Summary of findings 4. Long‐term red cell transfusion versus hydroxyurea and phlebotomy in people who are at risk of a secondary stroke who have had previous long‐term red cell transfusions.
| Secondary prevention | ||||||
| Patient or population: individuals with sickle cell disease who have had a stroke who have had long‐term red cell transfusions to prevent another stroke Setting: outpatients Intervention: blood transfusion with iron chelation Comparison: hydroxyurea with phlebotomy | ||||||
| Outcomes | Anticipated absolute effects* (95% CI) | Relative effect (95% CI) | № of participants (trials) | Quality of the evidence (GRADE) | Comments | |
| Risk with hydroxyurea and phlebotomy | Risk with Blood transfusion | |||||
| Clinical stroke assessed with: no previous red cell transfusion follow‐up: mean 24 months | Trial population | RR 14.78 (0.86 to 253.66) | 133 (1 RCT) |
⊕⊝⊝⊝ Very low 1 2 3 | ||
| 0 per 1000 |
0 per 1000 (0 to 0) |
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| All‐cause mortality | 15 per 1000 |
15 per 1000 (1 to 198) |
Peto OR 0.98 (0.06 to 15.92) |
133 (1 RCT) |
⊕⊝⊝⊝ Very low 1 2 3 | |
| Transfusion‐related adverse events ‐ assessed with liver iron concentration mg Fe/g dry weight liver |
Hydroxyurea arm: median 17.2 mg IQR 10.0 to 30.6 Transfusion arm: median 17.3 mg IQR 8.8 to 30.7 |
56 (1 RCT) |
⊕⊕⊝⊝ Low 1 2 | P = 0.7920a Switching to hydroxyurea and phlebotomy may reduce serum ferritin levels compared to continuing to receive red cell transfusions and chelation 1994 μg/L, interquartile range (IQR) 998 to 3475, in the hydroxyurea arm and 4064 μg/L, IQR 2330 to 7126, in the transfusion arm; one trial, 133 participants; P < 0.001 a |
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| Incidence of TIA | Trial population | RR 0.66 (0.25 to 1.74) | 133 (1 RCT) |
⊕⊝⊝⊝ Very low 1 2 3 | ||
| 136 per 1000 |
90 per 1000 (34 to 237) |
|||||
| Serious adverse events as a result of sickle cell‐related complications assessed with: ACS | Trial population |
RR 0.33 (0.04 to 3.08) |
133 (1 RCT) |
⊕⊝⊝⊝ Very low1 2 3 | ||
| 45 per 1000 |
15 per 1000 (2 to 140) |
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| Measures of neurological impairment ‐ not reported | Outcome not reported | ‐ | ‐ | ‐ | ||
| Quality of life ‐ not reported | Outcome not reported | ‐ | ‐ | ‐ | ||
| *The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). Abbreviations: ACS: acute chest syndrome; CI: confidence interval; RR: risk ratio; OR: odds ratio; TIA: transient ischaemic attack | ||||||
| GRADE Working Group grades of evidence High quality: we are very confident that the true effect lies close to that of the estimate of the effect Moderate quality: we are moderately confident in the effect estimate: The true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different Low quality: our confidence in the effect estimate is limited: The true effect may be substantially different from the estimate of the effect Very low quality: we have very little confidence in the effect estimate: The true effect is likely to be substantially different from the estimate of effect | ||||||
1 We downgraded the quality of the evidence by 1 due to risk of bias. Trial was not blinded and stopped early
2 We downgraded the quality of the evidence by 1 due to indirectness. Only children with HbSS or HbSβº thalassaemia included in trials
3 We downgraded the quality of the evidence by 1 due to imprecision. The estimate has very wide CIs
a Analysis performed by the trial authors