Hydroxyurea more effective than anagrelide (Agrylin)
Should be first-line therapy for high-risk patients
The older drug hydroxyurea plus aspirin has shown to be more effective than the more expensive anagrelide (Agrylin) plus aspirin in treating patients with essential thrombocythemia at high risk for vascular events, according to a study published in the July 7 issue of the New England Journal of Medicine.
Hydroxyurea is widely used as first-line therapy for high-risk patients, often in combination with low-dose aspirin, the researchers say. However, there have been concerns about possible links between the use of hydroxyurea and an increased risk of leukemia. Anagrelide also has been used as first-line therapy for high-risk patients with essential thrombocythemia, although its efficacy has not previously been reported in a randomized trial.
In this study, researchers in 138 centers in the United Kingdom, Ireland, and Australia randomly assigned 404 patients to receive hydroxyurea plus aspirin and 405 to receive anagrelide plus aspirin. The composite primary endpoint was the actuarial risk of arterial thrombosis, venous thrombosis, serious hemorrhage, or death from thrombotic or hemorrhagic causes. Patients in both groups were followed for a median of 39 months.
Arterial thrombosis developed in more than twice as many patients in the anagrelide group as in the hydroxyurea group, the researchers say.
There were significantly more transient ischemic attacks in the anagrelide group than in the hydroxyurea group (14 vs. 1). The rates of myocardial infarction, unstable angina, and thrombotic stroke were higher in the anagrelide group but not significantly different from the rates in the hydroxyurea group. There also was a significant increase in the rate of serious hemorrhage in the anagrelide group, with gastrointestinal hemorrhage being particularly common.
The rate of venous thromboembolism in the anagrelide group was approximately one-fourth of that in the hydroxyurea group, however, and there was a significantly lower rate of deep-vein thrombosis in the anagrelide group. Pulmonary emboli developed in only seven patients, but five of the seven were in the hydroxyurea group. The rates of death from any cause and death from thrombotic or hemorrhagic causes were not significantly different between the two groups, although the study was not powered to detect any difference in mortality.
The increased risk of serious hemorrhage in the anagrelide plus aspirin group may reflect interference of anagrelide with platelet function in a way that synergizes with low-dose aspirin, the researchers say. "The results presented here suggest that if anagrelide is used, the decision whether to use concurrent aspirin therapy should depend on the relative risk of arterial thrombosis and hemorrhage in each patient."
Significantly more patients also withdrew from the anagrelide group because of side effects or because either an endpoint or a serious adverse event had developed. The lower rate of withdrawal from treatment with hydroxyurea still was evident even when analysis was restricted to patients who had not previously received hydroxyurea, the researchers say.
Overall, the results of this trial suggest that hydroxyurea plus aspirin should remain first-line therapy for patients with essential thrombocythemia at high risk for vascular events, they conclude.
An accompanying editorial agrees, calling the study a "well-designed and well-conducted trial."
"In summary, for now, hydroxyurea plus aspirin should be the standard of treatment for patients with essential thrombocythemia who are at high risk for thrombosis," wrote Tiziano Barbui, MD, and Guido Finassi, MD, of the division of hematology at Osperdali Riuniti in Bergamo, Italy.
The recent identification of an acquired mutation of the JAK2 gene in most patients with polycythemia vera and about one-half the patients with essential thrombocythemia or myelofibrosis may open a new avenue for treatment, they add. "New tyrosine kinase inhibitors are being developed with the aim of discovering targeted therapy for these diseases. We foresee clinical trials comparing tyrosine kinase inhibitors with standard therapy in the near future."
The older drug hydroxyurea plus aspirin has shown to be more effective than the more expensive anagrelide (Agrylin) plus aspirin in treating patients with essential thrombocythemia at high risk for vascular events, according to a study published in the July 7 issue of the New England Journal of Medicine.You have reached your article limit for the month. Subscribe now to access this article plus other member-only content.
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