Long-acting bronchodilators (LABDs) and major adverse cardiac events (MACE) in patients with COPD: A pooled analysis of 12 randomised trials

Introduction: The cardiovascular (CV) safety of LABDs in COPD patients is a concern due to the high prevalence of CV comorbidities in this population. We evaluated the safety of LABDs in terms of CV risk and mortality in a pooled analysis of randomised trials. Methods: We included 12 randomised clinical trials of 3 to 12 months duration, comparing LABDs with placebo with respect to the time to first MACE and all-cause mortality. A subgroup analysis was performed in patients with history of CV comorbidities (myocardial infarction, ischaemic heart disease, cardiac failure, ischaemic and haemorrhagic CV conditions or cardiac arrhythmia). The hazard ratio (HR) was estimated, adjusted for age, gender, body mass index (BMI), ICS use, COPD severity, hyperlipidaemia, hypertension and diabetes. Results: The pooled data included 10,895 patients (LABDs, n=8,168; placebo, n=2,727). Patient demographics and clinical characteristics were comparable between the groups. Time to first MACE between LABDs vs. placebo (adjusted HR: 0.96; 95% CI, 0.66-1.38; p=0.83) and time to death (adjusted HR: 0.70; 95% CI, 0.37-1.35; p=0.29) were comparable. In the subgroup of 1,121 patients with a history of CV comorbidities (LABDs, n=793; placebo, n=328), the time to first MACE was significantly delayed relative to placebo (adjusted HR: 0.34; 95% CI, 0.18-0.67; p=0.0016). Conclusions: LABDs did not increase the risk of MACE and death in the overall pooled population from the 12 trials. Among patients with a history of CV comorbidities, LABDs were associated with a significantly delayed time to first MACE. Our data further support the safety of LABDs in this high-risk population.