A randomized clinical trial has confirmed that patients with polycythemia vera benefit from aggressive treatment to lower their hematocrit to less than 45 percent and maintain it at that level. The study was published online Dec. 8 in the New England Journal of Medicine. However, an editorial suggested the drugs should not be recommended for thrombosis prevention in patients with polycythemia vera.

Polycythemia vera is a rare abnormality of the bone marrow that results in overproduction of erythrocytes, granulocytes and platelets. According to study authors Roberto Marchioli, MD, of Consorzio Mario Negri Sud in Santa Maria Imbaro, Italy, and colleagues, treatment recommendations are based on limited data, primarily from observational trials, and individual clinical judgment. The primary treatment option at this time is phlebotomy with or without hydroxyurea to reduce hematocrit levels to 45 percent or less, but there is a lack of randomized clinical trial data to support these goals.

Marchioli et al conducted a large-scale multicenter, prospective, randomized CYTO-PV (Cytoreductive Therapy in Polycythemia Vera) trial in an attempt to establish whether aggressive treatment to control hematocrit levels leads to better outcomes than less intense treatment. Between May 2008 and February 2012, a total of 365 patients at multiple centers in Italy were randomized 1:1 into a low hematocrit group (target hematocrit of less than 45 percent) or a high hematocrit group (target hematocrit between 45 percent and 50 percent). All patients received phlebotomy, cytoreductive drugs or both, at the discretion of the treating physician, but the study protocol required that enrollees be brought to their target hematocrit level and maintained there.

The primary composite endpoint was time until death from cardiovascular causes or thrombotic events. The secondary endpoint was the total rate of cardiovascular events (primary endpoint plus superficial vein thrombosis).

The mean hematocrit at baseline was similar for both groups (47.2 percent for the low group and 47.5 percent for the high group). During the course of the study, the low group achieved and maintained a median hematocrit of 44.4 percent compared with 47.5 percent in the high hematocrit group.

After a median of 31 months of follow-up, 2.7 percent of patients in the low group reached the primary endpoint compared to 9.8 percent in the high group; this translates to an incidence of death from cardiovascular causes or major thrombosis of 1.1 per 100 person years in the low group and 4.4 per 100 person years in the high group.

In the editorial, Jerry L. Spivak, MD, of Johns Hopkins School of Medicine in Baltimore, lauded the study for resolving “a half century of debate about the role of phlebotomy in polycythemia vera.” However, he bemoaned the study’s failure to consider gender-based differences in risk, because “women normally have a lower red cell mass and hematocrit than men, and women with polycythemia vera are at risk for intra-abdominal venous thrombosis with an apparently normal hematocrit.”

Spivak noted that in accordance with current recommendations, patients within both the high and low groups were treated with aspirin and hydroxyurea, even though “neither drug has been shown to prevent venous or arterial thrombosis in such patients.” He pointed out that only the low hematocrit group demonstrated a reduced thrombosis rate, and surmised that the drugs had no role in reducing thrombosis. “In my opinion, neither drug should be routinely recommended for thrombosis prevention in patients with polycythemia vera,” he wrote.