Hydroxyurea

A prospective randomized trial included 382 patients aged 40 to 59 years with ET and without high-risk factors (no history of thrombosis or bleeding, no hypertension, no diabetes, platelet count ≤1,500 × 109/L). Patients were randomly assigned to receive aspirin alone or hydroxyurea plus aspirin.[28]

A prospective randomized trial included 382 patients aged 40 to 59 years with ET and without high-risk factors (no history of thrombosis or bleeding, no hypertension, no diabetes, platelet count ≤1,500 × 109/L). Patients were randomly assigned to receive aspirin alone or hydroxyurea plus aspirin.[28]

After a median follow-up of 73 months, there was no difference in thrombosis, hemorrhage, or survival (HR, 0.98; 95% CI, 0.42‒2.25; P = 1.0).[28][Level of evidence B1] Patients younger than 60 years who lacked high-risk factors did not benefit from the addition of hydroxyurea to aspirin.

A randomized trial of patients with ET and a high risk of thrombosis compared treatment with hydroxyurea titrated to attain a platelet count below 600 × 109/L with a control group that received no therapy. Hydroxyurea was found to be effective in preventing thrombotic episodes (4% vs. 24%).[13][Level of evidence B3]

A randomized trial of patients with ET and a high risk of thrombosis compared treatment with hydroxyurea titrated to attain a platelet count below 600 × 109/L with a control group that received no therapy. Hydroxyurea was found to be effective in preventing thrombotic episodes (4% vs. 24%).[13][Level of evidence B3]

A retrospective analysis of this trial found that antiplatelet drugs had no significant influence on the outcome. Resistance to hydroxyurea was defined as (1) a platelet count of greater than 600 × 109/L after 3 months of at least 2 g per day of hydroxyurea or (2) a platelet count greater than 400 × 109/L and a white blood cell count of less than 2.5 × 109/L or a hemoglobin less than 10 g/dL at any dose of hydroxyurea.[29]

A prospective randomized trial in the United Kingdom of 809 patients compared hydroxyurea plus aspirin with anagrelide plus aspirin.[30]

A prospective randomized trial in the United Kingdom of 809 patients compared hydroxyurea plus aspirin with anagrelide plus aspirin.[30]

Although the platelet-lowering effect was equivalent, the anagrelide group had significantly more thrombotic and hemorrhagic events (HR, 1.57; P = .03) and more myelofibrosis (HR, 2.92; P = .01).

A prospective randomized trial in the United Kingdom of 809 patients compared hydroxyurea plus aspirin with anagrelide plus aspirin.[30]

No differences were seen for subsequent myelodysplasia or acute leukemia in this trial.[27][Level of evidence B1]

Another prospective randomized trial also compared hydroxyurea with anagrelide in 259 previously untreated and high-risk patients.[31] In this central European trial, the diagnosis of ET was made by the WHO recommendations, not by the Polycythemia Vera Study Group criteria as in the U.K. study. This means that patients with leukocytosis and a diagnosis of early prefibrotic myelofibrosis (both groups with much higher rates of thrombosis) were excluded from the central European trial.

Another prospective randomized trial also compared hydroxyurea with anagrelide in 259 previously untreated and high-risk patients.[31] In this central European trial, the diagnosis of ET was made by the WHO recommendations, not by the Polycythemia Vera Study Group criteria as in the U.K. study. This means that patients with leukocytosis and a diagnosis of early prefibrotic myelofibrosis (both groups with much higher rates of thrombosis) were excluded from the central European trial.

In this analysis, there were no differences in outcome for thrombotic or hemorrhagic events.[31][Level of evidence B1]