Background: Pneumonia is complicated by high rate of mortality and cardiovascular events (CVEs). The potential benefit of aspirin, which lowers platelet aggregation by inhibition of thromboxane A2 production, is still unclear. The aim of the study was to assess the impact of aspirin on mortality in patients with pneumonia. Methods and Results: Consecutive patients admitted to the University‐Hospital Policlinico Umberto I (Rome, Italy) with community‐onset pneumonia were recruited and prospectively followed up until discharge or death. The primary end point was the occurrence of death up to 30 days after admission; the secondary end point was the intrahospital incidence of nonfatal myocardial infarction and ischemic stroke. One thousand and five patients (age, 74.7±15.1 years) were included in the study: 390 were receiving aspirin (100 mg/day) at the time of hospitalization, whereas 615 patients were aspirin free. During the follow‐up, 16.2% of patients died; among these, 19 (4.9%) were aspirin users and 144 (23.4%; P <0.001) were aspirin nonusers. Overall, nonfatal CVEs occurred in 7% of patients, 8.3% in nonaspirin users, and 4.9% in aspirin users (odds ratio, 1.77; 95% confidence interval, 1.03 to 3.04; P =0.040). The Cox regression analysis showed that pneumonia severity index ( PSI ), severe sepsis, pleural effusion, and PaO ₂ /FiO ₂ ratio <300 negatively influenced survival, whereas aspirin therapy was associated with improved survival. Compared to patients receiving aspirin, the propensity score adjusted analysis confirmed that patients not taking aspirin had a hazard ratio of 2.07 (1.08 to 3.98; P =0.029) for total mortality. Conclusions: This study shows that chronic aspirin use is associated with lower mortality rate within 30 days after hospital admission in a large cohort of patients with pneumonia.

The effect of lipopolysaccharide (LPS) on platelet aggregation is still controversial. We performed in vitro and ex vivo studies in controls and in patients with community-acquired pneumonia (CAP) to assess the effect of LPS on platelet activation (PA). LPS (15–100 pg/ml) significantly increased PA only if combined with sub-threshold concentrations (STC) of collagen or ADP; this effect was associated with increased platelet H₂O₂ production, Nox2 activation, PLA2 phosphorylation, thromboxane (Tx)A₂ and 8-iso-PGF2α-III, and was inhibited by aspirin, TxA2 receptor antagonist or by Toll-like receptor 4 blocking peptide (TLR4bp). Analysis of up-stream signalling potentially responsible for Nox2 and PLA2 activation demonstrated that LPS-mediated PA was associated with phosphorylation of AKT, p38 and p47phox translocation. In 10 consecutive CAP patients serum endotoxins were significantly higher compared to 10 controls (145 [115–187] vs 18 [6–21] pg/ml; p<0.01). Ex vivo study showed that agonist-stimulated platelets were associated with enhanced PA (p<0.01), Toll-like receptor 4 (TLR4) expression (p<0.05), TxA₂ (p<0.01) and 8-iso-PGF2α-III (p<0.01) production in CAP patients compared to controls. The study provides evidence that LPS amplifies the platelet response to common agonists via TLR4-mediated eicosanoid production and suggests LPS as a potential trigger for PA in CAP. Supplementary Material to this article is available online at www.thrombosis-online.com