The effects of statin therapy on inflammatory cytokines in patients with bacterial infections: a randomized double-blind placebo controlled clinical trial.
ABSTRACT To determine if statin therapy reduces the incidence of severe sepsis and the levels of inflammatory cytokines in patients with acute bacterial infection.
Double-blind placebo controlled randomized clinical trial.
Department of medicine and medical intensive care unit in a tertiary university medical center.
A total of 83 patients with suspected or documented bacterial infection were enrolled. We randomly assigned 42 patients to receive 40 mg of simvastatin orally, followed by 20 mg of simvastatin, and 41 to receive matching placebo.
The study was prematurely terminated due to slow recruitment rate. Here we report the analysis of the secondary outcome: change in cytokines levels at 72 h. Both groups were evenly matched in terms of co-morbidity and severity of illness on admission. Four of the 83 patients enrolled developed severe sepsis, two in each group. No difference was observed in other clinical variables and there were no mortalities. Cytokine levels were randomly assessed in 40 patients (20 in each group). Both TNF-alpha and IL-6 levels were significantly reduced in the simvastatin group (p = 0.02 and p = 0.02, respectively), while no such difference was observed in the placebo group (p = 0.35 and 0.39, respectively).
Statin therapy may be associated with a reduction in the levels of inflammatory cytokines in patients with acute bacterial infections. Large controlled trials will determine if this reduction will translate into a clinical benefit.
Article: Randomized double-blind placebo-controlled trial of 40 mg/day of atorvastatin in reducing the severity of sepsis in ward patients (ASEPSIS Trial).[show abstract] [hide abstract]
ABSTRACT: INTRODUCTION: Several observational studies suggest that statins modulate the pathophysiology of sepsis and may prevent its progression. The aim of this study was to determine if the acute administration of atorvastatin reduces sepsis progression in statin naive patients hospitalized with sepsis. METHODS: A single centre phase II randomized double-blind placebo-controlled trial. Patients with sepsis were randomized to atorvastatin 40mg daily or placebo for the duration of their hospital stay up to a maximum of 28-days. The primary end-point was the rate of sepsis progressing to severe sepsis during hospitalization. RESULTS: 100 patients were randomized, 49 to the treatment with atorvastatin and 51 to placebo. Patients in the atorvastatin group had a significantly lower conversion rate to severe sepsis compared to placebo (4% vs. 24% p=0.007.), with a number needed to treat of 5. No significant difference in length of hospital stay, critical care unit admissions, 28-day and 12-month readmissions or mortality was observed. Plasma cholesterol and albumin creatinine ratios were significantly lower at day 4 in the atorvastatin group (p<0.0001 and p=0.049 respectively). No difference in adverse events between the two groups was observed (p=0.238). CONCLUSIONS: Acute administration of atorvastatin in patients with sepsis may prevent sepsis progression. Further multi-centre trials are required to verify these findings. Trial Registration: International Standard Randomised Control Trial Registry ISRCTN64637517.Critical care (London, England) 12/2012; 16(6):R231. · 4.61 Impact Factor
Article: Effect of immunomodulatory therapies in patients with pandemic influenza A (H1N1) 2009 complicated by pneumonia.[show abstract] [hide abstract]
ABSTRACT: To determine the effect of immunomodulatory therapies on the development of severe disease in hospitalized adults with laboratory-confirmed pandemic influenza A (H1N1) 2009 complicated by pneumonia. Observational, prospective cohort study at thirteen tertiary hospitals in Spain. The use of corticosteroids, macrolides and statins was recorded. The outcome of interest was severe disease, defined as the composite of intensive care unit admission or death after the first day of hospitalization. Of the 197 patients with pandemic influenza A (H1N1) 2009 complicated by pneumonia, 68 (34.5%) received some anti-inflammatory therapy since hospital admission (corticosteroids in 37, macrolides in 31 and statins in 12). Severe disease occurred in 29 (14.7%) patients. After adjustment for confounding factors, immunomodulatory therapies as a group were not associated with a lower risk for developing severe disease (odds ratio [OR] 0.64; 95% confidence interval [CI] 0.22-1.86). In a further a priori analysis, corticosteroids, macrolides and statins were included in a multivariate model. None of these therapies was found to be associated with a lower risk for developing severe disease. Immunomodulatory therapies use since hospital admission did not prevent the development of severe disease in adults with pandemic influenza A (H1N1) 2009 complicated by pneumonia.The Journal of infection 02/2011; 62(3):193-9. · 4.13 Impact Factor
Article: Antibacterial activity of statins: a comparative study of atorvastatin, simvastatin, and rosuvastatin.[show abstract] [hide abstract]
ABSTRACT: Statins have several effects beyond their well-known antihyperlipidemic activity, which include immunomodulatory, antioxidative and anticoagulant effects. In this study, we have tested the possible antimicrobial activity of statins against a range of standard bacterial strains and bacterial clinical isolates. Minimum inhibitory concentrations (MIC) values were evaluated and compared among three members of the statins drug (atorvastatin, simvastatin, and rosuvastatin). It was revealed that statins are able to induce variable degrees of antibacterial activity with atorvastatin, and simvastatin being the more potent than rosuvastatin. Methicillin-sensitive staphylococcus aureus (MSSA), methicillin-resistant staphylococcus aureus (MRSA), vancomycin-susceptible enterococci (VSE), vancomycin-resistant enterococcus (VRE), acinetobacter baumannii, staphylococcus epidermidis, and enterobacter aerogenes, were more sensitive to both atorvastatin, and simvastatin compared to rosuvastatin. On the other hand, escherichia coli, proteus mirabilis, and enterobacter cloacae were more sensitive to atorvastatin compared to both simvastatin and rosuvastatin. Furthermore, most clinical isolates were less sensitive to statins compared to their corresponding standard strains. Our findings might raise the possibility of a potentially important antibacterial class effect for statins especially, atorvastatin and simvastatin.Annals of Clinical Microbiology and Antimicrobials 05/2012; 11:13. · 2.64 Impact Factor