Recent publications have focused on the patterns of survival in patients with severe sepsis (Macias and Nelson, Crit Care Med 2004:32:S232-238). Drotrecogin alfa (activated)[DrotAA] has been shown to improve survival in severe sepsis in a large phase III clinical trial, PROWESS. We hypothesized that the pattern of survival benefit in PROWESS is different depending on the baseline disease severity.
Of the 1690 PROWESS patients, 1057 (63%) were on a vasopressor at baseline. Kaplan-Meier and hazard estimates were used to examine survival patterns, and Chi-square tests were used to compare causes of death between patients on vasopressors at baseline with those that were not.
As the below illustrates, there was a similar 28-day survival benefit with DrotAA in patients with and without vasopressor requirement at baseline. The pattern of survival over the 28-day period was quite different in these two groups. In the vasopressor group, there was an early separation in the survival curves over the first 2 weeks which persisted to 28 days. However, in the no vasopressor group there was no separation in the curves until Day 14. Within the placebo and DrotAA groups, the vasopressor versus the no vasopressor group had more deaths from septic shock and less deaths from non-cardiac organ failure, p = 0.02 and p = 0.04, respectively. DrotAA treated patients had less septic shock deaths than placebo-treated patients in PROWESS, p = 0.08.
Survival pattern from Drot AA in PROWESS differs based on baseline disease severity as assessed by vasopressor status. This difference in survival correlated with differences in cause of death.
These differences in survival pattern in DAA-treated patients may be explained by different primary mechanism of action of DAA. Further investigation into the mechanism of action of DAA with clinical correlation will be important to optimize this new therapy. figure
M.D. Williams, Eli Lilly and Co.