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Understanding the potential role of statins in pneumonia and sepsis*

Yende, Sachin MD, MS; Milbrandt, Eric B. MD, MPH; Kellum, John A. MD; Kong, Lan PhD; Delude, Russell L. PhD; Weissfeld, Lisa A. PhD; Angus, Derek C. MD, MPH

doi: 10.1097/CCM.0b013e31821b8290
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Objective: To examine the association of statin use with clinical outcomes and circulating biomarkers in community-acquired pneumonia and sepsis.

Design: Multicenter inception cohort study.

Setting: Emergency departments of 28 U.S. hospitals.

Patients: A total of 1895 subjects hospitalized with community-acquired pneumonia.

Interventions: None.

Measurements and Main Results: Our approach consisted of two different comparison cohorts, each reflecting methods used in prior publications in this area. We first compared subjects with prior statin use (prior use cohort), defined as a history of statin use in the week before admission, with those with no prior use. We then compared prior statin users whose statins were continued inhospital (continued use cohort) with those with either no prior use or no inhospital use. We adjusted for patient characteristics, including demographics, comorbid conditions, and illness severity, and accounted for healthy user effect and indication bias using propensity analysis. We determined risk of severe sepsis and 90-day mortality. We measured markers inflammation (tumor necrosis factor, interleukin-6, interleukin-10), coagulation (antithrombin, factor IX, plasminogen activator inhibitor, d-dimer, thrombin antithrombin complex), and lymphocyte cell surface protein expression during the first week of hospitalization. There were no differences in severe sepsis risk between statin users and nonusers for prior (30.8% vs. 30.7%, p = .98) or continued statin use (30.2% vs. 30.8%, p = .85) in univariate analyses and after adjusting for patient characteristics and propensity for statin use. Ninety-day mortality was similar in prior statin users (9.2% vs. 12.0%, p = .11) and lower in continued statin users (7.9% vs. 12.1%, p = .02). After adjusting for patient characteristics and propensity for statin use, there was no mortality benefit for prior (odds ratio, 0.90 [0.63–1.29]; p = .57) or continued statin use (odds ratio, 0.73 [0.47–1.13]; p = .15). Only antithrombin activity over time was higher in statin subjects, yet the magnitude of the difference was modest. There were no differences in other coagulation, inflammatory, or lymphocyte cell surface markers.

Conclusions: We found no evidence of a protective effect for statin use on clinical outcomes and only modest differences in circulating biomarkers in community-acquired pneumonia, perhaps as a result of healthy user effects and indication bias.

From the CRISMA Laboratory (Clinical Research, Investigation, and Systems Modeling of Acute Illness) (SY, EBM, JAK, RLD, DCA), Department of Critical Care Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA; and the Department of Biostatistics (LK, LAW), University of Pittsburgh Graduate School of Public Health, Pittsburgh, PA.

This study was funded by the National Institutes of Health. GenIMS was funded by NIGMS R01GM61992 with additional support from GlaxoSmithKline for enrollment, clinical data collection, and coagulation assays and from Diagnostic Products Corporation and BRAHMS Diagnostica for the cytokine assays.

Drs. Yende and Milbrandt were supported by grants K23GM083215 and K23HL078760 from the National Institutes of Health.

The authors have not disclosed any potential conflicts of interest.

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© 2011 by the Society of Critical Care Medicine and Lippincott Williams & Wilkins