Sickle cell anaemia: hydroxyurea reduced episodes of acute chest syndrome and transfusions.

Clinical bottom line (level 1b)

  1. Patients with sickle cell anaemia and frequent crises who were given hydroxyurea, were less likely to have acute chest syndrome (NNT = 5 at 21 months) , or blood transfusions (NNT = 6 at 21 months) than those given placebo.
  2. Patients given hydroxyurea were less likely to have crises.
  3. There was no clear difference in patients having medication stopped permanently between the two groups.
Charache et al: New England Journal of Medicine 1995; 332 (20): 1317-1322
Expires March 2003

The study

Double-blinded concealed randomised trial without intention-to-treat
Setting: 21 centres, USA and Canada

299 patients (aged ?, ?% male) with sickle cell anaemia and at least three painful crises in the last year

Excluded if
  • <18 years old
  • beta-thalassaemia
  • pregnant
  • narcotic addiction or >30 oxydone tablets every two weeks
  • in a long term transfusion program
  • concurrent treatment with another antisickling drug
  • blood counts unable to be distinguished from marrow depression
  • history of stroke in last six years
  • prior hydroxyurea treatment
  • HIV positive

Control Group: (n = 147, 147 analysed): placebo
Experimental Group: (n = 152, 152 analysed): hydroxyurea , initial dose 15 mg/kg/day, increased by 5 mg/kg/day every 12 weeks to maximum of 35 mg/kg/day, unless marrow depression noted. If this occurred, therapy was stopped until recovery.
All patients received 1 mg folate daily
93% followed for 21 months

The evidence

Outcome Time to outcome CEREERRRR
(95% CI)		ARR
(95% CI)		NNT
(95% CI)
acute chest syndrome 21 months 51
(34.7%)		 25
(16.5%)		 53.0%
(28.0% to 69.0%)		 18.3%
(8.55% to 27.9%)		 5
(4 to 12)
blood transfusions 21 months 73
(49.7%)		 48
(31.6%)		 36.0%
(15.0% to 52.0%)		 18.1%
(7.13% to 29.0%)		 6
(3 to 14)
death 21 months 5
(3.40%)		 2
(1.32%)		 61.0%
(-96.0% to 92.0%)		 2.09%
(-1.36% to 5.53%)		 48
(NNT = 18 to infinity;
NNH = 74 to infinity)
medication stopped permanently 21 months 6
(4.08%)		 14
(9.21%)		 -126%
(-471% to 11.0%)		 -5.13%
(-10.7% to 0.47%)		 -19
(NNT = 212 to infinity;
NNH = 9 to infinity)

Outcome Control Group
(SD)		 Experimental Group
(SD)		 Mean Difference
(95% CI)
median crises per year 4.50
() 		2.50
() 		2.00
( to )

  • The P-value for the difference between the number of crises per year was <0.001.

Comments

  1. 66% of patients had previous chest syndrome; 31% ankle ulcers; 20% aseptic necrosis of bone; 2% aplastic anaemia due to parvovirus.
  2. One death in the placebo group was due to homicide.
  3. 75% of patients took more than 80% of the medication.
  4. Almost all patients had to temporarily stop medication due to bone marrow suppression.
  5. About a third of patients had ten or more crises per year before study entry.

Citation

  1. Charache S, Terrin ML, Moore RD, et al: Effect of hydroxyurea on the frequency of painful crises in sickle cell anemia. New England Journal of Medicine 1995; 332 (20): 1317-1322
Contributor: Chris Ball and Clare Wotton, March 2000
Reviewer:

Clinical Question.
Patient sickle cell anaemia
Intervention or Exposure hydroxyurea
Comparison placebo
Outcome death, acute chest syndrome and blood transfusions