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

Abstract

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 β2–agonists (LABAs), and LABAs combined with LAMAs in treating chronic obstructive pulmonary disease (COPD). The current meta-analysis 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.

Association between Inhaled β2-agonists Initiation and Risk of Major Adverse Cardiovascular Events: A Population-based Nested Case-Control Study

“…Our findings are consistent with results from a recent meta-analysis of RCTs showing an increased risk of cardiac failure among patients with stable COPD and receiving LABA therapy than patients receiving placebo (odds ratio, OR 1.70, 95% CI, 1.00–2.90). 35 Additional network meta-analysis results indicated that LABAs combined with LAMAs resulted in an increased risk of cardiac failure in patients with COPD compared with placebo (OR 2.32, 95% CI, 1.10–5.09). 35 Also, in another meta-analysis of 43 randomized trials, the authors reported that inhaled LABA increased the risk of cardiac failure (relative risk [RR] 1.71, 95% CI 1.04–2.84, I 2 27.5%).…”

“… 35 Additional network meta-analysis results indicated that LABAs combined with LAMAs resulted in an increased risk of cardiac failure in patients with COPD compared with placebo (OR 2.32, 95% CI, 1.10–5.09). 35 Also, in another meta-analysis of 43 randomized trials, the authors reported that inhaled LABA increased the risk of cardiac failure (relative risk [RR] 1.71, 95% CI 1.04–2.84, I 2 27.5%). 36 Furthermore, a recent nested-case control study indicated that new use of LABAs or LAMAs in patients with COPD is associated with an approximately 1.5-fold increase in severe cardiovascular risk, irrespective of prior CVD status and history of exacerbation.…”

Biochemical Behaviours of Salmeterol/Fluticasone Propionate in Treating Asthma and Chronic Obstructive Pulmonary Diseases (COPD)

“…Paradoxical bronchospasm, laryngeal spasm, and swelling of the throat may occur. Long-acting beta-agonists (LABAs) increase the risk of heart failure in people with COPD [ 20 ].…”

The Potential Synergistic Risk of Albuterol and Vasoactives in Acute Lung Injury Trials

“…Similarly, a meta-analysis showed that bronchodilator therapy increased the risk of heart failure in patients with stable COPD compared with placebo controls suggesting this long-term treatment needs to be used with caution in patients with or without cardiac conditions. 16 In this study, concomitant therapy was not associated with increased cardiac adverse events in patients with ALI and this could be due to the relative sample size.…”