Drotrecogin alfa (activated): the treatment for severe sepsis?

Severe sepsis is common and increasing in incidence. Mortality rates remain high. Discovery of the link between the coagulation system and the inflammatory response to sepsis led to the development of drotrecogin alpha (activated). This recombinant form of the natural anticoagulant, activated protein C, was shown to reduce 28-day mortality from severe sepsis in a large, randomised, placebo-controlled, multi-centre Phase III study. Although subsequent studies have demonstrated that drotrecogin alpha (activated) is not of benefit to all patients with severe sepsis, it does reduce mortality rates in patients at a high risk of death. Drotrecogin alpha (activated) is associated with an increased risk of bleeding. Recent studies have shed light on its mode of action, which is primarily attributed today to cytoprotective effects especially on the endothelium with improved microcirculation. Ongoing studies will help define which patients are most likely to benefit, perhaps with the help of biochemical markers.