Correlation of Inhaled Long-acting Bronchodilators with Adverse Cardiovascular Outcomes in Patients with Stable COPD: A Bayesian Network Meta-Analysis of Randomized Controlled Trials.

A majority of existing studies have focused on the efficacy of inhaled long-acting bronchodilators (ILABs), such as long-acting muscarinic antagonists (LAMAs) and long-acting beta(2)-agonists (LABAs), and LABAs combined with LAMAs in treating chronic obstructive pulmonary disease (COPD). The current metaanalysis aimed to investigate the correlation of ILABs with specific cardiovascular adverse events (CAEs). Five electronic databases, including PubMed, Embase, Cochrane Library, Scopus, and Web of Science were systematically retrieved. Finally, 16 randomized controlled trials were enrolled into the current meta-analysis. Typically, the efficacy of 3 major classes of drugs (LABAs, LAMAs, and LABAs combined with LAMAs), and 7 specific drugs (including formoterol, glycopyrrolate, indacaterol, olodaterol, Salmeterol, tiotropium, and vilanterol) for 4 CAEs, including myocardial infarction, cardiac failure (CF), ischemic heart disease (IHD), and stroke in stable COPD patients, was examined. All the pooled results were analyzed through the odds ratios (ORs) with the corresponding 95% confidence intervals (CIs). The direct meta-analysis results suggested that LABAs could increase the risk of CF in patients with stable COPD compared with placebo controls (OR 1.70, 95% CI, 1.00-2.90). In addition, network meta-analysis results indicated that LAMAs combined with LABAs would result in an increased risk of CF in patients with stable COPD (OR 2.31, 95% CI, 1.10-5.09). According to the ILABs specific drug analysis, formoterol may potentially have protective effects on IHD compared with placebo controls (OR 0.45, 95% CI, 0.18-1.00). In conclusion, among these 3 kinds of ILABs, including LAMAs, LABAs, and LABAs/LAMAs, for stable COPD patients, LAMAs and LABAs are associated with the least possibility to induce myocardial infarction and stroke, respectively. However, the application of LABAs will probably increase the risk of CF; they should be used with caution for stable COPD patients with CF. In addition, in specific-drug analysis, the use of formoterol can reduce the risk of treatment-related IHD. Nevertheless, more studies on different drug doses are needed in the future to further validate this conclusion.