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

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

Am J Respir Crit Care Med. 2019 Jun 17;:

Authors: Sapey E, Patel JM, Greenwood H, Walton GM, Grudzinska F, Parekh D, Mahida RY, Dancer RC, Lugg ST, Howells PA, Hazeldine J, Newby P, Scott A, Nightingale P, Hill AT, Thickett DR

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, ID: 2012-003343-29.

PMID: 31206313 [PubMed - as supplied by publisher]

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