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

Background 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). Methods 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. Results 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. Conclusions 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.

Gastrointestinal Adverse Events after Dual Antiplatelet Therapy: Clopidogrel Is Safer than Ticagrelor, but Prasugrel Data Are Lacking or Inconclusive

“…In general, the addition of P2Y 12 platelet receptor antagonists to aspirin (ASA) has been proven to consistently reduce secondary vascular occlusions [1,2], and myocardial infarctions in particular [3], or even exert a mortality benefit [4,5]. Despite obvious advantages of DAPT, there are a few serious shortcomings of more aggressive antiplatelet strategies, more prominent with prasugrel and ticagrelor, including increased bleeding risks [1,2,3,5,6], cancer [7], infections [8,9], dyspnea [5,10] and ventricular arrests [5,11]. Moreover, while bleeding represents a universal class effect after DAPT, somewhat dependent on the regimen potency, other serious adverse events are agent specific and definitely impact the choice of a particular antiplatelet agent among clopidogrel, prasugrel or ticagrelor.…”

“…Aggressive platelet inhibition with prasugrel disintegrates these benign mechanisms to a much stronger extent than the moderate platelet inhibition seen with clopidogrel treatment and results in the significantly higher cancer rates after prasugrel [7]. This hypothesis is indirectly supported by the emerging evidence of higher infection rates [8,9] and impaired wound healing [20] after DAPT. While chronic therapy with clopidogrel causes weakening of platelet-neutrophil aggregates (infections) and/or platelet-macrophage-collagen interactions (wound healing), prasugrel causes a greater disruption including excess of cancer.…”

Coagulation abnormalities in sepsis

“…84,85 Prior treatment with antiplatelet agents, including clopidogrel, is associated with a favorable length of stay and fewer ICU admissions, even though community-acquired pneumonia appears to be more common among patients taking clopidogrel. 84,100 Later clinical studies also report an association of antiplatelet drug therapy including clopidogrel with favorable outcome in critical illness 85e87 ; however, these results are mainly driven by the large number of patients receiving ASA.…”

Pneumonia as an actual medical problem of the 21th century

“…В метаанализе A.K.Gross et al [31] анализируется роль клопидогрела в развитии пневмонии. Предпо сылкой к этому анализу явилась патогенетическая роль тромбоцитов в гомеостазе человека, в частнос ти в развитии пневмонии.…”