ANAHYDRET
Trial question
Is anagrelide noninferior to hydroxyurea in patients with essential thrombocythemia?
Study design
Multi-center
Single blinded
RCT
Population
Characteristics of study participants
64.0% female
36.0% male
N = 259
259 patients (165 female, 93 male)
Inclusion criteria: patients with essential thrombocythemia who have high-risk profile
Key exclusion criteria: pregnancy, contraindications to the study drugs, known lactose intolerance, severe renal disease, severe liver disease, coexisting malignancy, or systemic diseases
Interventions
N=122 anagrelide (started at a dose of 1.0 mg/day during the first week and adjusted until maintenance of the platelet count at normal or close to normal levels)
N=137 hydroxyurea (started at a dose of 1,500 mg/day and adjusted until maintenance of the platelet count at normal or close to normal levels)
Primary outcome
ET-related major and minor thrombohemorrhagic events at 6 months
22
29
29.0 events
21.8 events
14.5 events
7.3 events
0.0 events
Anagrelide
Hydroxyurea
Difference not exceeding
nonferiority margin ✓
Difference not exceeding nonferiority margin in ET-related major and minor thrombohemorrhagic events at 6 months (22 events vs. 29 events; HR 1.19, 95% CI 0.61 to 2.3)
Secondary outcomes
No significant difference in ET-related major and minor thrombohemorrhagic events at 12 months (33 events vs. 31 events; HR 1.03, 95% CI 0.57 to 1.81)
No significant difference in ET-related events, after 36 months (51 events vs. 47 events; HR 0.92, 95% CI 0.57 to 1.46)
No significant difference in the rate of no ET-related thrombotic or bleeding events after observation of up to 6 years (63.9% vs. 67.4%; HR 0.92, 95% CI 0.57 to 1.5)
Safety outcomes
No significant difference in adverse events and adverse events leading to discontinuation of drugs.
Significant differences in anemia (9.0% vs. 18.3%), leukopenia (0.8% vs. 28.2%), palpitations (24.6% vs. 2.3%).
Conclusion
In patients with essential thrombocythemia who have high-risk profile, anagrelide was noninferior to hydroxyurea with respect to a ET-related major and minor thrombohemorrhagic events at 6 months.
Reference
Gisslinger H, Gotic M, Holowiecki J et al. Anagrelide compared with hydroxyurea in WHO-classified essential thrombocythemia: the ANAHYDRET Study, a randomized controlled trial. Blood. 2013 Mar 7;121(10):1720-8.
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