Benefit of restrictive transfusions with coronary surgery put in doubt

Secondary analysis of data from the TITRe2 trial found restrictive transfusion thresholds following cardiac surgery not superior to liberal thresholds when evaluating morbidity and cost at three months.

These findings, published March 12 in the New England Journal of Medicine, may not be what some in the field hoped.

The TITRe2 (Transfusion Indication Threshold Reduction) study evaluated outcomes for 2,003 patients enrolled at 17 U.K. cardiac surgery centers. Patients underwent nonemergency cardiac surgery. They were randomly assigned a liberal transfusion threshold, with a hemoglobin level of 9 g per deciliter, or a restrictive transfusion threshold, with a hemoglobin level of 7.5 g per deciliter. Patients were followed up at three months after surgery.

Researchers, led by Gavin J. Murphy, FRCS, of the Glenfield General Hospital in Leicester, U.K., then analyzed outcomes and cost between the two groups.

The mean hemoglobin level nadir was approximately 1 g per deciliter lower for patients assigned restrictive thresholds compared with those with liberal thresholds. Of patients in the restrictive threshold group, 53.4 percent received one or more transfusions; 92.2 percent of patients in the liberal threshold group received one or more transfusions.

Serious infections or ischemic events occurred to 35.1 percent of restrictive threshold patients and 33 percent of liberal threshold patients. Length of stay and rates of pulmonary complications were similar between the groups. However, there were nearly double the number of deaths amongst the restrictive threshold group compared with the liberal threshold group, leading to an increased risk profile for these patients (4.2 percent vs 2.6 percent, respectively; hazard ratio 1.64). In particular, 30-day mortality seemed to drive these numbers (2.6 percent vs. 1.9 percent, respectively).

Serious postoperative complications occurred more frequently among patients assigned a restrictive threshold (35.7 percent vs 34.2 percent).

Costs appeared to favor restrictive thresholds at first: Mean cost for red blood cell units were $479 (£287) for restrictive threshold patients and $713 (£427) for liberal thresholds. However, other cost components and total mean costs were relatively similar between the two groups at the three-month mark: $17,762 (£10,636) and $18,059 (£10,814) for restrictive thresholds and liberal thresholds, respectively.

The findings of Murphy et al contradicted some observational analysis but were consistent with others, including randomized controlled trials with critically ill and surgical patients. Instead of clarifying the issue, the authors admitted that this analysis adds “uncertainty regarding the use of restrictive threshold for cardiac surgery.”

They hypothesized that their findings may suggest that patients undergoing cardiac surgery may benefit from higher hemoglobin levels, being at the limits of their cardiovascular reserve.

“Patients with cardiovascular disease may represent a specific high-risk group for which more liberal transfusion thresholds are to be recommended. This hypothesis should be tested in future pragmatic trials,” Murphy et al wrote.