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First, in stopping early after a predefined interim analysis, the PROWESS trial probably overestimated the treatment effect [ 16, 17].
Subgroup analysis of PROWESS and the subsequent ADDRESS [ 2] study have shown that only the sickest patients (at least two organ failures or APACHE II score >25) benefit from APC. Treatment is associated with an increased risk of serious bleeding, and so the use of APC is contraindicated in patients at high risk for this complication.
In the present analysis of PROWESS-Shock trial, we confirmed that steroid use in usual care was indeed reserved for more critically ill individuals.
An analysis of the PROWESS data indicates that 36.2% of the 1690 PROWESS patients met the AEC without the 8-hour time restriction and 5.7% met the criteria with the 8-hour time restriction for enrollment in the study by Annane and coworkers [ 15].
Dhainaut et al. [ 25] showed in subgroup analysis of the PROWESS trial that IL-6 levels fell more rapidly in the rhAPC group than in the control group.
The European regulatory body approved rhAPC for multiple organ failure (again based on subset data analysis from the PROWESS trial demonstrating increased treatment effect as the number of organ failures increased).
In a subgroup analysis of the PROWESS trial, patients with higher risk of death had a larger drop in hospital mortality compared to patients with a lower risk of death.
In the present retrospective analysis of the PROWESS-Shock trial database, we were unable to find a noticeable positive impact from intravenous steroids for treatment of septic shock at baseline either in patients randomized to DrotAA or those randomized to placebo.
Expert analysis: Nicola Sturgeon's debating prowess left others for dust.
Finally, analysis from the original PROWESS data showed absolutely no difference in aPC benefit regardless of whether patients were treated with steroids [ 10].
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Justyna Jupowicz-Kozak
CEO of Professional Science Editing for Scientists @ prosciediting.com