title: Cardiovascular events and intensity of treatment in polycythemia vera.
abstract: BACKGROUND
  Current treatment recommendations for patients with polycythemia vera call for maintaining a hematocrit of less than 45%, but this therapeutic strategy has not been tested in a randomized clinical trial.
  
  
  METHODS
  We randomly assigned 365 adults with JAK2-positive polycythemia vera who were being treated with phlebotomy, hydroxyurea, or both to receive either more intensive treatment (target hematocrit, <45%) (low-hematocrit group) or less intensive treatment (target hematocrit, 45 to 50%) (high-hematocrit group). The primary composite end point was the time until death from cardiovascular causes or major thrombotic events. The secondary end points were cardiovascular events, cardiovascular hospitalizations, incidence of cancer, progression to myelofibrosis, myelodysplasia or leukemic transformation, and hemorrhage. An intention-to-treat analysis was performed.
  
  
  RESULTS
  After a median follow-up of 31 months, the primary end point was recorded in 5 of 182 patients in the low-hematocrit group (2.7%) and 18 of 183 patients in the high-hematocrit group (9.8%) (hazard ratio in the high-hematocrit group, 3.91; 95% confidence interval [CI], 1.45 to 10.53; P=0.007). The primary end point plus superficial-vein thrombosis occurred in 4.4% of patients in the low-hematocrit group, as compared with 10.9% in the high-hematocrit group (hazard ratio, 2.69; 95% CI, 1.19 to 6.12; P=0.02). Progression to myelofibrosis, myelodysplasia or leukemic transformation, and bleeding were observed in 6, 2, and 2 patients, respectively, in the low-hematocrit group, as compared with 2, 1, and 5 patients, respectively, in the high-hematocrit group. There was no significant between-group difference in the rate of adverse events.
  
  
  CONCLUSIONS
  In patients with polycythemia vera, those with a hematocrit target of less than 45% had a significantly lower rate of cardiovascular death and major thrombosis than did those with a hematocrit target of 45 to 50%. (Funded by the Italian Medicines Agency and others; ClinicalTrials.gov number, NCT01645124, and EudraCT number, 2007-006694-91.).
authors.affiliation: Consorzio Mario Negri Sud, Santa Maria Imbaro, Italy. marchioli@negrisud.it
authors.forename: Roberto
authors.initials: R
authors.lastname: Marchioli
authors.forename: Guido
authors.initials: G
authors.lastname: Finazzi
authors.forename: Giorgina
authors.initials: G
authors.lastname: Specchia
authors.forename: Rossella
authors.initials: R
authors.lastname: Cacciola
authors.forename: Riccardo
authors.initials: R
authors.lastname: Cavazzina
authors.forename: Daniela
authors.initials: D
authors.lastname: Cilloni
authors.forename: Valerio
authors.initials: V
authors.lastname: De Stefano
authors.forename: Elena
authors.initials: E
authors.lastname: Elli
authors.forename: Alessandra
authors.initials: A
authors.lastname: Iurlo
authors.forename: Roberto
authors.initials: R
authors.lastname: Latagliata
authors.forename: Francesca
authors.initials: F
authors.lastname: Lunghi
authors.forename: Monia
authors.initials: M
authors.lastname: Lunghi
authors.forename: Rosa Maria
authors.initials: RM
authors.lastname: Marfisi
authors.forename: Pellegrino
authors.initials: P
authors.lastname: Musto
authors.forename: Arianna
authors.initials: A
authors.lastname: Masciulli
authors.forename: Caterina
authors.initials: C
authors.lastname: Musolino
authors.forename: Nicola
authors.initials: N
authors.lastname: Cascavilla
authors.forename: Giovanni
authors.initials: G
authors.lastname: Quarta
authors.forename: Maria Luigia
authors.initials: ML
authors.lastname: Randi
authors.forename: Davide
authors.initials: D
authors.lastname: Rapezzi
authors.forename: Marco
authors.initials: M
authors.lastname: Ruggeri
authors.forename: Elisa
authors.initials: E
authors.lastname: Rumi
authors.forename: Anna Rita
authors.initials: AR
authors.lastname: Scortechini
authors.forename: Simone
authors.initials: S
authors.lastname: Santini
authors.forename: Marco
authors.initials: M
authors.lastname: Scarano
authors.forename: Sergio
authors.initials: S
authors.lastname: Siragusa
authors.forename: Antonio
authors.initials: A
authors.lastname: Spadea
authors.forename: Alessia
authors.initials: A
authors.lastname: Tieghi
authors.forename: Emanuele
authors.initials: E
authors.lastname: Angelucci
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Visani
authors.forename: Alessandro Maria
authors.initials: AM
authors.lastname: Vannucchi
authors.forename: Tiziano
authors.initials: T
authors.lastname: Barbui
mesh_terms: D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002318:Cardiovascular Diseases / Q000209:etiology / Q000401:mortality*; D003131:Combined Modality Therapy; D005260:Female; D005500:Follow-Up Studies; D006400:Hematocrit; D006801:Humans; D006918:Hydroxyurea / Q000627:therapeutic use*; D053614:Janus Kinase 2; D008297:Male; D008875:Middle Aged; D018962:Phlebotomy; D011087:Polycythemia Vera / Q000097:blood / Q000150:complications / Q000628:therapy*; D013927:Thrombosis / Q000453:epidemiology / Q000209:etiology*
chemical_list: D000970:Antineoplastic Agents; D053614:Janus Kinase 2; D006918:Hydroxyurea