By Nicole Lou
Stricter approach deemed noninferior to liberal strategy in cardiac surgery
Being stricter on red-cell transfusion during cardiac surgery can save surgical departments valuable blood products without increasing risk for patients, a 5,000-person randomized trial showed.
Only if hemoglobin concentrations fell under 7.5 g/dL did patients get intraoperative and postoperative transfusion in a restrictive strategy by C. David Mazer, MD, of St. Michael’s Hospital in Toronto, and colleagues. This way, red-cell transfusion was given 52.3% of the time versus 72.6% with a more liberal transfusion strategy (OR 0.41, 95% CI 0.37-0.47).
Holding back on transfusing did not translate into worse outcomes for this group (by hospital discharge or 28 days after surgery): their combined rate of all-cause death, MI, stroke, or new-onset renal failure was non-inferior to that of peers who were transfused more liberally (11.4% for restrictive strategy vs 12.5% liberal strategy, OR 0.90, 95% CI 0.76-1.07, P<0.001 for noninferiority), according to the late-breaking TRICS III trial presented at the American Heart Association (AHA) meeting.
“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,” the trialists concluded. The data were simultaneously published online in the New England Journal of Medicine.
When MedPage Today asked about the cost savings associated with restricted transfusion, Mazer estimated that it was several million U.S. dollars saved just within the scope of the study.
Those in the restricted transfusion group who did end up getting transfused got received fewer blood units than did the liberal group (2 vs 3, OR 0.85, 95% CI 0.82-0.88).
Judging by mortality alone yielded no difference between groups (3.0% vs 3.6%, OR 0.85, 95% CI 0.62-1.16). Patients shared similar rates of other secondary outcomes as well.
“These findings from TRICS III are great news for patients,” commented Deepak Bhatt, MD, MPH, of Brigham and Women’s Hospital in Boston. “The investigators have shown rather conclusively that for patients undergoing cardiac surgery, a restrictive transfusion strategy is at least as good as a more liberal one. That means less transfusions for patients, less of the potential risks associated with transfusions, less use of a precious resource, and also lower costs — a win on all levels.” Bhatt was not involved in the research.
For the purposes of this study, liberal red-cell transfusion meant that patients were transfused if hemoglobin dropped below 9.5 g/dL in the operating room/ICU or below 8.5 g/dL while in the non-ICU ward. Transfusion strategy was followed from the induction of anesthesia to either hospital discharge or 28 days after surgery, whichever came first.
Investigators randomized more than 5,000 patients who were undergoing cardiac surgery with cardiopulmonary bypass to one of the two transfusion strategies in this trial. Participants were enrolled across 73 sites worldwide.
For their present analysis, Mazer’s group added 208 patients from their randomized TRICS II pilot study into the mix. They ended up with 5,092 patients in the modified intention-to-treat population (4,860 per-protocol, the basis for the primary outcome comparison). This was enough to give the authors 90% power to detect noninferiority with respect to the primary composite endpoint.
Altogether, patients went into cardiac surgery with a moderate-to-high mortality risk (a mean 7.8 points on EuroSCORE I). The study group was age 72 on average and 35.4% women. Hemoglobin concentrations were a mean 13.1 g/dL at baseline. Baseline characteristics were similar between the restrictive and liberal transfusion groups. Over half of patients got coronary artery bypass grafting with or without another concomitant procedure.
On subgroup analysis, it turned out that the restrictive strategy was associated with a lower composite outcome rate among those ages ≥75 (OR 0.70, 95% CI 0.54-0.89) but not the younger cohort (OR 1.17, 95% CI 0.91-1.50, P=0.004 for interaction).
While hypothesis-generating, this finding at least confirms that restrictive transfusion is safe in the elderly, according to the TRICS III researchers.
In addition, over the 28 days after cardiac surgery, the restrictive and liberal transfusion arms maintained hemoglobin concentrations of 9 g/dL and 10 g/dL, respectively.
The trial does not show that patients with hemoglobin values of 7.5 g/dL do as well as those with 9.5 g/dL, emphasized Vincent Gaudiani, MD, of the California Pacific Medical Center in San Francisco.
“Perhaps we can use the restrictive criterion and still end up with safe blood levels in our patients,” said Gaudiani, who was not involved in the study. “I will be more thoughtful about transfusion.” However, he said would not tolerate routine hemoglobin levels of 7.5 g/dL in his patients.
AHA discussant Frank Sellke, MD, of Alpert Medical School of Brown University in Providence, Rhode Island, saw the 1 g/dL difference in hemoglobin concentrations between groups and questioned if there was adequate adherence to protocol in the study.
Mazer’s group noted that they were unable to perform blinding for this trial, an important caveat. Their findings may not necessarily generalizable to low-risk patients, either.
Even so, Sellke called TRICS III an important trial, noting it was twice as large as the next largest trial.
The TRICS III trial was funded by the Canadian Institutes for Health Research, the Canadian Blood Services-Health Canada, the National Health and Medical Research Council of Australia, and the Health Research Council of New Zealand.