthy” patients do just fine with restrictive transfusion strategies. It could also be that elderly patients are more sensitive to inflammatory, immune, or volume effects of transfusion compared with younger patients, he added.

“It has been commonly held that patients who are older should have a higher hemoglobin and should have higher threshold for transfusion,” Mazer observed. “Our study didn’t find that, and I think all we can say is that it is hypothesis-generating and in our study it clearly showed that restrictive transfusion may be safe in those patients.”

For Timothy Gardner, MD (Christiana Care Health System, Wilmington, DE), this may be the most important finding of the study, since the trend in most hospitals towards more restrictive policies has been resisted by surgeons concerned about their more senior patients.

“I think we worry about increasing the soft neurological injury that some people think can occur with cardiopulmonary bypass and [want to provide] adequate oxygen-carrying capacity for those patients that are at risk of dementia or delirium or so on,” Gardner told TCTMD. “But this is pretty convincing information. I think it will continue the trend that is occurring towards a more restrictive policy.”

Other questions remain open, the TRICS III investigators note, including uncertainty over the the appropriate transfusion thresholds in patients with acute coronary artery disease. A multicenter trial dubbed MINT (Myocardial Ischemia and Transfusion) is currently ongoing, they write.