Cardiovascular events in patients with COPD after long-acting bronchodilator initiation

Background Real-world evidence concerning the cardiovascular (CV) risk of umeclidinium (UMEC) monotherapy or UMEC/vilanterol (VI) is scarce. This real-world study investigated CV risk in new users of UMEC or UMEC/VI versus new users of tiotropium (TIO) in patients with chronic obstructive pulmonary disease (COPD). Methods This prospective, observational, multinational, cohort study enrolled patients ≥18 years with COPD who initiated UMEC, UMEC/VI or TIO between 2 February 2016 and 31 January 2023. Non-inferiority (95% confidence interval [CI] upper bound <2.0) of UMEC and UMEC/VI to TIO was compared for the time-to-first event (hazard ratio [HR] over 24 months) of a composite CV endpoint of myocardial infarction, stroke, heart failure or sudden cardiac death. Stabilised inverse probability of treatment weighting adjusted for differences in baseline covariate balance between groups. Incidence rates for the composite CV endpoint were calculated. Results In total, 6606 patients were enrolled; 6165 were included in the analysis. Both UMEC (n=1246) and UMEC/VI (n=2448) were non-inferior to TIO (n=2471) for the risk of the composite CV endpoint (adjusted HR [95% CI]: UMEC versus TIO: 1.254 [0.830–1.896]; UMEC/VI versus TIO: 1.352 [0.952–1.922]). Unadjusted composite CV incidence rates were low across cohorts (incidence rate [95% CI] per 100 person-years: UMEC: 1.157 [0.814–1.594]; UMEC/VI: 1.287 [1.034–1.584]; TIO: 0.924 [0.716–1.174]). Conclusions Both UMEC and UMEC/VI were non-inferior to TIO for composite CV risk, suggesting that physicians may consider escalating patients to dual bronchodilator therapy if COPD symptoms are not effectively managed with monotherapy.