NEW ORLEANS — In people with high cardiac risk undergoing major surgery, initiating blood transfusions earlier than currently recommended may not reduce their chances of having a heart attack or stroke, but it may reduce their chances of having heart failure or arrhythmias after surgery, a clinical trial of veterans showed. 

“This trial does underscore that the decision to infuse high cardiac risk patients after major surgery is nuanced and that a one-size-fits-all transfusion strategy may not be best,” said Panos Kougias, MD, MSc, chair of the Department of Surgery at Downstate Health Sciences University in Brooklyn. 

Kougias presented results from the TOP trial during a presentation at the American Heart Association (AHA) Scientific Sessions 2025. Results were published simultaneously in the JAMA. 

No Reduction in Major Events

The TOP trial compared the guideline-recommended strategy of initiating transfusion when patients’ hemoglobin levels drop below 7 g/dL, known as the restrictive strategy, with a more liberal strategy that triggers transfusion when levels drop below 10 g/dL. The study randomly assigned 1428 patients from 16 Veterans Affairs medical centers to the restrictive or liberal transfusion groups. The final analysis included 712 patients with hemoglobin levels below 10 g/dL in each group.

“Postoperative anemia is common after major vascular and general surgery operations,” said co-investigator Sherene Sharath, PhD, MPH, director of clinical and health services research for the Department of Surgery at Downstate Health Sciences University, Brooklyn. “Guidelines recommend transfusion for hemoglobin below 7 g/dL. However, the safety of this strategy after major operations in high cardiac risk patients is unclear.”

The primary outcome was a composite of all-cause death, myocardial infarction, coronary revascularization, acute renal failure, or ischemic stroke within 90 days of receiving the transfusions. The secondary outcome was a composite of complications other than myocardial infarction, including new or worsening heart failure, new cardiac arrhythmia, or nonfatal cardiac arrest.

“We cannot claim that the liberal strategy is superior for the primary outcome,” Kougias said. “However, the liberal strategy may provide a clinical benefit by reducing the risk for heart failure and arrhythmias.”

The rate of the primary outcome in the liberal group was 9.1% vs 10.1% in the restrictive group (relative risk [RR], 0.9; 95% CI, 0.65-1.24). However, the rate of nonmyocardial complications was significantly lower in the liberal group (5.9% vs 9.9%; RR, 0.59; 95% CI, 0.36-0.98), he said. 

“We have to remember this was a secondary outcome that was not adjudicated,” Kougias said. “So, although the difference is large and worth taking notice of, we should interpret this finding with caution.”

Other secondary outcomes, including infectious complications, 1-year mortality and length of stay, were similar between the two groups, he added. 

More Research Necessary

“We know that acute anemia is bad in any clinical setting and when we get to the bottom of it, the reason that it is bad for patient outcomes is that it induces a cascade of unfortunate events and those would include hypotension, stasis, sympathetic activation, along with decreased tissue oxygenation, hypoperfusion of end organs, and ultimately resulting in shock,” said discussant Louise Sun, MD, SM, director of cardiovascular research at Stanford University School of Medicine in Palo Alto, California.

“However, transfusion may not necessarily be the answer to every case of acute blood-loss anemia,” she said. “Transfusions have complications.”

She noted the shift toward restrictive transfusion thresholds across medicine, and cited the 2023 report of the Ottawa Intraoperative Transfusion Consensus, which advises a hemoglobin level of 7 g/dL as an acceptable threshold for transfusions in patients who do not have major cardiovascular risks.

In most cases, clinicians are “very comfortable” with the 7-g/dL threshold, according to Sun. 

“But why is it that in certain instances, we’re a little uncomfortable with that threshold?” she said. “We try to personalize our transfusion practices; that’s an area that major trials haven’t been able to explore so far.”

She cited the Transfusion Requirements in Cardiac Surgery (TRICS) III trial, which found lower rates of myocardial infarction, stroke, and dialysis with the restrictive strategy in patients aged 75 years and older but not among younger patients. This finding makes a case for future trials evaluating special groups, including age, Sun said. Longer-term follow-ups would also be needed, as well as evaluation of nonphysiologic outcomes such as quality of life. 

Kougias, Sharath and Sun have no relevant disclosures. 

Richard Mark Kirkner is a medical journalist based in Philadelphia.