CHICAGO — American physicians are quick to order blood transfusions—and a growing body of evidence indicates that is not necessarily a good thing, Dr. Sunil V. Rao said at a satellite symposium held in conjunction with the annual meeting of the Society for Cardiovascular Angiography and Interventions.
“In the U.S., we're just very, very transfusion happy. We have a very quick transfusion trigger. And I think there are some compelling data in the acute coronary syndrome population that [suggest it] may not be such a good idea,” added Dr. Rao of Duke University Medical Center, Durham, N.C.
Indeed, his recent analysis of three large international clinical trials, totaling more than 24,000 acute coronary syndrome (ACS) patients in 30 countries, concluded that patients outside the United States were 76% less likely to get a blood transfusion. After adjusting for differences in baseline patient characteristics, procedures, and bleeding severity, non-U.S. ACS patients were still 24% less likely to get a transfusion than were comparable Americans.
The 10% of patients who received one or more blood transfusions during their hospitalization had an unadjusted 30-day mortality of 8%, significantly greater than the 3% rate in ACS patients who weren't transfused. After statistical adjustment for the transfused patients' greater age and more baseline comorbidities, transfusion was associated with a fourfold increased risk for mortality at 30 days.
In the setting of a nadir hematocrit of 25% or less, transfusion was beneficial. However, with a hematocrit above 25%, transfusion was associated with increased 30-day mortality (JAMA 2004;292:1555–62).
It is noteworthy that the adjusted odds ratio for 1-year mortality was also increased fourfold in transfused patients who underwent percutaneous coronary intervention in the Randomized Evaluation of PCI Linking Angiomax to Reduced Clinical Events (REPLACE-2) trial, most of whom had stable ischemic heart disease, Dr. Rao continued.
“That's close to what we found in our study of ACS patients. It suggests the effect may be real,” the cardiologist said at the symposium, sponsored by The Medicines Company.
Much the same appears to be true in patients without ischemic heart disease. A Cochrane Collaboration metaanalysis of 10 randomized clinical trials in which the majority of participants didn't have ischemic heart disease concluded that a restrictive transfusion strategy was associated with a 20% reduction in the relative risk of mortality, a 51% decrease in heart failure, and a 56% reduction in acute MI.
The notion that blood transfusion can be bad for patients in ways beyond the common concerns regarding disease transmission and acute immune reactions runs counter to conventional thinking. But packed RBCs possess several negative properties: They have a high affinity for oxygen and are severely depleted of nitric oxide, which plays an essential role in oxygen exchange.
In fact, packed RBCs function as nitric oxide sinks. They cause platelet aggregation and vasoconstriction. And in one study, administration of packed RBCs was associated with increased C-reactive protein and interleukin-6, important markers of inflammation.
If bleeding is bad for patients and transfusion often is, too, it's clear that the key is to prevent bleeding problems in the first place. Today the safety-efficacy equation has shifted such that a greater focus on safety will pay dividends in terms of efficacy. In contemporary practice, as shown in a recent 40,000-patient analysis from the CRUSADE National Quality Improvement Registry, the most common in-hospital adverse outcome in ACS patients is no longer ischemic complications but severe bleeding, Dr. Rao said.
Dr. Rao is a consultant to the Medicines Company, which funded ACUITY.