title: 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.
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.
authors.affiliation: Pharmaceutical Services, UCSF Medical Center and Clinical Pharmacy, School of Pharmacy, University of California, San Francisco, San Francisco, CA, USA. kendall.gross@ucsfmedctr.org
authors.forename: A Kendall
authors.initials: AK
authors.lastname: Gross
authors.forename: Steven P
authors.initials: SP
authors.lastname: Dunn
authors.forename: David J
authors.initials: DJ
authors.lastname: Feola
authors.forename: Craig A
authors.initials: CA
authors.lastname: Martin
authors.forename: Richard
authors.initials: R
authors.lastname: Charnigo
authors.forename: Zhenyu
authors.initials: Z
authors.lastname: Li
authors.forename: Ahmed
authors.initials: A
authors.lastname: Abdel-Latif
authors.forename: Susan S
authors.initials: SS
authors.lastname: Smyth
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000077144:Clopidogrel; D015331:Cohort Studies; D017714:Community-Acquired Infections / Q000175:diagnosis / Q000188:drug therapy / Q000453:epidemiology; D016638:Critical Illness / Q000453:epidemiology* / Q000628:therapy; D016208:Databases, Factual; D005260:Female; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use*; D011014:Pneumonia / Q000175:diagnosis / Q000188:drug therapy* / Q000453:epidemiology*; D012720:Severity of Illness Index; D013988:Ticlopidine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D010975:Platelet Aggregation Inhibitors; D000077144:Clopidogrel; D013988:Ticlopidine