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

A. Kendall Gross, Steven P. Dunn, David J. Feola, Craig Martin, Richard Charnigo, Zhenyu Li, Ahmed Abdel-Latif, Susan S. Smyth

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53 Scopus citations


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.

Original languageEnglish
Pages (from-to)147-154
Number of pages8
JournalJournal of Thrombosis and Thrombolysis
Issue number2
StatePublished - Feb 2013

Bibliographical note

Funding Information:
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.


  • Antiplatelet therapy
  • Clopidogrel
  • Cohort study and meta-analysis
  • Community acquired pneumonia
  • Thienopyridine

ASJC Scopus subject areas

  • Hematology
  • Cardiology and Cardiovascular Medicine


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