Intensive Care Unit, Princess Alexandra Hospital, Wooloongabba, Brisbane, Australia.
Am J Respir Crit Care Med. 2013 Apr 1;187(7):743-50. doi: 10.1164/rccm.201209-1718OC.
Observational studies link statin therapy with improved outcomes in patients with severe sepsis.
To test whether atorvastatin therapy affects biologic and clinical outcomes in critically ill patients with severe sepsis.
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.
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).
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).
观察性研究表明他汀类药物治疗可改善严重脓毒症患者的预后。
检测阿托伐他汀治疗是否影响严重脓毒症危重症患者的生物学和临床结局。
这是一项 2 期、多中心、前瞻性、随机、双盲、安慰剂对照试验，根据地点和既往他汀类药物使用情况进行分层。250 例严重脓毒症患者（阿托伐他汀组 123 例，安慰剂组 127 例）接受阿托伐他汀（20 mg/日）或匹配安慰剂治疗。
阿托伐他汀组和安慰剂组的白细胞介素 6 浓度（主要终点）无差异（P = 0.76），且治疗组与时间之间无交互作用，提示两组随时间变化的行为不同（P = 0.26）。既往他汀类药物使用者的基线血浆白细胞介素 6 水平较低（129[87-191]比 244[187-317]pg/ml；P = 0.01）。两组患者的 ICU 出院时、出院时、28 天和 90 天的住院时间、序贯器官衰竭评估评分变化或死亡率，以及不良反应均无差异。阿托伐他汀治疗组的胆固醇水平较低（2.4[0.07]比 2.6[0.06]mmol/L；P = 0.006）。在 77 例既往他汀类药物使用者的预设组中，与接受阿托伐他汀治疗的患者相比，随机分配至安慰剂组的患者在 28 天的死亡率更高（28%比 5%；P = 0.01），但在 90 天的死亡率差异无统计学意义（28%比 11%；P = 0.06）。
严重脓毒症患者应用阿托伐他汀治疗并未影响白细胞介素 6 水平。既往他汀类药物的使用与较低的基线白细胞介素 6 浓度相关，而本队列中继续使用阿托伐他汀与生存改善相关。临床试验在澳大利亚新西兰临床试验注册中心（ACTRN 12607000028404）注册。
