A44-21 Safety of Gabapentoids in COPD Patients - Effect on Mortality and Respiratory Outcomes

Abstract Background and Summary Over the past decade, growing concerns have emerged regarding the safety of gabapentinoids (gabapentin and pregabalin). Multiple studies and case reports highlighted their association with central nervous system depression, and respiratory failure. In response, the U.S. Food and Drug Administration (FDA) and several European regulatory agencies issued safety warnings in 2019 about the risk of serious respiratory adverse events linked to these neuropathic agents particularly in individuals with pre-existing respiratory risk factors. In our study, we investigated the effect of gabapentoids use in COPD patients on mortality as a primary outcome, as well as hospitalization, acute excacerbation and the need of endotracheal intubation as secondary outcomes. Methods We conducted a retrospective analysis using the TriNetX Global Collaborative Network, which provides de-identified patients electronic health records. Adult patients (≥18 years) with COPD were included. Patients with coexisting asthma were excluded. Two cohorts were formed: those prescribed gabapentoids after COPD diagnosis and those never exposed. We also divided each cohort into 3 subgroups according to COPD severity (Mild, Moderate, severe/very severe) using FEV1 according to the Global Initiative For Obstructive Lung Disease (GOLD) criteria. Propensity score matching (1:1) was performed. Odds ratios (OR) with 95% confidence intervals (CI) were calculated, with p 0.05 considered significant. Results A total of 13887 COPD patients in the gabepentoid arm were divided into 3 subgroups according to COPD severity. Each subgroup was matched into a controlled group. Patients with severe and very severe COPD (FEV1 50%) had a significant increase in all-cause mortality (OR 1.602; 95% CI: 1.175–2.185; p = 0.003), hospitalization (OR 2.039; 95% CI: 1.799–2.310; p 0.0001), acute COPD excacerbations (OR 1.395; 95% CI: 1.169–1.664; p = 0.0002), and need for endotracheal intubation (OR 3.019; 95% CI: 1.473–6.187; p = 0.002) at 30 days. These results persisted at 90 days. Patients with mild (FEV1 80%) and moderate (FEV1 50%-80%) COPD showed similar results during the same time period with the exception of acute excacerbations showing no significant difference. Conclusion In this retrospective cohort study of COPD patients, gabapentoid use was associated with significantly higher short-term mortality, hospitalization, and endotracheal intubation across all patients regardless of their COPD severity. These findings raise concerns about the safety profile of gabapentoids and highlight the need for cautious prescribing and further prospective evaluation to assess their risk profile in this patients population. This abstract is funded by: none