A multicenter randomized trial of atorvastatin therapy in intensive care patients with severe sepsis

Abstract

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, doubleblind, 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 (20mgdaily) or matched placebo. MEASUREMENTS AND MAIN RESULTS: There was no difference in IL-6 concentrations (primary end point) between the atorvastatin and placebo groups (P¼0.76) and no interaction between treatment group and time to suggest that the groups behaved differently over time (P ¼ 0.26). Baseline plasma IL-6 was lower among previous statin users (129 [87–191] vs. 244 [187–317] pg/ml; P ¼ 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 betweenthetwogroups. Cholesterolwaslower in patients treatedwith atorvastatin (2.4 [0.07] vs. 2.6 [0.06] mmol/L; P ¼ 0.006). In the predefined group of 77 prior statin users, those randomized to placebo hada greater 28-day mortality(28%vs.5%;P¼0.01) compared with those who received atorvastatin. The difference was not statistically significant at 90 days (28% vs. 11%; P ¼ 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).