Study highlights:

- Risks of an anemia drug appear to outweigh its benefits among diabetic patients with kidney disease, anemia and a history of cardiovascular disease or stroke.

- This first large, randomized, placebo-controlled trial finds drug raises hemoglobin levels and reverses anemia but does not improve patient cardiovascular outcomes.

- Treatment with darbepoetin alfa in patients with type 2 diabetes, chronic kidney disease and moderate anemia doubled the risk of stroke compared to placebo.

ORLANDO, Fla., Nov. 16 /PRNewswire-USNewswire/ -- Risks from a drug used to correct anemia outweighed its benefits in type 2 diabetic patients with kidney disease and anemia, according to results of the first large, placebo-controlled study of the agent reported in a late-breaking clinical trial at the American Heart Association's Scientific Sessions 2009.

Earlier results of the Trial to Reduce Cardiovascular Events With Aranesp Therapy (TREAT), reported at a recent meeting of the American Society of Nephrology, showed that use of darbepoetin alfa to raise hemoglobin levels in patients with type 2 diabetes, chronic kidney disease (without dialysis) and moderate anemia (low red cell blood count) lessened the need for blood transfusions. Severe anemia is associated with an increased risk of cardiovascular and kidney events.

Researchers said they hoped by treating the anemia it would lessen the cardiovascular mortality and morbitity of patients. However, it failed to reduce the rate of the composite endpoint of death or cardiovascular events (nonfatal heart attack, congestive heart failure, stroke or hospitalization for myocardial ischemia). In addition, almost twice as many patients randomized to the darbepoetin had a stroke (5 percent versus 2.6 percent).

There were two subgroups: the nearly two-thirds of TREAT patients with prior cardiovascular disease and the 11.1 percent of patients with a history of stroke.

In a new analysis, reported at the American Heart Association Scientific Sessions, those stroke patients seemed particularly vulnerable to the adverse events when randomized to darbepoetin, said Marc A. Pfeffer, M.D., Ph.D., the study's principal investigator, the Dzau Professor of Medicine at Harvard and a senior physician in cardiovascular medicine at Brigham and Women's Hospital in Boston, Mass.

Researchers, who looked at a composite endpoint of cardiovascular events, found that 47 percent (109 of 231) of the stroke survivors taking darbepoetin alfa had a cardiac event or died, compared to 37 percent of the placebo group (79 of 216 subjects).

TREAT, started in 2004, was conducted in 24 countries in 4,038 patients, more than half women, average patient age 68.

Darbepoetin alfa belongs to a class of drugs called erythropoiesis-stimulating agents (ESAs) that have been used for more than a quarter century to fight anemia. ESAs effectively raise hemoglobin levels, the marker for anemia.

"This trial is an excellent example of why surrogate markers, such as increased hemoglobin levels, should not take the place of clinical outcomes data," Pfeffer said

"TREAT underscores the importance of placebo-controlled trials to assess risks as well as benefits. This new data will help physicians and patients make more informed decisions about the use of ESAS, and we believe for many that the risks will outweighs the benefits."

The research was supported and conducted in collaboration with Amgen.

Co-authors are: Emmanuel A. Burdmann, M.D., Ph.D.; Chao-Yin Chen, Ph.D.; Mark E. Cooper, M.D.; Dick de Zeeuw, M.D., Ph.D.; Kai-Uwe Eckardt, M.D.; Jan M. Feyzi, M.S.; Peter Ivanovich, M.D.; Reshma Kewalramani, M.D.; Andrew S. Levey, M.D.; Eldrin F. Lewis, M.D., M.P.H.; Janet B. McGill, M.D.; John J.V. McMurray, M.D.; Patrick Parfrey, M.D.; Hans-Henrik Parving, M.D.; Giuseppe Remuzzi, M.D.; Ajay K. Singh, M.D.; Scott D. Solomon, M.D.; and Robert Toto, M.D.

Disclosures: Dr. Pfeffer reports receiving consulting fees from Abbott, Amgen, AstraZeneca, Biogen, Boehringer Ingelheim, Boston Scientific, Bristol-Myers Squibb, Centocor, CVRx, Genentech, Cytokinetics, Daiichi Sankyo, Genzyme, Medtronic, Novartis, Roche, Sanofi-Aventis, Servier and VIA Pharmaceutics; grant support from Amgen, Baxter, Celladon, Novartis and Sanofi-Aventis; and being named co-inventor on a patent for the use of inhibitors of the renin-angiotensin system in selected survivors of myocardial infarction.

Statements and conclusions of study authors published in American Heart Association scientific meetings are solely those of the study authors and do not necessarily reflect the association's policy or position. The association makes no representation or guarantee as to their accuracy or reliability. The association receives funding primarily from individuals; foundations and corporations (including pharmaceutical, device manufacturers and other companies) also make donations and fund specific association programs and events. The association has strict policies to prevent these relationships from influencing the science content. Revenues from pharmaceutical and device corporations are available at www.americanheart.org/corporatefunding.

NR09 - 1165 (SS09/TREAT Pfeffer)

SOURCE American Heart Association

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