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Background: Community-acquired pneumonia (CAP) triggers inflammatory and thrombotic host responses driving morbidity and mortality. Antiplatelet agents may favorably modulate these pathways; however, their role in non–COVID-19 CAP remains uncertain. Objectives: To evaluate the association of antiplatelet agents with mortality in hospitalized patients with non–COVID-19 CAP. Methods: We conducted a systematic review and meta-analysis of observational studies and randomized controlled trials (RCTs) of adult patients hospitalized for non–COVID-19 CAP exposed to antiplatelet agents (acetylsalicylic acid or P2Y12 inhibitors). We searched MEDLINE, Embase, and CENTRAL from inception to August 2023. Our primary outcome was all-cause mortality: meta-analyzed (random-effects models) separately for observational studies and RCTs. For observational studies, we used adjusted mortality estimates. Results: We included 13 observational studies (123,012 patients; 6 reported adjusted mortality estimates) and 2 RCTs (225 patients; both high risk of bias). In observational studies reporting hazard ratio, antiplatelet agents were associated with lower mortality (hazard ratio, 0.65; 95% CI, 0.46-0.91; I2 = 85%; 4 studies, 91,430 patients). In studies reporting adjusted odds ratio, antiplatelet agent exposure was associated with reduced odds of mortality (odds ratio, 0.67; 95% CI, 0.45-1.00; I2 = 0%; 2 studies, 24,889 patients). Among RCTs, there was a nonsignificant association with mortality (risk ratio, 0.66; 95% CI, 0.20-2.25; I2 = 54%; 2 studies, 225 patients). By the Grading of Recommendations, Assessment, Development, and Evaluation criteria, the certainty of the evidence was low, primarily due to risk of bias. Conclusion: In hospitalized patients with non–COVID-19 CAP, antiplatelet agents may be associated with reduced mortality compared with usual care or placebo, but the certainty of evidence is low. |
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