Liberal Transfusions Do Not Appear to Offer Advantage Over Restrictive Strategy in High-Risk Cardiac Patients Post-Surgery

The use of a liberal transfusion strategy did not reduce the rates of mortality or major ischemic events among patients at high cardiac risk who had undergone a major vascular or general surgery procedure compared with those who were given a more restrictive transfusion approach, according to new research. The findings come from the Transfusion Trigger after Operations in High Cardiac Risk Patients (TOP) trial, published Nov. 8 in JAMA.

The rate of the composite primary outcome, all-cause death or major ischemic events, was comparable between the two groups: 9.1% for the liberal group and 10.1% for the restrictive group. Major ischemic events included myocardial infarction, coronary revascularization, acute kidney failure or ischemic stroke within 90 days of randomization.

The study enrolled 1,424 U.S. veterans at 16 Veterans Affairs medical centers (712 in each arm). The transfusion trigger was a hemoglobin (Hb) level of 10 g/dL or greater in the liberal arm and 7 g/dL or greater in the restrictive arm. Participants had a mean age of 69.9 years, and nearly all were male (97.8%). Most underwent vascular surgery and had multiple cardiovascular comorbidities.

On day 1 of randomization, mean Hb levels were 9.3 g/dL in the liberal group and 9.0 g/dL in the restrictive group. In the liberal group, 27.8% received one unit of blood and 65.7% received two or more units after randomization, whereas 77% of patients in the restrictive group received no transfusion.

While there was no statistical difference between the two groups for the combined composite endpoint, cardiac complications other than myocardial infarction were more frequent in the restrictive group (9.9% versus 5.9%). This difference was primarily driven by new-onset arrhythmias requiring treatment (4.3% versus 2.6%) and new or worsening heart failure (5.8% versus 4%).

The authors speculated that “the underlying pathophysiology is likely complex because in addition to the effect of anemia, differences in the amount and rate of intravenous fluid administration and diuretic use are important contributory factors.”

In an accompanying editorial, Jeremy W. Jacobs, MD; and Evan M. Bloch, MD, agreed, writing that “this finding suggests a complex pathophysiology, highlighting that prolonged anemia itself may exacerbate myocardial ischemia, which in turn can impair contractility and precipitate heart failure.”

Secondary outcomes included infectious complications (surgical site infections, pneumonia and sepsis) and cardiac complications other than myocardial infarction (new cardiac arrhythmias necessitating pharmacological or other treatment, new or worsening heart failure and cardiac arrest not resulting in death) within 90 days of randomization.

Mortality at 90 days was similar across groups: 4.6% in the liberal group and 4.7% in the restrictive group. Coronary revascularization and acute kidney failure occurred in 1.2% and 2.1% of patients in the liberal group, respectively, and 1.9% and 1.7%, respectively, in the restrictive group.

The event rate was lower than anticipated, thereby reducing the power of the trial to detect a statistically significant difference in the primary endpoint, though the authors concluded this was unlikely to affect its clinical relevance.

Jacobs and Bloch suggested that, based on the study’s findings, “a more nuanced approach may be indicated for those patients with severe heart failure, recent acute coronary syndromes, or poorly controlled arrhythmias, particularly in the postoperative setting.”