A large-scale trial testing the intensity of CYTOreductive therapy to prevent cardiovascular events In patients with Polycythemia Vera (PV)

To assess the benefit/risk profile of cytoreductive therapy, plus low-dose aspirin when not contraindicated, with phlebotomy and/or hydroxyurea (HU, oral administration) aimed at maintaining hematocrit (HCT) < 45% Vs. maintaining HCT in the range of 45-50% in patients with PV treated at the best of recommended therapies (e.g., low dose of aspirin when indicated and adequate control of standard cardiovascular risk factors).To demonstrate that maintaining HCT < 45% (either with phlebotomy or HidroxyUrea (HU) (standard cytoreduction) is more effective than maintaining HCT in the range of 45-50% (either with phlebotomy or HU) (experimental cytoreduction) in the reduction of CV deaths plus thrombotic events (stroke, acute coronary syndrome [ACS], transient ischemic attack [TIA], pulmonary embolism [PE], splanchnic thrombosis, deep vein thrombosis [DVT], and any other clinically relevant thrombotic event). All patients will be treated with phlebotomy and/or HU with the goal to reach and maintain the target HCT established by randomization. Phlebotomy should be performed initially by removing 250-500 ml of every other day or twice a week until the target HCT is obtained. HU should be administered initially at a dose of 0.5-1.0 g daily. The patient is followed with weekly blood counts adjusting dose to achieve a platelet count < 400,000/mmc. If neutropenia occurs, the dose of HU should be lowered so as not to reduce leukocyte < 3,500/mmc. Blood counts at regular intervals (monthly) will establish the frequency of future phlebotomies with the goal to maintain the target HCT. Supplemental iron therapy should not be given. LENGTH OF STUDY: 5 years