Observational studies evaluating frequency of acute clinical events in SCD*
| Authors/location . | Patient population/study design . | Genotype/inclusion criteria . | N . | Follow-up period mean/median (range) . | Clinical outcomes HU vs no HU† . | Comments . | ||||
|---|---|---|---|---|---|---|---|---|---|---|
| VOC . | ACS . | Transfusion . | Stroke . | Hospital use . | ||||||
| Ali et al, 2011/Jamaica | Children/retrospective | 42 SCA, 1 HbSC; neuroimaging documentation of stroke or dx of clinical stroke | 43 (HU: 10) | HU: 4.6 y; no HU:4.2 y | HU: (2/ 100 p-y); no HU or txn: (29/100 p-y) (HR 9.4, P = .03) | Chronic transfusion program was not available | ||||
| Gilmore et al, 2011/United Kingdom | Children and adults/retrospective | 61 SCA, 1 HbSD; majority-recurrent VOC; VOC with ACS | 62 (HU: 62) | 3 y (1-9) | ↓; P = .02 at 2 y | ↓; P = .0007 at 7 y | ↓; P = .002 at 7 y | Inpatient annual days; ↓; P < .001 at 7 y | Registry data | |
| Italia et al, 2008/India | Children and adults/prospective | 54 HbSS, 23 HbSβthal; Arab-Indian haplotype; 5+ VOC/y, 1 CVA in life, 2+ ACS/life, or (AVN of femur + any of the above | 77 (HU: 77) | 2 y | ↓ | ↓ | ↓ | ↓ | ↓ | High baseline HbF level; reduction in clinical events score stratified according to initial severity (P < .0001) |
| Lobo et al, 2013/Brazil | Children/retrospective | SCD; indications for HU: recurrent VOC; >1 ACS; Hb <6 g/dL, CVA | 1760 (HU: 267 [SCA: 243; HbSB+thal: 10; HbSC: 10; HbSD: 4]) | 7 y (3-17) HU: 2 y (0.1-6.5) | HU:1 no HU: 17 | HU: 0; no HU: 4 | ↓50% P < .001 | ↓ mortality; 1 in HU group; 37 in no-HU group | ||
| ED visits ↓35% P < .001 | ||||||||||
| Nzouakou et al, 2010/France | Adults and adolescents/retrospective | SCA; ≥3 VOC hospitalizations/y; recurrent ACS; recurrent priapism; switch from txn program | 123 (HU: 123) | 4.9 y (0.44-13.5) | ↓; P < .0001 | 15/31 pts stopped txn | ↓ (data on 64 pts); P < .0001 | |||
| Patel et al, 2012/India | Children and adults/prospective | SCA: Asian haplotype; VOC >3 or txn >2 in previous y | 118 (HU: 118) | 2 y | 87.2% with ↓ 50% or more | 19/20 pts txn free | High baseline HbF level | |||
| Rigano et al, 2013/Italy | Adults/retrospective | HbSβ0thal:34; HbSβ+thal:67; 2-3 VOC previous y; hx of ACS | 104 (HU: 104) | 11 y | ↓; P < .0001 | 6.7% overt stroke | ↓; P < .0001 | 30% with new/progressed SCI | ||
| Sharef et al, 2013/Oman | Children/retrospective, prospective | SCD (not specified); >3 VOC hospitalizations/y or 1 episode of ACS | 142 (HU: 142) | 4 y (1.5-10) | ↓ | ↓; P < .001 | ||||
| Singh et al, 2010/India | Adults/prospective | SCA; ≥3VOC hospitalizations/y, ACS, stroke or Hb <7 g/dL | 24 (HU: 24) | 1 y | ↓; P = .008 | ↓; P = .03 | High baseline HbF level | |||
| Steinberg et al, 2010 (MSH)/North America | Adults/prospective | SCA; MSH RCT cohort; analysis by HU use, not original trial assignment | 129/299 of original cohort deceased | Up to 17 y, 7 mo | NS | HU for at least 5 y compared with <5 y had ↓ mortality | ||||
| Voskaridou et al, 2010 (LaSHS)/Greece | Adults/prospective | HbSS: 34, HbSβ0thal: 131, HbSβ+thal: 165; ≥3 VOC/previous y; jaundice; or complications (CVA or ACS in past 5 y) | 330 (HU:131 [SCA:87; SB+thal:44]) | HU: 8 y (0.1-17); no HU: 5 y (0.1-18) | ↓; P < .001 | ↓; P = .016 | ↓; P < .001 | HU: 5; no HU: 10 | ↓; P < .001 | 10 y survival: 86% for HU; 65% for non-HU; P = .001 |
| Authors/location . | Patient population/study design . | Genotype/inclusion criteria . | N . | Follow-up period mean/median (range) . | Clinical outcomes HU vs no HU† . | Comments . | ||||
|---|---|---|---|---|---|---|---|---|---|---|
