#Simvastatin Improves #Neutrophil Function and Clinical #Outcomes in #Pneumonia: a Pilot #RCT (Am J Respir Crit Care Med., abstract)

[Source: US National Library of Medicine, full page: (LINK). Abstract, edited.]

Am J Respir Crit Care Med. 2019 Jun 17. doi: 10.1164/rccm.201812-2328OC. [Epub ahead of print]

Simvastatin Improves Neutrophil Function and Clinical Outcomes in Pneumonia: a Pilot Randomised Controlled Trial.

Sapey E1, Patel JM2, Greenwood H3, Walton GM4, Grudzinska F4, Parekh D5, Mahida RY2, Dancer RC3, Lugg ST4, Howells PA6, Hazeldine J2, Newby P4, Scott A3, Nightingale P7, Hill AT8, Thickett DR9.

Author information: 1 University of Birmingham, Institute of Inflammation and Ageing, Birmingham, United Kingdom of Great Britain and Northern Ireland ; e.sapey@bham.ac.uk. 2 University of Birmingham, 1724, Institute of Inflammation and Ageing, Birmingham, West Midlands, United Kingdom of Great Britain and Northern Ireland. 3 University of Birmingham, Institute of Inflammation and Aging, Birmingham, United Kingdom of Great Britain and Northern Ireland. 4 University of Birmingham, Institute of Inflammation and Ageing, Birmingham, West Midlands, United Kingdom of Great Britain and Northern Ireland. 5 University of Birmingham, Critical Care and Pain Perioperative, Critical Care and Trauma Trials Group, School of Clinical and Experimental Medicine,, Birmingham, United Kingdom of Great Britain and Northern Ireland. 6 University of Birmingham, Centre for Translational Inflammation Research, Birmingham, United Kingdom of Great Britain and Northern Ireland. 7 University Hospital Birmingham NHS Foundation Trust, Statistics, Birmingham, United Kingdom of Great Britain and Northern Ireland. 8 Royal Infirmary of Edinburgh, Respiratory Medicine, Scotland, Edinburgh, United Kingdom of Great Britain and Northern Ireland. 9 University of Birmingham, Lung Injury and Fibrosis Treatment Programme, Birmingham, United Kingdom of Great Britain and Northern Ireland.

 

Abstract

RATIONALE:

Population studies suggest improved sepsis outcomes with statins but randomized controlled trials in patients with sepsis and organ dysfunction in critical care settings have broadly been negative. In vitro data suggest statins modulate age-related neutrophil functions improving neutrophil responses to infection, but only in older patients and at high dose.

OBJECTIVE:

To determine if high dose simvastatin improved neutrophil functions and clinical outcomes in hospitalized older adults with community acquired pneumonia with sepsis (CAP+S) not admitted to critical care.

METHODS:

A randomized, double-blinded, placebo-controlled pilot study of simvastatin 80mg or placebo for 7 days for CAP+S patients aged >55 years admitted to a secondary care hospital. Day 4 primary endpoint was change in neutrophil NETosis. Day 4 secondary endpoints included neutrophil chemotaxis, safety and tolerability, Sequential Organ Failure Assessment(SOFA) score, mortality, readmission and markers of tissue degradation/inflammation.

RESULTS:

Four days of simvastatin adjuvant therapy in CAP+S was associated with improvements in systemic neutrophil function (NETosis and chemotaxis), a reduction in systemic neutrophil elastase burden and improved SOFA scores compared with placebo. A post-hoc analysis demonstrated simvastatin therapy was associated with improved hospital-free survival compared to placebo. Simvastatin was well tolerated in this elderly and multi-morbid patient group with common co-prescription of macrolide antibiotics.

CONCLUSION:

This pilot study supports high-dose simvastatin as an adjuvant therapy in CAP+S in an older and milder disease cohort than assessed previously. A definitive multi-centred study is now warranted in this population to assess the likelihood of benefit and harm. Clinical trial registration available at clinicaltrialsregister.eu/ctr-search/search, ID: 2012-003343-29.

KEYWORDS: elderly care; innate immunity; pneumonia; sepsis; statin

PMID: 31206313 DOI: 10.1164/rccm.201812-2328OC

Keywords: Pneumonia; Sepsis; Statins.

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gimi69

I am an Italian blogger, active since 2005 with main focus on emerging infectious diseases such as avian influenza, SARS, antibiotics resistance, and many other global Health issues. Other fields of interest are: climate change, global warming, geological and biological sciences. My activity consists mainly in collection and analysis of news, public services updates, confronting sources and making decision about what are the 'signals' of an impending crisis (an outbreak, for example). When a signal is detected, I follow traces during the entire course of an event. I started in 2005 my blog ''A TIME'S MEMORY'', now with more than 40,000 posts and 3 millions of web interactions. Subsequently I added an Italian Language blog, then discontinued because of very low traffic and interest. I contributed for seven years to a public forum (FluTrackers.com) in the midst of the Ebola epidemic in West Africa in 2014, I left the site to continue alone my data tracking job.

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