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

作者：Kruger Peter^*; Bailey Michael; Bellomo Rinaldo; Cooper David James; Harward Meg; Higgins Alisa; Howe Belinda; Jones Darryl; Joyce Chris; Kostner Karam; McNeil John; Nichol Alistair; Roberts Michael S; Syres Gillian; Venkatesh Bala

来源：American Journal of Respiratory and Critical Care Medicine, 2013, 187(7): 743-750.

DOI：10.1164/rccm.201209-1718OC

• statin
• 3-hydroxy-3-methylglutaryl CoA reductase inhibitor
• sepsis
• critical illness
• mortality

Rationale: Observational studies link statin therapy with improved outcomes in patients with severe sepsis. %26lt;br%26gt;Objectives: To test whether atorvastatin therapy affects biologic and clinical outcomes in critically ill patients with severe sepsis. %26lt;br%26gt;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. %26lt;br%26gt;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 pre-defined 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). %26lt;br%26gt;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. %26lt;br%26gt;Clinical trial registered with the Australian New Zealand Clinical Trials Registry (ACTRN 12607000028404).

• 出版日期2013-4-1