The cardiovascular safety long-acting β-agonists (LABAs) and long-acting anticholinergics (LAAs [also known as LAMAs]) is currently a matter for debate. It is thought that LABAs suppress parasympathetic control and LAAs stimulate sympathetic control, both leading to an increased risk of tachyarrhythmias, myocardial ischemia, stroke, and death. Evidence to date is conflicting and the available studies have had various limitations.
The purpose of the current study was to clarify the relative cardiovascular risk of LABA compared with LAA in older patients with COPD. Researchers used health administrative data from Ontario and included in the study all patients with COPD who were aged ≥ 66years and who received at least one prescription for a short- or long-acting β-agonist or anticholinergic, an inhaled corticosteroid, or a methylxanthine in the study period (Sep 2003 to March 2009; n=191,005). The primary outcome was hospitalisation or emergency department visit for a cardiovascular event – those experiencing this (n=53,532; 28.0%) were deemed cases and each was matched to one control.
New users of LABAs and LAAs were found to be at an increased risk for the primary outcome (adjusted odds ratio [OR] of 1.31 [95% CI 1.12-1.52; P<0.001] and 1.14 [1.01-1.28; P=0.03]) and this risk was highest in the first 2-3 weeks after the medicine was prescribed. There was no evidence that new users of LABAs were more at risk than new users of LAAs.
The authors comment that this is the first study to compare the cardiovascular safety of LABAs and LAAs directly in a large, inclusive, real-world population of older patients with COPD. They discuss the similar findings of previous studies in this area, but note how their results differ from those of previous RCTs and the possible reasons for this. They acknowledge the study’s limitations; for example confounding cannot be ruled out; there was no clinical detail, so they were unable to rule out a worsening of COPD being mistaken for cardiovascular instability, for example; and COPD may have been misclassified.
Based on their findings, they suggest all patients with COPD who require long-acting bronchodilators should be closely monitored, regardless of drug class.