title: Drotrecogin alfa activated in clinical practice and the current evidences.
abstract: OBJECTIVE
  The debate on efficacy and patient safety related to the use of drotrecogin alfa (DrotAA) is timely, principally due to the negative results observed in clinical studies performed after the PROWESS study, and the economic cost-related impact of the drug on the healthcare system. The aim of this study was to review the main studies on the use of DrotAA in patients with severe sepsis. The focus was on drug efficacy-and patient safety-related issues.
  
  
  BACKGROUND
  Articles were selected by a MedLine search for studies on the use of DrotAA in patients with sepsis using the following key words: activated protein C; drotrecogin alfa; sepsis; septic shock; Xigris®. Additional references were retrieved from the studies initially selected.
  
  
  CONCLUSIONS
  Mortality and bleeding complications associated with the use of DrotAA were more frequent in large observational studies than those reported in randomized trials. In the light of the current knowledge, routine use of DrotAA should be reevaluated until well-designed confirmatory clinical trials can clarify the true efficacy and safety of the drug and help identify the subgroup of patients that can benefit from use of DrotAA. Physicians should be cautious with the rapid transfer of evidences not well-documented, to the guidelines and recommendations practiced in the care and treatment of patients with severe sepsis.
authors.affiliation: Centro de Tratamento Intensivo, Instituto Nacional de Câncer, Rio de Janeiro, RJ.
authors.forename: Márcio
authors.initials: M
authors.lastname: Soares
authors.affiliation: Serviço de Terapia Intensiva, Hospital Universitário, Universidade Federal de Santa Catarina.
authors.forename: Fernando Osni
authors.initials: FO
authors.lastname: Machado
authors.affiliation: Intensiva do Instituto Nacional de Câncer, Rio de Janeiro, RJ.
authors.forename: Viviane Bogado Leite
authors.initials: VB
authors.lastname: Torres
authors.affiliation: Comitê Coordenador, Brazilian Research in Intensive Care Network.
authors.forename: Jorge Ibrain Figueira
authors.initials: JI
authors.lastname: Salluh
authors.affiliation: AMIB.
authors.forename: André Carlos Kajdacsy-Balla
authors.initials: AC
authors.lastname: Amaral