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Clopidogrel treatment and the incidence and severity of community acquired pneumonia in a cohort study and meta-analysis of antiplatelet therapy in pneumonia and critical illness

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Abstract

Platelet activation results in the release and upregulation of mediators responsible for immune cell activation and recruitment, suggesting that platelets play an active role in immunity. Animal models and retrospective data have demonstrated benefit of antiplatelet therapy on inflammatory mediator expression and clinical outcomes. This study sought to characterize effects of clopidogrel on the incidence and severity of community-acquired pneumonia (CAP). A retrospective cohort study was conducted of Kentucky Medicaid patients (2001–2005). The exposed cohort consisted of patients receiving at least six consecutive clopidogrel prescriptions; the non-exposed cohort was comprised of patients not prescribed clopidogrel. Primary endpoints included incidence of CAP and inpatient treatment. Secondary severity endpoints included mortality, intensive care unit admission, mechanical ventilation, sepsis, and acute respiratory distress syndrome/acute lung injury. CAP incidence was significantly greater in the exposed cohort (OR 3.39, 95 % CI 3.27–3.51, p < 0.0001) that remained after adjustment (OR 1.48, 95 % CI 1.41–1.55, p < 0.0001). Inpatient treatment was more common in the exposed cohort (OR 1.96, 95 % CI 1.85–2.07, p < 0.0001), but no significant difference remained after adjustment. Trends favoring the exposed cohort were found for the secondary severity endpoints of mechanical ventilation (p = 0.07) and mortality (p = 0.10). Pooled analysis of published studies supports these findings. While clopidogrel use may be associated with increased CAP incidence, clopidogrel does not appear to increase—and may reduce—its severity among inpatients. Because this study was retrospective and could not quantify all variables (e.g., aspirin use), these findings should be explored prospectively.

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Abbreviations

ADP:

Adenosine diphosphate

ALI:

Acute lung injury

ARDS:

Acute respiratory distress syndrome

CAD:

Coronary artery disease

CAP:

Community acquired pneumonia

CI:

Confidence interval

COPD:

Chronic obstructive pulmonary disease

CURB65:

Confusion, uremia, respiratory rate, low BP, age 65 or greater

HF:

Heart failure

ICU:

Intensive care unit

LPS:

Lipopolysaccharide

OR:

Estimated odds ratio

ORadj:

Estimated adjusted odds ratio

PCV:

Pneumococcal conjugative vaccine

PSI:

Pneumonia severity index

TLR:

Toll-like receptors

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Acknowledgments

A. Kendall Gross, PharmD and Susan S. Smyth, MD, PhD are the guarantors of this manuscript. This work was partially supported by NIH grants HL080166 (SSS) and RR021954 (ZL, SSS). This material is the result of work supported with the resources and/or use of the facilities at the Lexington VA Medical Center. No relationships or financial associations exist with industry that might pose a conflict of interest in connection with this article. The authors would like to acknowledge the contributions of Douglas Steinke, PhD, Jeffery Talbert, PhD, Darren Henderson, and Adam Lindstrom for their assistance with database administration and statistical analyses, and Susan Quick for editorial assistance.

Conflict of interest

None.

Author information

Authors and Affiliations

  1. Pharmaceutical Services, UCSF Medical Center and Clinical Pharmacy, School of Pharmacy, University of California, San Francisco, San Francisco, CA, USA

    A. Kendall Gross

  2. Pharmacy Services, University of Virginia Health System, Charlottesville, VA, USA

    Steven P. Dunn

  3. Pharmacy Practice and Science, College of Pharmacy, University of Kentucky, Lexington, KY, USA

    David J. Feola

  4. Pharmacy Services, UK HealthCare and Pharmacy Practice and Science, College of Pharmacy, University of Kentucky, Lexington, KY, USA

    Craig A. Martin

  5. Department of Biostatistics, College of Public Health, University of Kentucky, Lexington, KY, USA

    Richard Charnigo

  6. Division of Cardiovascular Medicine, Gill Heart Institute, University of Kentucky, 741 S. Limestone Street, 255 BBSRB, Lexington, KY, USA

    Zhenyu Li & Susan S. Smyth

  7. Lexington VA Medical Center and Division of Cardiovascular Medicine, Gill Heart Institute, University of Kentucky, Lexington, KY, USA

    Ahmed Abdel-Latif & Susan S. Smyth

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  1. A. Kendall Gross
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Correspondence to Susan S. Smyth.

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This work was performed at the University of Kentucky.

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Gross, A.K., Dunn, S.P., Feola, D.J. et al. Clopidogrel treatment and the incidence and severity of community acquired pneumonia in a cohort study and meta-analysis of antiplatelet therapy in pneumonia and critical illness. J Thromb Thrombolysis 35, 147–154 (2013). https://doi.org/10.1007/s11239-012-0833-4

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  • DOI: https://doi.org/10.1007/s11239-012-0833-4

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