Simvastatin in Critically Ill Patients with Covid-19

被引：29

作者：

Hills, Thomas E. ^{[1
,2
,3
,5
]}

Lorenzi, Elizabeth ^{[1
,2
,3
,5
]}

Berry, Lindsay R. ^{[1
,3
,5
]}

Shyamsundar, Murali ^{[6
,7
]}

Al-Beidh, Farah ^{[10
]}

Annane, Djillali ^{[19
,20
,21
,22
]}

Arabi, Yaseen ^{[23
,24
]}

Aryal, Diptesh ^{[25
,26
]}

Au, Carly ^{[11
]}

Beane, Abigail ^{[14
,26
]}

Bhimani, Zahra ^{[27
]}

Bonten, Marc ^{[38
,40
]}

Bradbury, Charlotte A. ^{[16
,17
]}

Brunkhorst, Frank M. ^{[42
]}

Burrell, Aidan ^{[45
,47
]}

Buxton, Meredith ^{[52
]}

Calfee, Carolyn S. ^{[53
,54
]}

Cecconi, Maurizio ^{[56
,57
]}

Cheng, Allen C. ^{[45
,46
,48
]}

Cove, Matthew E. ^{[58
]}

Detry, Michelle A. ^{[1
,5
]}

Estcourt, Lise J. ^{[18
]}

Fitzgerald, Mark ^{[1
,5
,45
]}

Goligher, Ewan C. ^{[28
,29
]}

Goossens, Herman ^{[61
]}

Green, Cameron ^{[45
]}

Haniffa, Rashan ^{[12
,15
,62
]}

Harrison, David A. ^{[11
]}

Hashmi, Madiha ^{[63
]}

Higgins, Alisa M. ^{[45
]}

Huang, David T. ^{[64
,65
]}

Ichihara, Nao ^{[66
,67
]}

Jayakumar, Deva ^{[59
]}

Kruger, Peter S. ^{[49
,50
]}

Lamontagne, Francois ^{[32
]}

Lampro, Lamprini ^{[11
]}

Lawler, Patrick R. ^{[30
,33
]}

Marshall, John C. ^{[27
,31
]}

Mason, Alexina J. ^{[11
]}

McGlothlin, Anna ^{[3
,4
,5
]}

McGuinness, Shay ^{[1
,3
,5
]}

McQuilten, Zoe K. ^{[45
,48
]}

McVerry, Bryan J. ^{[64
,65
]}

Mouncey, Paul R. ^{[11
]}

Murthy, Srinivas ^{[34
]}

Neal, Matthew D. ^{[64
]}

Nichol, Alistair D. ^{[45
,47
,69
]}

O'Kane, Cecilia M. ^{[6
]}

Parke, Rachael L. ^{[3
,4
,5
]}

Parker, Jane C. ^{[45
]}

机构：

[1] Med Res Inst New Zealand, Wellington, New Zealand

[2] Middlemore Hosp, Auckland, New Zealand

[3] Te Toka Tumai Auckland City Hosp, Auckland, New Zealand

[4] Univ Auckland, Sch Nursing, Auckland, New Zealand

[5] Berry Consultants, Austin, TX USA

[6] Queens Univ Belfast, Wellcome Wolfson Inst Expt Med, 97 Lisburn Rd,Rm 02-057, Belfast BT9 7AE, Antrim, North Ireland

[7] Belfast Hlth & Social Care Trust, Dept Crit Care, Belfast, Antrim, North Ireland

[8] Queens Univ Belfast, Belfast Hlth & Social Care Trust, Ctr Publ Hlth, Belfast, Antrim, North Ireland

[9] Dept Hlth, Belfast, Antrim, North Ireland

[10] Imperial Coll London, London, England

[11] Intens Care Natl Audit & Res Ctr, London, England

[12] Univ Coll London Hosp, London, England

[13] Imperial Coll Healthcare NHS Trust, London, England

[14] Univ Edinburgh, Inst Regenerat & Repair, Edinburgh, Midlothian, Scotland

[15] Univ Edinburgh, Ctr Inflammat Res, Edinburgh, Midlothian, Scotland

[16] Univ Bristol, Fac Hlth Sci, Bristol, Avon, England

[17] Univ Hosp Bristol & Weston NHS Trust, Bristol Haematol & Oncol Ctr, Bristol, Avon, England

[18] NHS Blood & Transplant, Oxford, England

[19] Univ Paris Saclay, Inst Hosp Univ Prometheus, Garches, France

[20] Univ Versailles St Quentin Univ Paris Saclay, Raymond Poincare Hosp, Assistance Publ Hop Paris, Dept Intens Care, Garches, France

[21] Univ Versailles St Quentin Univ Paris Saclay, Lab Infect & Inflammat Unite 173, Sch Med Simone Veil, INSERM, Garches, France

