The risks and benefits of long-term use of hydroxyurea in sickle cell anemia: A 17.5 year follow-up.
A randomized, controlled clinical trial established the efficacy and safety of short-term use of hydroxyurea in adult sickle cell anemia. To examine the risks and benefits of long-term hydroxyurea usage, patients in this trial were followed for 17.5 years during which they could start or stop hydroxyurea. The purpose of this follow-up was to search for adverse outcomes and estimate mortality. For each outcome and for mortality, exact 95% confidence intervals were calculated, or tests were conducted at alpha = 0.05 level (P-value <0.05 for statistical significance). Although the death rate in the overall study cohort was high (43.1%; 4.4 per 100 person-years), mortality was reduced in individuals with long-term exposure to hydroxyurea. Survival curves demonstrated a significant reduction in deaths with long-term exposure. Twenty-four percent of deaths were due to pulmonary complications; 87.1% occurred in patients who never took hydroxyurea or took it for <5 years. Stroke, organ dysfunction, infection, and malignancy were similar in all groups. Our results, while no longer the product of a randomized study because of the ethical concerns of withholding an efficacious treatment, suggest that long-term use of hydroxyurea is safe and might decrease mortality.
Steinberg
Martin H
MH
Department of Medicine, Boston University School of Medicine, Boston Medical Center, Massachusetts, USA. mhsteinb@bu.edu <mhsteinb@bu.edu>
McCarthy
William F
WF
Castro
Oswaldo
O
Ballas
Samir K
SK
Armstrong
F Danny
FD
Smith
Wally
W
Ataga
Kenneth
K
Swerdlow
Paul
P
Kutlar
Abdullah
A
DeCastro
Laura
L
Waclawiw
Myron A
MA
D000293:Adolescent; D000328:Adult; D000755:Anemia, Sickle Cell / Q000150:complications / Q000188:drug therapy* / Q000401:mortality; D004249:DNA Damage; D004363:Drug Utilization; D057239:Early Termination of Clinical Trials; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D006918:Hydroxyurea / Q000009:adverse effects / Q000627:therapeutic use*; D007674:Kidney Diseases / Q000401:mortality; D008107:Liver Diseases / Q000401:mortality; D008171:Lung Diseases / Q000401:mortality; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000401:mortality; D010818:Practice Patterns, Physicians'; D011446:Prospective Studies; D018570:Risk Assessment; D018805:Sepsis / Q000401:mortality; D018709:Statistics, Nonparametric; D020521:Stroke / Q000401:mortality; D016019:Survival Analysis; D055815:Young Adult
D006918:Hydroxyurea