A Multinational Trial of Prasugrel for Sickle Cell Vaso-Occlusive Events

Conner Mansfield, Mercer University College of Pharmacy

It is thought that almost every patient with sickle cell disease will experience a vaso-occlusive, or acute pain, crisis. Vaso-occlusive crises are considered to involve significant pain and the potential for progression to acute chest syndrome, which can lead to respiratory failure or death. Hydroxyurea appears to be the only medication used in long-term treatment that can prevent vaso-occlusive crises. Antiplatelet therapy is not currently a recommended treatment in the management of sickle cell disease. [1]

This study intended to determine whether or not antiplatelet therapy with prasugrel (Effient®) prevents vaso-occlusive crises from occurring.

A Multinational Trial of Prasugrel for Sickle Cell Vaso-Occlusive Events [2]
Design Doubled-blind, placebo-controlled trial; N= 341
Objective To assess the efficacy of prasugrel in reducing the rate of vaso-occlusive crisis
Study Groups Placebo or prasugrel 0.08 mg/kg (target range between 0.04 mg/kg to 0.12 mg/kg) by mouth once daily
Methods Patients were children two to 17 years of age who had sickle cell anemia or thalassemia and had experienced two or more vaso-occlusive crises during the previous year. They underwent a two week screening period and then were randomized to receive prasugrel or placebo for nine to 24 months. The prasugrel dose was titrated to a platelet reactivity of 231 to 136 P2Y12 reaction units within 45 days. Patients returned to clinic for follow-up every 3 months.
Duration Randomization occurred from May 2013 to June 2015.
Primary Outcome Measure The rate of vaso-occlusive crisis defined as painful crisis or acute chest syndrome
Baseline Characteristics   Placebo Group; n= 170 Prasugrel Group; n= 171
Mean Age—Years 10.6 10.6
Hydroxyurea Use (%) 76 (44.7) 77 (45.0)
Female Sex (%) 86 (50.6) 87 (50.9)
Mean Weight—kg 31.9 33.2
Black Race (%) 109/169 (64.5) 113 (66.1)
Mean Vaso-Occlusive Crises in Previous Year 4.0 3.5
Results   Placebo Group Prasugrel Group Rate Ratio p-value
Rate of Vaso-Occlusive Crises per Patient Year 2.77 2.30 0.83 0.12
Adverse Events Common Adverse Events: hemorrhagic events n= 32 (18.8%), non-hemorrhagic events 157 (92.4%)
Serious Adverse Events: hemorrhagic events n= 5 (2.9%), non-hemorrhagic events n= 87 (51.2%)
Percentage that Discontinued due to Adverse Events: n= 6 (3.5%)
Study Author Conclusions The rate of vaso-occlusive crises was not significantly lower with prasugrel than with placebo among children with sickle cell anemia, although the smaller number of vaso-occlusive crises in the prasugrel group, particularly among the older children, is encouraging.

This trial did not demonstrate that prasugrel can prevent vaso-occlusive crises in children with sickle cell disease. Subgroup analyses suggest that there might be a benefit in older pediatric patients. Further research is needed before prasugrel can be routinely used to prevent vaso-occlusive crises in sickle cell patients.


  1. Yawn BP, Buchanan GR, Afenyi-annan AN, et al. Management of sickle cell disease: summary of the 2014 evidence-based report by expert panel members. JAMA. 2014;312(10):1033-48.
  2. Heeney MM, Hoppe CC, Abboud MR, et al. A Multinational Trial of Prasugrel for Sickle Cell Vaso-Occlusive Events. N Engl J Med. 2015.

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