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Restrictive vs. Liberal Red Blood Cell Transfusion in Cardiac Surgery: 6-Month Data from TRICS III

February 01, 2019.
C David Mazer, MD, Toronto, ON

Educational Objectives


After completing the activity, the clinician will be better able to compare the results of a restrictive versus liberal strategy of red blood cell transfusion in patients with a moderate-to-high risk of death after cardiac surgery.

Summary


Interviewer: Carl J. Pepine, MD, MACC

Take-home Messages:

  • While anemia is independently associated with adverse outcomes, red blood cell transfusion is associated with increased mortality in observational studies.
  • In evaluating 6-month follow-up data, investigators report that a restrictive red blood cell transfusion strategy is noninferior to a liberal strategy for mortality and major morbidity in patients who were at moderate-to-high predicted risk for death undergoing cardiac surgery using cardiopulmonary bypass.
  • One finding is in conflict with current clinical practice. Subgroup analysis suggested that in older patients, the restrictive strategy appeared to be superior to the liberal strategy; whereas, in patients younger than 75 years, the liberal strategy was associated with a lower risk of the composite outcome than the restrictive strategy.

A substantial proportion of the total transfusion blood supply goes to patients undergoing cardiac surgery. The avoidance of unnecessary blood transfusion is a high priority. Whether a restrictive approach could achieve results similar to those of a more liberal transfusion strategy in cardiac surgery was unclear until Mazer et al. reported their results of a randomized trial of 5,243 adults who were at moderate-to-high risk for death and who were undergoing cardiac surgery.1

The found that a restrictive strategy of red-cell transfusion was noninferior to a liberal strategy with respect to the composite outcome of death from any cause, myocardial infarction, stroke, or new-onset renal failure with dialysis by hospital discharge or by day 28, whichever came first. Their results confirmed the findings of a smaller study reported several years earlier, also with short-term (30-day) follow-up.2

While anemia is independently associated with adverse outcomes, clinicians have increasingly been adopting restrictive transfusion strategies in cardiac surgery, largely because of the known risks of blood transfusions and because observational studies have linked transfusion with increased mortality and major morbidity. Adding to the concern are findings from observational and randomized studies suggesting the deleterious effects of transfusion on longer-term outcomes.

TRICS III
Therefore, C. David Mazer, MD, a professor at the University of Toronto, and colleagues conducted the TRICS (Transfusion Requirements in Cardiac Surgery) III trial to compare a restrictive transfusion strategy to a liberal strategy in patients undergoing cardiac surgery. The patients were undergoing cardiopulmonary bypass surgery, and they had at least a moderate risk of death.

To overcome some of the limitations of previous trials, the investigators designed TRICS III to include a wide range of hospitals and countries, and they enrolled more than 5,000 patients.

The restrictive red-cell transfusion strategy was defined as transfusion if the hemoglobin concentration was <7.5 g/dL intraoperatively or postoperatively. The liberal strategy was transfusion if the hemoglobin concentration was <9.5 g/dL intraoperatively or postoperatively when the patient was in the intensive care unit (ICU), or <8.5 g/dL if the patient was in the non-ICU ward.

In short (see Table for details),3 there was no significant difference between the 2 strategies with respect to the composite outcome of death from any cause, myocardial infarction, stroke, or new-onset renal failure requiring dialysis at 6 months after surgery (p = 0.006 for noninferiority). There were no significant between-group differences in secondary outcomes, either, including the individual components of the composite primary endpoint, coronary revascularization, and hospital readmission or emergency department visit.

Subgroup analysis showed no impact on the primary endpoint based on the presence of diabetes, creatinine clearance, left ventricular function, chronic pulmonary disease, surgery category (coronary artery bypass graft only vs. noncoronary artery bypass graft, or a combination), or preoperative hemoglobin concentration.

Only one variable seemed to influence outcome: age. At 6 months, there was an interaction between age and transfusion threshold. Specifically, in patients 75 years or older, the restrictive strategy appeared to be superior to the liberal strategy, whereas in patients younger than 75 years, the liberal strategy was associated with a lower risk of the composite outcome than the restrictive strategy.

While age was not statistically significant on its own, the interaction was robust in a series of sensitivity analyses, including adjusting for all the variables used to define subgroups. Across the 6 age groups evaluated, the p value for interaction was 0.004.

At this point, the finding should be considered hypothesis generating. Other studies are needed to evaluate the result, which seems at odds with current clinical practice, in which a liberal transfusion strategy is used in older patients undergoing cardiac or noncardiac surgery.

TRICS III: Outcomes at 6 Months Based on Transfusion Strategy

 

Restrictive Strategy
(n = 2,317)

Liberal ­Strategy
(n = 2,347)

Odds Ratio
(95% CI)

Primary outcome*

17.4%

17.1%

1.02
(0.87-1.18)

Mortality

6.2%

6.4%

0.95
(0.75-1.21)

Hospital readmission or ED visit

35.5%

33.6%

1.09
(0.96-1.23)

*Composite of death from any cause, myocardial infarction, stroke, or new-onset renal failure with dialysis within 6 months after the index surgery.
CI = confidence interval; ED = emergency department.

Readings


  1. Mazer CD, Whitlock RP, Fergusson DA, et al. Restrictive or liberal red-cell transfusion for cardiac surgery. N Engl J Med 2017;377:2133-44.
  2. Hajjar LA, Vincent JL, Galas FR, et al. Transfusion requirements after cardiac surgery: the TRACS randomized controlled trial. JAMA 2010;304:1559-67.
  3. Mazer CD, Whitlock RP, Fergusson DA, et al. Six-Month Outcomes After Restrictive or Liberal Transfusion for Cardiac Surgery. N Engl J Med 2018;379:1224-33.

Disclosures


C David Mazer, MD, Toronto, ON
This author has nothing to disclose.

Interviewer: Carl J. Pepine, MD, MACC
This author has nothing to disclose.

Acknowledgements


CME/CE INFO

Accreditation:
Lecture ID:

AC510214

Qualifies for:

ABIM MOC

Expiration:

This CME course qualifies for AMA PRA Category 1 Credits™ for 3 years from the date of publication.

Instructions:

To earn CME/CE credit for this course, you must complete all the following components in the order recommended: (1) Review introductory course content, including Educational Objectives and Faculty/Planner Disclosures; (2) Listen to the audio program and review accompanying learning materials; (3) Complete posttest (only after completing Step 2) and earn a passing score of at least 80%. Taking the course Pretest and completing the Evaluation Survey are strongly recommended (but not mandatory) components of completing this CME/CE course.

Estimated time to complete this CME/CE course:

Approximately 2x the length of the recorded lecture to account for time spent studying accompanying learning materials and completing tests.

More Details - Certification & Accreditation