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.
Recommended CitationSteinberg, M. H.; McCarthy, W. F.; Castro, O.; Ballas, S. K.; Armstrong, F. D.; Smith, W.; Ataga, K.; Swerdlow, P.; Kutlar, A.; DeCastro, L.; Waclawiw, M. A.; Orringer, E.; Jones, S.; Strayhorn, D.; Rosse, W.; Phillips, G.; Pearce, D.; Johnson-Telfair, A.; Daitch, L.; Milner, P.; Tracy, A.; Valdez, S.; Allen, G. E.; Moshang, J.; Scott, B.; Bigelow, C.; Anderson, A.; Sabahi, V.; Harrington, T.; Labrousse, W.; Pegelow, C.; Temple, D.; Case, E.; Harrell, R.; Childerie, S.; Embury, S.; Schmidt, B.; Davies, D.; Saunthararajah, Y.; Koshy, M.; Talischy-Zahed, N.; Dorn, L.; Pendarvis, G.; McGee, M.; Telfer, M.; Davis, A.; Onyekwere, O. C.; Nwokolo, C.; Finke, H.; Perlin, E.; Siteman, J.; Bryan, M.; Saunders, T.; Barber, Y.; Gascon, P.; Di Paolo, P.; Gargiulo, S.; Eckman, J.; Carter-Randall, E.; Bailey, J. H.; Platt, A.; Waller, L.; Ramirez, G.; Knors, V.; Hernandez, S.; Rodriguez, E. M.; Wilkes, E.; Vichinsky, E.; Hagar, W.; Hoehner, C.; Hackney-Stevens, E.; Claster, S.; Earles, A.; Kleman, K.; McLaughlin, K.; White, L.; Maddox, B.; Usry, L.; Brenner, A.; Williams, K.; O'Brien, R.; Genther, K.; Shurin, S.; Berman, B.; Chiarucci, K.; Keverline, L.; Olivieri, N.; Chow, J.; Hui, M.; Shaw, D.; Lewis, N.; Okam, M.; Mandell, E.; Palmer, A.; Bridges, K.; Tynan, B.; Winograd, C.; Bellevue, R.; Dosik, H.; Sheikhai, M.; Ryans, P.; Souffrant, H.; Adler, B.; Johnson-Telfair, A.; Eskridge, L.; Prchal, J.; Braddock, J.; McArdle, T.; Carlos, T.; Roundtree-Schmotzer, A.; and Gardner, D., "The risks and benefits of long-term use of hydroxyurea in sickle cell anemia: A 17.5 year follow-up." (2010). Department of Medicine Faculty Papers. Paper 45.