Anagrelide (
Agrylin, Xagrid) is an oral imidazoquinazoline agent which is indicated in Europe for the reduction of elevated platelet counts in at-risk patients with essential thrombocythaemia who are intolerant of or refractory to their current
therapy, and in the US for the reduction of elevated platelet counts and the amelioration of thrombohaemorrhagic events in patients with thrombocythaemia associated with
myeloproliferative disorders.
Anagrelide is well established as an effective platelet-lowering agent in most patients with essential thrombocythaemia, including both treatment-naive patients and those refractory to other cytoreductive
therapy. Results of the only randomised trial to date (the Primary Thrombocythaemia 1 [PT1] study) indicated that the composite primary endpoint (arterial or
venous thrombosis, serious haemorrhage or death from vascular causes) occurred more often in recipients of
anagrelide plus
aspirin than in those receiving hydroxycarbamide (
hydroxyurea) plus
aspirin. This trial also indicated that the incidence of the secondary endpoints transient ischaemic attack and gastrointestinal
bleeding favoured hydroxycarbamide plus
aspirin, while the incidence of
venous thrombosis favoured
anagrelide plus
aspirin. There were no differences between the groups in the incidence of secondary endpoints
myocardial infarction,
stroke,
unstable angina,
pulmonary embolism,
hepatic-vein thrombosis, other serious haemorrhage or related deaths. The design of the PT1 study has been queried with respect to the heterogeneous nature of the study population (possible inclusion of patients with early myelofibrotic disease) and the concomitant use of
aspirin (interaction with
anagrelide causing increased
bleeding events). Further data are therefore required before the role of
anagrelide in essential thrombocythaemia can be finalized. In the meantime, when considering treatment options for patients with this disorder,
anagrelide's positive effects on platelet function, lack of mutagenicity and lack of association with leukaemia or angiogenesis must be balanced against its comparative expense and positive inotropic effects. Thus, the role of
anagrelide in the management of high-risk patients with essential thrombocythaemia will ultimately depend on individual patient assessment and future clarification of the potential leukaemogenicity of hydroxycarbamide.