The role of hydroxyurea to prevent silent stroke in sickle cell disease: Systematic review and meta-analysis

BACKGROUND: Chronic blood transfusions are standard of care for stroke prevention in sickle cell disease but is not cost effective and not without risks. Hydroxyurea has emerged as an option in the prevention of silent stroke in sickle cell disease. OBJECTIVE: To evaluate the role of hydroxyurea in preventing silent strokes in a systematic review by adhering to the Cochrane guidelines. METHODS: PubMed, EMBASE, Web of Science Core Collection, and Cochrane Central Register of Controlled Trials were searched for the related articles. Eligibility criteria included randomized controlled trials (RCTs) comparing the use of hydroxyurea vs blood transfusions and observational studies evaluating the role of hydroxyurea to prevent stroke and silent stroke in patients with sickle cell anemia or sickle cell β thalassemia. The meta-analysis was conducted using STATA software version 13. RESULTS: We included 10 single arm observational studies with 361 participants, and one RCT study with 60 participants receiving hydroxyurea, respectively. There were no deaths attributed to hydroxyurea. The results revealed that 1% (95% CIs 0.0 to 0.05) of patients receiving hydroxyurea had stroke. 18% (95% CIs 0.03 to 0.4) of the hydroxyurea patients had silent stroke. 24% (95% CIs 0.02 to 0.57) of the hydroxyurea patients had adverse events attributed to hydroxyurea. CONCLUSION: Our findings suggest that hydroxyurea is safe and may prevent silent stroke and stroke in sickle cell disease. More high-quality studies including RCTs are needed.