Hydroxyurea vs. anagrelide in high-risk essential thrombocythemia
Trial question
What is the role of hydroxyurea in patients with essential thrombocythemia?
Study design
Multi-center
Open label
RCT
Population
Characteristics of study participants
58.0% female
42.0% male
N = 809
809 patients (467 female, 342 male).
Inclusion criteria: patients with essential thrombocythemia who were at high-risk for vascular events and already receiving low-dose aspirin.
Key exclusion criteria: myelodysplasia or myelofibrosis, and known causes of reactive thrombocytosis, MI within the previous three months, severe congestive HF, severe ventricular arrhythmia, pregnancy or lactation, or leg ulceration.
Interventions
N=401 hydroxyurea (at a starting dose of 0.5-1.0 g daily, subsequent adjustment to maintain platelet count < 400,000 per m³ plus aspirin 75-100 mg daily).
N=405 anagrelide (starting dose of 0.5 mg BID, subsequent adjustment to maintain platelet count < 400,000 per m³ plus aspirin 75-100 mg daily).
Primary outcome
Arterial or venous thrombosis, serious hemorrhage, or death from vascular causes
36
55
55.0
41.3
27.5
13.8
0.0
Hydroxyurea
Anagrelide
Significant
increase ▲
Significant increase in arterial or venous thrombosis, serious hemorrhage, or death from vascular causes (36 vs. 55; OR 1.57, 95% CI 1.04 to 2.37).
Secondary outcomes
Significant increase in arterial thrombosis (17 vs. 37; OR 2.16, 95% CI 1.27 to 3.69).
Significant increase in serious hemorrhage (8 vs. 22; OR 2.61, 95% CI 1.27 to 5.33).
Significant increase in transformation to myelofibrosis (5 vs. 16; OR 2.92, 95% CI 1.24 to 6.86).
Safety outcomes
Significant differences in study drug withdrawal due to side-effects (43 vs. 88, p < 0.001).
Conclusion
In patients with essential thrombocythemia who were at high-risk for vascular events and already receiving low-dose aspirin, hydroxyurea was superior to anagrelide with respect to arterial or venous thrombosis, serious hemorrhage, or death from vascular causes.
Reference
Harrison CN, Campbell PJ, Buck G et al. Hydroxyurea compared with anagrelide in high-risk essential thrombocythemia. N Engl J Med. 2005 Jul 7;353(1):33-45.
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