Anemia tied to worse acute coronary syndrome outcomes.

VIENNA -- Anemia was a significant risk factor for worse outcomes in patients with acute coronary syndrome in a post hoc analysis of almost 14,000 patients enrolled in a recent trial.

Despite this evidence of anemia's risk, it's premature to conclude that treating anemia--either with blood transfusions or with erythropoietin--is the best way to reduce the risk, Dr. Roxana Mehran said at the annual congress of the European Society of Cardiology.

"We believe that anemia is another risk factor, like age or diabetes, but there may be confounders when you find anemia in ACS [acute coronary syndrome] patients, so it's hard to tease out. It's a very difficult analysis, and we don't feel that we have figured out the anemia problem," said Dr. Mehran, director of outcomes research at the center for interventional vascular therapy at Columbia University, New York.

"Transfusions may have their own bad karma [in ACS patients]; they may have an independent association with death and other adverse outcomes." And the results of the new analysis also provide no evidence to support treatment with erythropoietin to relieve anemia in ACS patients. "Any time you suggest treatment, you need to assess its risks and benefits in a prospective, controlled trial," she said.

The effects of anemia in ACS were studied using data collected on 13,819 patients with either unstable angina or non-ST elevation myocardial infarction enrolled in the ACUITY (Acute Catheterization and Urgent Intervention Triage Strategy) trial. The primary end point of the study showed that benefit and risk from treatment with the antithrombotic drug bivalirudin (Angiomax) alone were similar to standard treatment with a heparin (either unfractionated heparin or low-molecular-weight heparin) plus a glycoprotein IIb/IIIa inhibitor, or to treatment with bivalirudin plus a GP IIb/IIIa inhibitor (N. Engl. J. Med. 2006;355:2203-16). More specifically, treatment with bivalirudin alone was linked with a similar rate of ischemic events but a significantly lower rate of major bleeding episodes than in the heparin plus GP IIb/IIIa group.

The trial was sponsored by the Medicines Co., which markets Angiomax. Dr. Mehran is a speaker for and had received honoraria from the Medicines Co.

Anemia information at baseline was available for about 94% of patients, including 10,839 without anemia and 2,200 with anemia. Anemia was defined by World Health Organization criteria: Women were diagnosed if their hemoglobin level was less than 12 g/dL, and men had anemia if their hemoglobin level was less than 13 g/dL. The patients in the study with anemia had significantly higher levels of comorbidities, including diabetes, hypertension, and a history of myocardial infarction.

The primary end point in the ACUITY trial was a composite risk and benefit measure for the first 30 days after treatment that added the total number of deaths, myocardial infarctions, unplanned revascularization procedures, and major bleeding events. For the patients with anemia, the rate was 16.2%, compared with a 10.2% rate in the nonanemic patients, a statistically significant difference, Dr. Mehran said. Anemia was linked with significantly worse outcomes for each of these outcome measures, except for the rate of unplanned revascularization. (See box.)

The worse outcomes of patients with anemia were also seen uniformly, regardless of how the ACS patients were managed: with percutaneous coronary intervention (56%), coronary bypass surgery (11%), or medical management only (33%).

This analysis has the major limitation of trying to determine which patients had anemia at baseline and which did not, amid a high incidence of bleeding and treatment with transfusions.

Despite a reliance on the WHO criteria, "defining anemia was extremely subjective" in these patients, Dr. Mehran said. 30-Day Outcomes in Acute Coronary Syndrome

Anemia at No anemia at

baseline baseline

(n = 2,200) (n = 10,839) Death 2.7% 1.2%* Unplanned revascularization 2.6% 2.4% Nonfatal myocardial infarction 6.0% 4.9%* Major bleeds 8.8% 3.9%* Overall rate of clinical events 16.4% 10.3%* *Statistically significant. Source: Dr. Mehran ELSEVIER GLOBAL MEDICAL NEWS Note: Table made from bar graph.