A Multicenter Randomized Trial of Atorvastatin Therapy in Intensive Care Patients with Severe Sepsis
A Multicenter Randomized Trial of Atorvastatin Therapy in Intensive Care Patients with Severe Sepsis
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DOI：
10.1164/rccm.201209-1718oc
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发表时间：
2013-04-01
影响因子：
24.7
通讯作者：
Venkatesh, Bala
中科院分区：
文献类型：
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作者：
Kruger, Peter;Bailey, Michael;Venkatesh, Bala
基本原理：Observational studies link statin therapy with improved outcomes in patients with severe sepsis.Objectives：To test whether avastatin therapy affects biological and clinical outcomes in critical illness patients with severe sepsis.Methods：Phase II，multicenter，prospective，randomized，double-blind，placebo-controlled trial layered by site and prior statin use. 250名重症患者的队列研究（123例他汀类药物，127例安慰剂）严重脓毒症患者接受阿托伐他汀或（每日20毫克）或匹配的安慰剂。IL-6浓度无差异（主要终点）（P = 0.76），治疗组与时间之间无相互作用，表明各组随时间推移表现不同（P = 0.26）。既往他汀类药物使用者的基线血浆IL-6较低（129 [87-191] vs. 244 [187-317] pg/ml; P = 0.01）。两组之间的住院时间、序贯器官衰竭评估评分变化或重症监护室出院时、出院时、28天或90天死亡率（15% vs. 19%）或不良反应无差异。接受阿托伐他汀治疗的患者胆固醇较低（2.4 [0.07] vs. 2.6 [0.06] mmol/L; P = 0.006）。在预先定义的77名既往他汀类药物使用者中，随机分配至安慰剂组的患者与接受阿托伐他汀组的患者相比，28天死亡率更高（28% vs. 5%; P = 0.01）。90天时的差异无统计学意义（28% vs. 11%; P = 0.06）。结论：阿托伐他汀治疗严重脓毒症不影响IL-6水平。既往使用他汀类药物与较低的基线IL-6浓度相关，在该队列中继续使用阿托伐他汀与生存率改善相关。
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 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).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).