| VOC . | ACS . | Transfusion . | Stroke . | Hospital use . | ||||||
| Ali et al, 2011/Jamaica | Children/retrospective | 42 SCA, 1 HbSC; neuroimaging documentation of stroke or dx of clinical stroke | 43 (HU: 10) | HU: 4.6 y; no HU:4.2 y | HU: (2/ 100 p-y); no HU or txn: (29/100 p-y) (HR 9.4, P = .03) | Chronic transfusion program was not available | ||||
| Gilmore et al, 2011/United Kingdom | Children and adults/retrospective | 61 SCA, 1 HbSD; majority-recurrent VOC; VOC with ACS | 62 (HU: 62) | 3 y (1-9) | ↓; P = .02 at 2 y | ↓; P = .0007 at 7 y | ↓; P = .002 at 7 y | Inpatient annual days; ↓; P < .001 at 7 y | Registry data | |
| Italia et al, 2008/India | Children and adults/prospective | 54 HbSS, 23 HbSβthal; Arab-Indian haplotype; 5+ VOC/y, 1 CVA in life, 2+ ACS/life, or (AVN of femur + any of the above | 77 (HU: 77) | 2 y | ↓ | ↓ | ↓ | ↓ | ↓ | High baseline HbF level; reduction in clinical events score stratified according to initial severity (P < .0001) |
| Lobo et al, 2013/Brazil | Children/retrospective | SCD; indications for HU: recurrent VOC; >1 ACS; Hb <6 g/dL, CVA | 1760 (HU: 267 [SCA: 243; HbSB+thal: 10; HbSC: 10; HbSD: 4]) | 7 y (3-17) HU: 2 y (0.1-6.5) | HU:1 no HU: 17 | HU: 0; no HU: 4 | ↓50% P < .001 | ↓ mortality; 1 in HU group; 37 in no-HU group | ||
| ED visits ↓35% P < .001 | ||||||||||
| Nzouakou et al, 2010/France | Adults and adolescents/retrospective | SCA; ≥3 VOC hospitalizations/y; recurrent ACS; recurrent priapism; switch from txn program | 123 (HU: 123) | 4.9 y (0.44-13.5) | ↓; P < .0001 | 15/31 pts stopped txn | ↓ (data on 64 pts); P < .0001 | |||
| Patel et al, 2012/India | Children and adults/prospective | SCA: Asian haplotype; VOC >3 or txn >2 in previous y | 118 (HU: 118) | 2 y | 87.2% with ↓ 50% or more | 19/20 pts txn free | High baseline HbF level | |||
| Rigano et al, 2013/Italy | Adults/retrospective | HbSβ0thal:34; HbSβ+thal:67; 2-3 VOC previous y; hx of ACS | 104 (HU: 104) | 11 y | ↓; P < .0001 | 6.7% overt stroke | ↓; P < .0001 | 30% with new/progressed SCI | ||
| Sharef et al, 2013/Oman | Children/retrospective, prospective | SCD (not specified); >3 VOC hospitalizations/y or 1 episode of ACS | 142 (HU: 142) | 4 y (1.5-10) | ↓ | ↓; P < .001 | ||||
| Singh et al, 2010/India | Adults/prospective | SCA; ≥3VOC hospitalizations/y, ACS, stroke or Hb <7 g/dL | 24 (HU: 24) | 1 y | ↓; P = .008 | ↓; P = .03 | High baseline HbF level | |||
| Steinberg et al, 2010 (MSH)/North America | Adults/prospective | SCA; MSH RCT cohort; analysis by HU use, not original trial assignment | 129/299 of original cohort deceased | Up to 17 y, 7 mo | NS | HU for at least 5 y compared with <5 y had ↓ mortality | ||||
| Voskaridou et al, 2010 (LaSHS)/Greece | Adults/prospective | HbSS: 34, HbSβ0thal: 131, HbSβ+thal: 165; ≥3 VOC/previous y; jaundice; or complications (CVA or ACS in past 5 y) | 330 (HU:131 [SCA:87; SB+thal:44]) | HU: 8 y (0.1-17); no HU: 5 y (0.1-18) | ↓; P < .001 | ↓; P = .016 | ↓; P < .001 | HU: 5; no HU: 10 | ↓; P < .001 | 10 y survival: 86% for HU; 65% for non-HU; P = .001 |
↓, decreased; AVN, avascular necrosis; CVA, stroke; dx, diagnosis; HbSβ0thal, HbSβ0-thalassemia; HbSβ+thal, HbSβ+-thalassemia; HU, hydroxyurea; hx, history; LaSHS, Laikon Study of Hydroxyurea in Sickle Cell Syndromes; NS, not significant; p-y, patient-years; pts, patients; SCI, silent cerebral infarction; txn, transfusion.
Outcomes evaluated in single studies included cognitive function,62 physical fitness,37 perioperative,27 quality of life,63 retionopathy,23 and tricuspid regurgitant velocity.42
Pre/post comparisons in single group studies.