Platelet inhibitor prasugrel has failed to show a significant reduction in the rate of vaso-occlusive crises events in children and adolescents with sickle cell anemia, according to data presented Dec. 8 at the annual meeting of the American Society of Hematology.
The phase III randomized placebo-controlled trial of 341 children and adolescents (aged 2-17 years), known as the Determining Effects of Platelet Inhibition on Vaso-Occlusive Events (DOVE) trial – simultaneously published in the New England Journal of Medicine – showed the rate of vaso-occlusive crises was 2.30 per person-year in the prasugrel group and 2.77 in the placebo group (rate ratio 0.83, 95% confidence interval 0.66-1.05, P = 0.12), with a slightly greater but still nonsignificant reduction among the older patients aged 12-17 years.
Courtesy Wikimedia Commons/Osaro Erhabor/Creative Commons License
Treatment with prasugrel did not achieve any significant reductions in secondary outcomes of hospitalizations for vaso-occlusive crises, red-cell transfusions, pain rate or intensity, analgesic use, or school absences, compared with placebo. Platelet reactivity, however, was significantly lower in the prasugrel group (N Engl J Med. 2015, Dec 8. doi: 10.1056/NEJMoa1512021).
“Sickle cell anemia is a heterogeneous and complex disease in which platelet activation is only one of several mechanisms of vascular injury, which perhaps explains why prasugrel was ineffective,” wrote Dr. Matthew M. Heeney of Dana-Farber/Boston Children’s Cancer and Blood Disorders Center, and his coauthors.
“However, the nonsignificant effect of prasugrel in the oldest age group may suggest that platelet activation is relatively more important in these older patients, a hypothesis that is consistent with the fact that endothelial dysfunction in sickle cell disease is progressive.”
Daiichi Sankyo and Eli Lilly funded the study. Several authors disclosed ties with Eli Lilly or other pharmaceutical companies. Three authors were employees of Eli Lilly, and one was an employee of Daiichi Sankyo.