6533b86cfe1ef96bd12c80e7

RESEARCH PRODUCT

Cardiovascular events and intensity of treatment in polycythemia vera.

R MarchioliG FinazziG SpecchiaR CacciolaR CavazzinaD CilloniV De StefanoE ElliA IurloR LatagliataF LunghiM LunghiRm MarfisiP MustoA MasciulliC MusolinoN CascavillaG QuartaM. L. RandiD RapezziM RuggeriE RumiAr ScortechiniS SantiniM ScaranoS SiragusaA SpadeaA TieghiE AngelucciG VisaniAm VannucchiBarbui T. Specchia GA MasciulliRm MarfisiR CavazzinaM ScaranoA D'amicoB FerriC GuidoL MarfisiC PeraA PolidoroR MarchioliM SaccoG LevantesiG TognoniG BarosiA CarobbioP LeoniAr ScortechiniS MulattieriS TomassettiE HonoratiG SpecchiaA RiccoF AlbanoD PastoreP CarluccioAm MazzoneAr RossiMc FinazziF DelainiA FalangaA RambaldiG QuartaG GuaragnaA GiannottaE AngelucciE UsalaMp SimulaF PiloR CacciolaE CacciolaF PezzellaE SeriaE Di FrancescoD RapezziA GallaminiL BertolottiAm VannucchiE AntonioliP GuglielmelliL PieriMc SusiniN BartalucciA BosiC MusolinoA D'angeloR CentorrinoD GeraceA AllegraA IurloA CortelezziC De PhilippisE FerrettiF CiceriS ClaudianiF LunghiS MalatoS TrincaEm PoglianiA BelottiE LanziEm ElliG GaidanoM LunghiC DeambrogiD RossiG SaglioD CilloniA RotoloC ZanoneI BertozziF TezzaV AneloniS SiragusaG QuintiniG SacculloC CaraccioloM CazzolaI CasettiC ElenaB LandiniE RumiG VisaniS BarulliB GuiducciM LucesoleL MalerbaA IsidoriS SantiniA GrossiM De StefanisC BiagioniA TieghiF MerliA ImovilliK CodeluppiS RubagottiN RomanoA BoniniE BellesiaP MustoMc MartorelliO VillaniE ZifaroneA ZonnoV SantopietroV De StefanoT ZaE RossiAm CiminelloS BettiG AlimenaR LatagliataA TafuriM BrecciaI CarmosinoA SpadeaF PisaniA RomanoM D'andreaN CascavillaM NobileFs MantuanoG RossiM TricaricoF RodeghieroM RuggeriF BedinL LissandriniS. Finotto

subject

MaleHematocritRECURRENT THROMBOSISlaw.inventionAged; Antineoplastic Agents; Cardiovascular Diseases; Combined Modality Therapy; Female; Follow-Up Studies; Humans; Hydroxyurea; Janus Kinase 2; Male; Middle Aged; Polycythemia Vera; Thrombosis; Hematocrit; Phlebotomy; Medicine (all)LEUKOCYTOSISPolycythemia veraRandomized controlled trialPhlebotomylawhemic and lymphatic diseasesESSENTIAL THROMBOCYTHEMIAClinical endpointHydroxyureaPolycythemia Vera Secondary ProphylaxisESSENTIAL THROMBOCYTHEMIA RECURRENT THROMBOSIS RISK-FACTOR HEMATOCRIT MANAGEMENT LEUKOCYTOSIS PREVENTION DIAGNOSIS EFFICACY WARFARINPolycythemia Veramedicine.diagnostic_testMedicine (all)Hazard ratioGeneral MedicineMiddle AgedCombined Modality TherapyHematocritCardiovascular DiseasesFemalemedicine.medical_specialtyrandomized trial; polycythemia veraAntineoplastic AgentsCardiovascular eventDIAGNOSISWARFARINRISK-FACTORInternal medicineMANAGEMENTmedicineHumansMyelofibrosisAdverse effectAgedbusiness.industryThrombosisPhlebotomyJanus Kinase 2EFFICACYmedicine.diseasePREVENTIONSurgeryPolycythemia Vera Cardiovascular event hematocritSettore MED/15 - MALATTIE DEL SANGUEbusinessFollow-Up Studies

description

A b s t r ac t 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 highhematocrit 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.)

http://hdl.handle.net/10447/96649