A Multicenter Randomized Trial of Atorvastatin Therapy in Intensive Care Patients with Severe Sepsis

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Rationale:Observational studies link statin therapy with improved outcomes in patients with severe sepsis.Objectives:To test whether atorvastatin therapy affects biologic and clinical outcomes in critically ill patients with severe sepsis.Methods:Phase II, multicenter, prospective, randomized, double-blind, placebo-controlled trial stratified by site and prior statin use. A cohort of 250 critically ill patients (123 statins, 127 placebo) with severe sepsis were administrated either atorvastatin (20 mg daily) or matched placebo.Measurements and Main Results:There was no difference in IL-6 concentrations (primary end point) between the atorvastatin and placebo groups (P= 0.76) and no interaction between treatment group and time to suggest that the groups behaved differently over time (P= 0.26). Baseline plasma IL-6 was lower among previous statin users (129 [87-191] vs. 244 [187-317] pg/ml;P= 0.01). There was no difference in length of stay, change in Sequential Organ Failure Assessment scores or mortality at intensive care unit discharge, hospital discharge, 28- or 90-day (15% vs. 19%), or adverse effects between the two groups. Cholesterol was lower in patients treated with atorvastatin (2.4 [0.07] vs. 2.6 [0.06] mmol/L;P= 0.006). In the predefined group of 77 prior statin users, those randomized to placebo had a greater 28-day mortality (28% vs. 5%;P= 0.01) compared with those who received atorvastatin. The difference was not statistically significant at 90 days (28% vs. 11%;P= 0.06).Conclusions:Atorvastatin therapy in severe sepsis did not affect IL-6 levels. Prior statin use was associated with a lower baseline IL-6 concentration and continuation of atorvastatin in this cohort was associated with improved survival.Clinical trial registered with the Australian New Zealand Clinical Trials Registry (ACTRN 12607000028404).

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