article147

CYTO-PV

"Hematocrit Targeting in Polycythemia Vera". The New England Journal of Medicine. 2012.

Clinical Question

In patients with JAK2-positive polycythemia vera, does maintaining a hematocrit below 45% reduce the risk of cardiovascular death and major thrombosis compared to a higher hematocrit target?

Bottom Line

In patients with JAK2-positive polycythemia vera, maintaining a hematocrit target below 45% results in a significantly lower rate of cardiovascular death and major thrombosis compared to a target of 45 to 50%.

Major Points

Guidelines

Based on this study's findings, it is recommended that the hematocrit be maintained below 45% in patients with polycythemia vera to reduce the risk of cardiovascular death and major thrombotic events.

Design

- Multicenter, prospective, randomized, open-label clinical trial
- N=365 adults with JAK2-positive polycythemia vera
- Low-hematocrit group (n=182) with a hematocrit target of less than 45%
- High-hematocrit group (n=183) with a hematocrit target of 45 to 50%
- Median follow-up: 31 months

Population

- Inclusion Criteria: Adults with JAK2-positive polycythemia vera, per WHO 2008 diagnostic criteria
- Exclusion Criteria: Significant liver or renal disease, substance/alcohol abuse, pregnancy, life-threatening conditions, history of adverse reactions to hydroxyurea
- Baseline demographics were well-balanced between groups

Interventions

- Patients were assigned to receive phlebotomy, hydroxyurea, or both for targeted hematocrit management.

Outcomes

- Primary outcome: Time until death from cardiovascular causes or a major thrombotic event
- Secondary outcome: Total rate of cardiovascular events
- Additional outcomes: Incidence of cancer, progression to myelofibrosis, myelodysplasia, leukemic transformation, and hemorrhage
- Primary outcome observed in 2.7% of the low-hematocrit group vs. 9.8% of the high-hematocrit group (hazard ratio 3.91; P=0.007)
- No significant difference in adverse events between groups

Criticisms

- Although halted before the planned endpoint due to recruitment challenges, the study results provided unexpected evidence for the benefit of intensive hematocrit reduction.

Funding

Funded by the Italian Medicines Agency (AIFA) and Associazione Italiana per la Ricerca sul Cancro–Gruppo Italiano Malattie Mieloproliferative (AIRC-GIMEMA).