Anagrelide: what was new in 2004 and 2005?

Anagrelide is an established platelet-reducing drug. Although there are gaps in the understanding of its mechanism of action, two randomized comparisons with other drugs used for therapy of patients with essential thrombocythemia (ET) have been performed. Recent progress has been made in this field with the development of better determination techniques, with the characterization of metabolites, and with studies of their mechanism of action on megakaryocytes and platelets. More data are now available from various noncomparative clinical trials on its clinical efficacy and safety. Only few investigations are available that document its long-term effects. Although the drug should not be used during pregnancy, there are a few studies that report that pregnant women have taken this drug without harm to the newborn. Studies have also investigated the effects of anagrelide on platelets, indicating that platelet function is as important as platelet counts in ET. Preliminary analyses of the mechanism of action of anagrelide have revealed that the drug interferes with the signal transduction of the thrombopoietin receptor. Results of the first phase III trial (PT1) that compared anagrelide/aspirin with hydroxyurea/aspirin have sparked an intense discussion, given that the combination of anagrelide and aspirin causes more bleeding complications in the gastrointestinal tract. It has been speculated that the higher number of transient ischemic attacks in this study arm is not caused by thrombotic events but by small bleedings that would be responsible for transient hemorrhagic attacks. More insights are expected from the recently completed ANAHYDRET trial that compared monotherapy with hydroxyurea and anagrelide.