Drotrecogin alfa (activated) treatment of older patients with severe sepsis.
The incidence of severe sepsis increases dramatically with advanced age, with a mortality rate that approaches 50%. The main purpose of this investigation was to determine both short- and long-term survival outcomes among 386 patients aged >or=75 years who were enrolled in the Protein C Worldwide Evaluation of Severe Sepsis (PROWESS) trial. Subjects who were treated with drotrecogin alfa (activated; DAA) had absolute risk reductions in 28-day and in-hospital mortality of 15.5% and 15.6%, respectively (P=.002 for both), compared with placebo recipients. The relative risk (RR) for 28-day mortality was 0.68 (95% confidence interval [CI], 0.54-0.87), and the in-hospital RR was 0.70 (95% CI, 0.56-0.88). Resource use and patient disposition for DAA-treated patients compared favorably with those for placebo recipients. In addition, long-term follow-up data were available for 375 subjects (97.2%), and survival rates for DAA recipients were significantly higher over a 2-year period (P=.02). The incidences of serious adverse bleeding during the 28-day study period in the DAA and placebo groups were 3.9% and 2.2%, respectively (P=.34). There was no interaction between age and bleeding rates (P=.97). In conclusion, older patients with severe sepsis have higher short- and long-term survival rates when treated with DAA than when treated with placebo but an increased risk of serious bleeding that is not aged related.
Ely
E Wesley
EW
Division of Allergy, Center for Health Services Research, Vanderbilt University School of Medicine, Nashville, Tennessee 37232-8300 , USA. wes.ely@vanderbilt.edu
Angus
Derek C
DC
Williams
Mark D
MD
Bates
Becky
B
Qualy
Rebecca
R
Bernard
Gordon R
GR
D000368:Aged; D000369:Aged, 80 and over; D000890:Anti-Infective Agents / Q000009:adverse effects / Q000627:therapeutic use*; D004311:Double-Blind Method; D005260:Female; D006295:Health Resources; D006801:Humans; D008297:Male; D009017:Morbidity; D015999:Multivariate Analysis; D011446:Prospective Studies; D011486:Protein C / Q000009:adverse effects / Q000627:therapeutic use*; D011994:Recombinant Proteins / Q000009:adverse effects / Q000627:therapeutic use*; D018805:Sepsis / Q000188:drug therapy* / Q000401:mortality; D015996:Survival Rate; D016896:Treatment Outcome
D000890:Anti-Infective Agents; D011486:Protein C; D011994:Recombinant Proteins; C421124:drotrecogin alfa activated