The effect of anti-platelet agents on end organ dysfunction and mortality in community acquired pneumonia: A protocol for a systematic review and meta-analysis

BackgroundCommunity acquired pneumonia (CAP) is a common cause of morbidity and mortality globally. Poor outcomes are driven by maladaptive inflammatory and thrombotic host responses. Effective therapies that modulate host responses are lacking. Anti-platelet medications modulate thrombotic and inflammatory pathways and improve long term outcomes in COVID-19 pneumonia, however, the role of anti-platelets in other etiologies of CAP remains uncertain. MethodsWe will conduct a systematic review and meta-analysis of randomized controlled trials (RCTs) and observational studies including adult patients hospitalized for non-COVID-19 community acquired pneumonia (CAP) investigating the effect of anti-platelets (ASA or P2Y12 inhibitors) vs. control on all-cause mortality. We will search electronic databases including MEDLINE(R) (Epub Ahead of Print and In-Process, In-Data-Review & Other Non-Indexed Citations), Embase, Cochrane Central Register of Controlled Trials (CENTRAL), clinical trial registries (clinicaltrials.gov, International Clinical Trials Registry Platform) and conference abstracts from inception to August 2023. Two blinded reviewers will extract data in parallel from included studies after title and abstract screening and application of eligibility criteria. We will use the Cochrane Risk of Bias tool and Newcastle Ottawa Scale to assess risk of bias and study quality from included studies. The primary meta-analysis will be conducted separately for RCTs and observational studies using Random effect inverse variance model. For observational studies, adjusted mortality estimates will be presented as hazard ratios (HR) or adjusted odds ratios (OR) whenever possible. Heterogeneity will be expressed using the I2 statistic. The evidence will be evaluated using the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) framework. DiscussionThe overall treatment effect and safety of anti-platelets in non-COVID-19 CAP will be summarized. The findings may be used to inform the relevance and potential study design of a future RCT evaluating anti-platelets in CAP. If anti-platelets are shown to be safe and effective, this research is expected to contribute to a new standard of treatment for CAP, and a paradigm shift towards targeting host responses in serious infections. Systematic Review RegistrationThis protocol is reported in accordance with the guidelines produced by PRISMA-P. The protocol was registered with Open Science Framework on January 30, 2024 (DOI https://doi.org/10.17605/OSF.IO/H2G7C)