Investigators said the finding indicates that a restrictive transfusion strategy might not be beneficial in men with high cardiac risk who undergo these types of operations. The study was presented at the 2019 annual meeting of the American Surgical Association.

Researchers suggest a review of transfusion strategies in men with high cardiac risk undergoing major general and vascular surgery procedures.

In an analysis of more than 140,000 cases, poor outcomes were seen in relation to anemia at hemoglobin levels of 10 g/dL—a rate higher than many triggers for liberal transfusion.

“From this data, this analysis raises the interesting possibility that it may be more beneficial to transfuse a bit faster in these patients than what most people do today,” said principal investigator Panos Kougias, MD, MSc, an associate professor at Baylor College of Medicine and the chief of vascular surgery at the Michael E. DeBakey VA Medical Center in Houston. Dr. Kougias presented the results.

There is no clear threshold for when patients should be transfused after surgery. The American Association of Blood Banks strongly recommends adhering to a restrictive transfusion strategy of 7 to 8 g/dL in hospitalized, stable patients. The organization made a “weak” recommendation, based on moderate quality evidence, of adhering to a restrictive strategy in hospitalized patients with preexisting cardiovascular disease and considering transfusion for patients with symptoms of a hemoglobin level of 8 g/dL or lower.

Much of the evidence on transfusion triggers and anemia comes from surgical specialties outside of general surgery. To address this gap, Dr. Kougias and his colleagues conducted a retrospective study of patients who underwent major vascular or general surgery in the Veterans Health Administration system between January 2000 and December 2015. Any patients undergoing dialysis, endovascular or low-risk laparoscopic procedures were excluded. Patients were defined as having high cardiovascular risk if there was a history of ischemic heart disease, stroke or peripheral artery disease. Primary end points were death, myocardial infarction, acute renal failure, coronary revascularization or stroke within 90 days postoperatively.

Of the 142,510 surgical procedures performed at 91 institutions, 56% of the 64,557 vascular surgery patients and 14% of the 77,953 general surgery patients were high cardiac risk. The mean age was 65 years; patients with high cardiac risk were older and more likely to have a history of hyperlipidemia, hypertension, chronic obstructive pulmonary disease and diabetes.

More than 95% of the patients in this study were men. Investigators cautioned the results cannot be extrapolated to women undergoing similar operations.

The study found that the strongest predictor of the primary end points was postoperative anemia, with an increased risk of 47% for every 1 g/dL decrease in postoperative nadir hemoglobin, measured over 15 days postoperatively. High cardiovascular risk also independently predicted the primary end points in an additive fashion when postoperative nadir hemoglobin fell below 10 g/dL.

“High cardiac risk modifies the effect of postoperative anemia on mortality or major ischemic events after these surgical interventions,” said Dr. Kougias. “These findings support the notion that high-cardiac-risk patients may respond to postoperative anemia differently from their non–high-cardiac-risk counterparts.”

After the study was presented at ASA, Mary Hawn, MD, a professor and the chair of surgery at Stanford University in California, said most randomized studies exclude high-risk patients, including those with preexisting cardiovascular disease. “It is not clear what the appropriate transfusion trigger should be in these clinical settings.”

This study found anemia was strongly related to adverse outcomes and mortality at a nadir hemoglobin level much higher than that reported in other trials, Dr. Hawn noted. But in this study, it was difficult to differentiate between patients who received blood at a higher transfusion trigger because of active bleeding and those who were asymptomatic and their hemoglobin drifted down after surgery, she said. “I believe patient management and transfusion triggers would be quite different for actively bleeding patients or those suffering major intraoperative blood loss.”

Dr. Kougias’s team has launched a multicenter randomized trial, the TOP (Transfusion Trigger After Operations in High Cardiac Risk Patients) trial. They plan to enroll 1,520 patients who have high cardiac risk and compare transfusion thresholds of 7 and 10 g/dL. With about one-fifth of the enrollment goal achieved to date, the investigators expect the trial to be completed by the end of 2022.

Researchers who were not involved with the study stressed the need to treat anemia preoperatively whenever possible and prevent anemia during surgery to avoid transfusions when possible.

“The decision to transfuse a patient should always be based on when the risks of anemia outweigh the risks of transfusion. Current practice and research should be focused on prevention or avoidance of perioperative anemia so that transfusion can be circumvented,” said C. David Mazer, MD, a professor of anesthesia at St. Michael’s Hospital, University of Toronto.

Dr. Mazer led a randomized controlled trial, published in 2018, that showed in patients undergoing cardiac surgery who were at moderate to high risk for death, a restrictive strategy for red cell transfusion (<7.5 g/dL) intraoperatively or postoperatively was noninferior to a liberal strategy (9.5 g/dL) with regard to death from any cause, myocardial infarction, stroke or new-onset renal failure. This persisted up to six months after surgery (N Engl J Med 2018;379[13]:1224-1233).

Toby Richards, MD, a professor of vascular surgery at the University of Western Australia in Crawley, called for all surgical patients to be tested for anemia preoperatively. “Before we proceed into an operation, we need to stop and ensure the patient is as fit as possible. This includes managing and preventing anemia before pushing ahead to do the operation.”