(P-260) The Effect of Aspirin on COPD: A Methodological Review of the Observational Studies

Background: Chronic obstructive pulmonary disease (COPD) is a progressive lung disease characterized by chronic bronchitis and impaired lung function. Current treatments revolve around symptom relief and the prevention of acute COPD exacerbations that require hospitalizations and increase the risk of mortality. Cardiovascular disease (CVD) is a major co-morbidity in COPD patients and is a predictor of all-cause mortality in these patients. Several treatments for CVD, including statins and beta-blockers, have been studied as potential treatments for COPD. Aspirin has also been discussed as a potential therapeutic agent because of its antiplatelet and anti-inflammatory effects.

Objectives: We performed a critical review of the observational studies reporting on the effects of aspirin in patients with COPD and evaluated the potential for biases in the different study designs and data analyses and classify them according to their nature.

Methods: We carried out a systematic review of the literature and full-texts of potentially eligible studies were reviewed. We only included studies that provided information on the effects of aspirin on mortality or COPD exacerbations. Each publication was critically reviewed for time-related biases, such as immortal time bias, and for other sources of biases. We used a random effects model to pool the study-specific results, stratified according to the type of bias.

Results: We identified 8 observational studies reporting on the effects of aspirin on exacerbation or mortality in patients with COPD, published between 2007 and 2020. All studies reported hazard ratios of exacerbation or mortality lower than 1 with aspirin use, suggesting a beneficial effect of this medication. Our review noted that all studies which assessed mortality or COPD exacerbations as an outcome were affected by biases that tended to exaggerate the effectiveness of aspirin. We classified the biases into three major categories: immortal time bias (2 studies), collider-stratification bias (3 studies) and exposure misclassification (3 studies). Several studies were also potentially subject to residual confounding as no adjustment for markers of COPD severity was performed.

Conclusions: In conclusion, the extent of the biases in the observational studies conducted to date on the effectiveness of aspirin in the treatment of COPD is sufficiently concerning that these studies cannot be used as evidence of this potential benefit. Observational studies with proper design and analysis that avoid these biases are essential before recommending the conduct of randomized controlled trials on this question.