[22] Federat Hosp Univ Sepsis Saclay & Paris Seine Nor, Garches, France

[23] King Saud Bin Abdulaziz Univ Hlth Sci, Riyadh, Saudi Arabia

[24] King Abdullah Int Med Res Ctr, Riyadh, Saudi Arabia

[25] Nepal Intens Care Res Fdn, Kathmandu, Nepal

[26] Mahidol Oxford Trop Med Res Unit MORU, Bangkok, Thailand

[27] Unity Hlth Toronto, Toronto, ON, Canada

[28] Univ Toronto, Interdept Div Crit Care Med, Toronto, ON, Canada

[29] Toronto Gen Hosp, Res Inst, Toronto, ON, Canada

[30] Univ Hlth Network, Peter Munk Cardiac Ctr, Toronto, ON, Canada

[31] Keenan Ctr Biomed Res, Toronto, ON, Canada

[32] Univ Sherbrooke, Sherbrooke, PQ, Canada

[33] McGill Univ, Hlth Ctr, Montreal, PQ, Canada

[34] Univ British Columbia, Fac Med, Vancouver, BC, Canada

[35] Univ Laval, Res Ctr, Ctr Hosp Univ Quebec, Populat Hlth & Optimal Practices Res Unit, Quebec City, PQ, Canada

[36] Univ Manitoba, Winnipeg, MB, Canada

[37] CancerCare Manitoba, Winnipeg, MB, Canada

[38] Univ Utrecht, Univ Med Ctr Utrecht, Julius Ctr Hlth Sci & Primary Care, Utrecht, Netherlands

[39] Univ Utrecht, Univ Med Ctr Utrecht, Intens Care Ctr, Utrecht, Netherlands

[40] European Clin Res Alliance Infect Dis, Utrecht, Netherlands

[41] Radboud Univ Nijmegen, Med Ctr, Nijmegen, Netherlands

[42] Friedrich Schiller Univ, Jena Univ Hosp, Dept Anesthesiol & Intens Care Med, Jena, Germany

[43] Friedrich Schiller Univ, Jena Univ Hosp, Inst Infect Dis & Infect Control, Jena, Germany

[44] Hans Knoell Inst, Leibniz Inst Nat Prod Res & Infect Biol, Jena, Germany

[45] Monash Univ, Sch Publ Hlth & Prevent Med, Melbourne, Vic, Australia

[46] Monash Univ, Sch Clin Sci, Melbourne, Vic, Australia

[47] Alfred Hosp, Melbourne, Vic, Australia

[48] Monash Hlth, Melbourne, Vic, Australia

[49] Univ Queensland, Fac Med, Brisbane, Qld, Australia

[50] Princess Alexandra Hosp, Intens Care Unit, Brisbane, Qld, Australia

来源：

NEW ENGLAND JOURNAL OF MEDICINE | 2023年 / 389卷 / 25期

关键词：

LATENT CLASS ANALYSIS; INFLAMMATION; METAANALYSIS; MORTALITY;

D O I：

10.1056/NEJMoa2309995

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

BackgroundThe efficacy of simvastatin in critically ill patients with coronavirus disease 2019 (Covid-19) is unclear.MethodsIn an ongoing international, multifactorial, adaptive platform, randomized, controlled trial, we evaluated simvastatin (80 mg daily) as compared with no statin (control) in critically ill patients with Covid-19 who were not receiving statins at baseline. The primary outcome was respiratory and cardiovascular organ support-free days, assessed on an ordinal scale combining in-hospital death (assigned a value of -1) and days free of organ support through day 21 in survivors; the analyis used a Bayesian hierarchical ordinal model. The adaptive design included prespecified statistical stopping criteria for superiority (>99% posterior probability that the odds ratio was >1) and futility (>95% posterior probability that the odds ratio was <1.2).ResultsEnrollment began on October 28, 2020. On January 8, 2023, enrollment was closed on the basis of a low anticipated likelihood that prespecified stopping criteria would be met as Covid-19 cases decreased. The final analysis included 2684 critically ill patients. The median number of organ support-free days was 11 (interquartile range, -1 to 17) in the simvastatin group and 7 (interquartile range, -1 to 16) in the control group; the posterior median adjusted odds ratio was 1.15 (95% credible interval, 0.98 to 1.34) for simvastatin as compared with control, yielding a 95.9% posterior probability of superiority. At 90 days, the hazard ratio for survival was 1.12 (95% credible interval, 0.95 to 1.32), yielding a 91.9% posterior probability of superiority of simvastatin. The results of secondary analyses were consistent with those of the primary analysis. Serious adverse events, such as elevated levels of liver enzymes and creatine kinase, were reported more frequently with simvastatin than with control.ConclusionsAlthough recruitment was stopped because cases had decreased, among critically ill patients with Covid-19, simvastatin did not meet the prespecified criteria for superiority to control.

引用

页码：2341 / 2354

页数：14

共 33 条

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