Hydroxyurea may reduce stroke risk in sickle cell disease children
Researchers reviewed dats from 13 clinical trials to assess medicine's efficacy
Hydroxyurea may effectively reduce the risk of stroke in children with sickle cell disease (SCD), a systematic review has found.
“This review highlights the need for further research to understand the real-world feasibility and practical implications of hydroxyurea dosing strategies and to explore its long-term safety and efficacy in primary stroke prevention,” the researchers wrote.
The study, “Hydroxyurea to Decrease Stroke Risk in Children with Sickle Cell Anemia: A Systematic Review and Meta-analysis,” was published in Blood Global Hematology.
In SCD, an abnormal form of the protein that carries oxygen inside red blood cells, called hemoglobin, clumps together and causes cells to acquire a sickle-like shape. These cells tend to die prematurely, which leads to anemia, and they can become stuck inside blood vessels, blocking blood flow and triggering painful vaso-occlusive crises (VOCs) and other complications.
People with SCD are at a higher risk of stroke, particularly children. This is because sickled red blood cells can obstruct vessels and cause them to become narrower over time to the point that some brain regions may not receive enough oxygen and nutrients, and become damaged.
The risk for stroke increases as cerebral blood flow velocity rises, which can be measured by transcranial doppler ultrasound (TCD). Studies indicate that for every increase of 10 cm/second (s) above 170 cm/s, stroke risk increases by 30%.
Chronic blood transfusions can decrease patients’ risk of stroke, they aren’t always feasible in low-income countries. Hydroxyurea, which is more accessible and affordable, is increasingly being used as an alternative strategy.
An ‘effective strategy’
However, “there is still no consensus on the use of hydroxyurea in children with high stroke risk, leading to variability in treatment practices,” wrote a team led by researchers in Tanzania who reviewed data on the efficacy of hydroxyurea in reducing stroke risk in children with sickle cell anemia, the most common and severe form of SCD. Thirteen clinical trials detailed in more than 100 publications were included in the analysis.
The trials were conducted in seven countries, the U.S., U.K., Jamaica, Dominican Republic, Brazil, Nigeria, and Tanzania. Most were open-label, meaning the participants were aware of the treatment they were receiving. Four were randomized controlled trials where participants were randomly assigned to different treatment regimens that included different dosing schedules of hydroxyurea, a placebo, or to remain in observation.
The selected trials enrolled 592 children ranging in age from 6 months to 18 years. From these, 575 were treated with hydroxyurea and received an average dose that ranged from 10.8 to 27.9 mg/kg/day, for a mean of 1.6 years.
To assess the primary risk for stroke, the participants underwent TCD before and during treatment with hydroxyurea. In nearly all the trials, hydroxyurea decreased TCD velocities by a mean of 30 cm/s, normalizing it in most children (64.9%, on average). The largest reductions were seen in two trials that enrolled only children with abnormal TCD velocities that exceeded 200 cm/s.
Significant reductions were seen as early as three months after treatment started and lasted for up to five years, with a continuous decline over the first year of treatment.
Most trials reported no strokes among children treated with hydroxyurea, although three reported strokes in children with a baseline TCD above 200 cm/s. Following hydroxyurea treatment, hemoglobin levels increased by 1 to 2 g/dL in most trials.
The researchers called hydroxyurea “an effective strategy for reducing TCD velocities and stroke risk in children with [SCD] and … a feasible alternative when transfusions are unavailable, especially in resource-limited settings.”
“Additional research is needed to clarify effect on stroke incidence and optimal dosing strategies for durable treatment effect, long-term safety, and comprehensive benefits in diverse healthcare settings,” they wrote.
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