Concurrent use of long-acting bronchodilators in COPD and the risk of adverse cardiovascular events

The cardiovascular risk of concurrently using long-acting β₂-agonists (LABAs) and anticholinergics (LAMAs) in COPD is uncertain. We assessed the comparative cardiovascular and cerebrovascular safety of adding a second long-acting bronchodilator in patients with COPD.We identified a cohort of COPD patients, new users of LABA or the LAMA tiotropium during 2002-2012, from the UK Clinical Practice Research Datalink. Using high-dimensional propensity scores, each patient adding a second bronchodilator was matched with a patient who remained on monotherapy. Patients were followed for 1 year for the occurrence of acute myocardial infarction (AMI), stroke, heart failure and arrhythmia.The cohorts included up to 31 174 patients adding a bronchodilator matched to 31 174 patients remaining on bronchodilator monotherapy. Adding a long-acting bronchodilator, compared to remaining on monotherapy, was not associated with an increased risk of AMI (hazard ratio (HR) 1.12, 95% CI 0.92-1.36), stroke (HR 0.87, 95% CI 0.69-1.10) or arrhythmia (HR 1.05, 95% CI 0.81-1.36), but the risk was elevated for heart failure (HR 1.16, 95% CI 1.03-1.30).Adding a second long-acting bronchodilator in the real-world-setting treatment of COPD does not increase the risk of most cardiovascular events. The modest increase for heart failure warrants further investigation.