Risk of Hospitalized Cardiovascular Events Associated with LAMA/LABA/ICS FDC versus LABA/ICS FDC in Patients with Chronic Obstructive Pulmonary Disease: A Nationwide Cohort Study.

Background: Clinical trial data showed a potential, albeit conflicting, higher cardiovascular risk associated with an inhaled triple therapy of long-acting muscarinic antagonists, long-acting β2 agonists, and inhaled corticosteroids (LAMA/LABA/ICS) versus LABA/ICS in patients with chronic obstructive pulmonary disease (COPD). Evidence from routine care environments remains scant. We sought to assess cardiovascular safety profiles of LAMA/LABA/ICS versus LABA/ICS, targeting fixed-dose combination (FDC) single inhalers. Methods: This cohort study conducted in a nationwide Taiwanese database recruited patients with COPD who received LAMA/LABA/ICS FDC or LABA/ICS FDC between 2019/1/1 and 2022/12/31. We applied Cox regression models with variable-ratio propensity score (PS) matching to compare hospitalized cardiovascular events, including acute myocardial infarction, unstable angina, ischemic stroke, heart failure, and cardiac dysrhythmia, between the treatment groups. Results: A total of 28,851 patients (n=5,836 for LAMA/LABA/ICS FDC and n=23,015 for LABA/ICS FDC) were included in the PS-matched cohort. The hazard ratio (HR) of composite cardiovascular events comparing LAMA/LABA/ICS FDC to LABA/ICS FDC was 1.00 (95% confidence interval [CI], 0.78-1.28) and the results did not materially change for individual outcomes. There was also no increased risk associated with LAMA/LABA/ICS FDC in patients having prior hospitalized cardiovascular episodes (HR, 0.86; 95% CI, 0.62-1.20), having prior hospitalized COPD exacerbations (HR, 0.93; 95% CI, 0.62-1.39), or receiving treatment longer than one year (HR, 0.76; 95% CI, 0.38-1.54). Conclusion: This Taiwanese cohort study did not find a higher risk of various cardiovascular outcomes comparing LAMA/LABA/ICS FDC versus LABA/ICS FDC in patients with COPD, even in high-risk subpopulations.