Hydroxyurea compared with anagrelide in high-risk essential thrombocythemia.
BACKGROUND
We conducted a randomized comparison of hydroxyurea with anagrelide in the treatment of essential thrombocythemia.


METHODS
A total of 809 patients with essential thrombocythemia who were at high risk for vascular events received low-dose aspirin plus either anagrelide or hydroxyurea. The composite primary end point was the actuarial risk of arterial thrombosis (myocardial infarction, unstable angina, cerebrovascular accident, transient ischemic attack, or peripheral arterial thrombosis), venous thrombosis (deep-vein thrombosis, splanchnic-vein thrombosis, or pulmonary embolism), serious hemorrhage, or death from thrombotic or hemorrhagic causes.


RESULTS
After a median follow-up of 39 months, patients in the anagrelide group were significantly more likely than those in the hydroxyurea group to have reached the primary end point (odds ratio, 1.57; 95 percent confidence interval, 1.04 to 2.37; P=0.03). As compared with hydroxyurea plus aspirin, anagrelide plus aspirin was associated with increased rates of arterial thrombosis (P=0.004), serious hemorrhage (P=0.008), and transformation to myelofibrosis (P=0.01) but with a decreased rate of venous thromboembolism (P=0.006). Patients receiving anagrelide were more likely to withdraw from their assigned treatment (P<0.001). Equivalent long-term control of the platelet count was achieved in both groups.


CONCLUSIONS
Hydroxyurea plus low-dose aspirin is superior to anagrelide plus low-dose aspirin for patients with essential thrombocythemia at high risk for vascular events.
Department of Haematology, University of Cambridge, and Addenbrooke's National Health Service Trust, Cambridge, United Kingdom.
Claire N
CN
Harrison
Peter J
PJ
Campbell
Georgina
G
Buck
Keith
K
Wheatley
Clare L
CL
East
David
D
Bareford
Bridget S
BS
Wilkins
Jon D
JD
van der Walt
John T
JT
Reilly
Andrew P
AP
Grigg
Paul
P
Revell
Barrie E
BE
Woodcock
Anthony R
AR
Green
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001241:Aspirin / Q000008:administration & dosage*; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D006470:Hemorrhage / Q000209:etiology / Q000401:mortality; D006801:Humans; D006918:Hydroxyurea / Q000009:adverse effects / Q000627:therapeutic use*; D015470:Leukemia, Myeloid, Acute / Q000209:etiology; D008297:Male; D008875:Middle Aged; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D010976:Platelet Count; D055728:Primary Myelofibrosis / Q000209:etiology / Q000517:prevention & control; D011799:Quinazolines / Q000009:adverse effects / Q000627:therapeutic use*; D013920:Thrombocythemia, Essential / Q000150:complications / Q000188:drug therapy* / Q000401:mortality; D013927:Thrombosis / Q000209:etiology / Q000401:mortality
D000970:Antineoplastic Agents; D010975:Platelet Aggregation Inhibitors; D011799:Quinazolines; C021139:anagrelide; D001241:Aspirin; D006918:Hydroxyurea