B24-11 Exacerbation Outcomes With Revefenacin in COPD Patients With Cardiovascular Risk or History: Exploratory Analyses From Study 0128

Background Cardiovascular (CV) comorbidities are prevalent in patients with COPD and are associated with heightened risk of acute exacerbations of COPD (AECOPDs) and mortality. Preventing exacerbations in this population is critical, as AECOPDs increase subsequent CV event risk. We explored the impact of once-daily nebulized revefenacin (REV), a long-acting muscarinic antagonist, on AECOPD risk in COPD patients with CV risk or history. Methods Study 0128 was a 52-week, randomized, open-label, active-controlled, safety trial comparing REV 175 mcg with tiotropium (TIO) in patients with moderate-to-very-severe COPD. An ad hoc logistic regression analysis was conducted in the safety analysis set (all dosed patients, n = 1,055), assessing predictors of treatment-emergent AECOPDs, with specific focus on CV risk factors and ischemic heart disease history. Candidate predictors (e.g., prior exacerbations, smoking status, baseline symptoms) were screened (p < 0.1), and treatment assignment was added to the final multivariable model. AECOPD rates were compared by treatment group for patients with versus without CV history/risk factors. Results Across the safety analysis set, 280 patients (27%) experienced ≥1 AECOPD. Treatment with REV versus TIO was associated with reduced odds of experiencing ≥1 AECOPD (OR 0.67; 95% CI: 0.46, 0.97). In patients with CV risk factors or ischemic heart disease, REV did not increase exacerbation risk relative to TIO. Rates of moderate/severe AECOPDs showed a consistent trend favoring REV, though hospitalization events were too few (35 events in 32 patients) for inference. Baseline characteristics and risk factor distributions were well balanced across treatment groups. Conclusions Exploratory analyses from Study 0128 suggest that revefenacin does not increase, and may reduce, the risk of COPD exacerbations compared with tiotropium, including in patients with CV risk or history. These findings reinforce the importance of exacerbation prevention in COPD subgroups with CV comorbidity.