Risk of Cardiovascular Events Associated with Inhaled Corticosteroid Treatment in Patients with Chronic Obstructive Pulmonary Disease: A Meta-Analysis

Abstract

Background The cardiovascular (CV) safety of inhaled corticosteroids (ICSs) in chronic obstructive pulmonary disease (COPD) is controversial because different studies have suggested that ICSs either increase or reduce the risk of CV events in COPD patients. In this meta-analysis, we assess the CV safety of ICS therapy in COPD. Methods A meta-analysis of randomized, double-blind, parallel-group, placebo-controlled trials of ICS treatment for COPD that include at least 4 weeks of follow-up was performed. A random-effects model was used to evaluate the effects of ICS treatment on CV events. CV events were documented in each trial, and the relative risk (RR) and 95% confidence intervals (CIs) for ICSs were estimated. Results Thirty-one trials were included in this meta-analysis. The risk of CV events was not different between ICS-treated and control groups (RR: 0.99; 95% CI: 0.93 to 1.06; P=0.801). In a subgroup analysis, there were no significant differences in CV events between an ICS combined with long-acting β2 agonist (LABA) (ICS + LABA) group and an LABA-only group (RR: 1.00; 95% CI: 0.90 to 1.10; P=0.930), as well as between a combination group (ICS + LABA) and a long-acting muscarinic antagonist (LAMA) combined with LABA (LAMA + LABA) group (RR: 0.78; 95% CI: 0.39 to 1.55; P=0.473). In addition, there was no difference in the risk of CV events between ICS treatment and control groups (RR: 0.99; 95% CI: 0.90 to 1.09; P=0.872). Conclusions These results demonstrate that ICSs do not increase the risk of CV events in COPD patients.

Cardiovascular safety of mometasone/indacaterol and mometasone/indacaterol/glycopyrronium once-daily fixed-dose combinations in asthma: pooled analysis of phase 3 trials

“…Comparisons 3a and 3b (ICS-dose effects) and Comparisons 4a and 4b (intra-class effects) did not reveal any differences in the adverse event frequencies between the comparison groups, beyond those expected to arise by chance (Table 4). Results from the ICS-dose comparisons are consistent with findings from a meta-analysis of 31 trials in COPD, where the frequency of cardiovascular events was not different between the ICS-treated and control groups (risk ratio = 0.99; 95% CI: 0.93 to 1.06) [29]. Intra-class effects are also not expected based on data external to the present clinical development program.…”

Inhaled Corticosteroids and Risk of Cardiovascular Disease in Chronic Obstructive Pulmonary Disease: A Systematic Review and Meta-Regression

“…Our findings contradict the findings of a previous metaanalysis by Xia Jing et al 6 The previous meta-analysis found no increased risk of cardiovascular events in COPD patients on ICS-containing medications compared with controls.…”

“…A metaanalysis of 31 RCTs, with at least 4 weeks of follow-up, found no association between ICSs (in any combination) and CVD (relative risk 0.99, 95% confidence interval [CI] 0.90 to 1.90). 6 An additional systematic review published in 2009 included both RCTs and observational studies and found no association between ICSs and CVD in RCTs (relative risk 1.02, 95% CI 0.81 to 1.27), however, in 2 observational studies a protective effect of ICSs was seen on CVD mortality (relative risk 0.79, 95% CI 0.72 to 0.86). 7 This systematic review, however, was published in 2009 and there have been many more observational studies and RCTs published since then.…”

Association between inhaled corticosteroids and upper respiratory tract infection in patients with chronic obstructive pulmonary disease: a meta-analysis of randomized controlled trials

“…Daily use of ICSs has been proved to decrease the frequency of exacerbations and improve quality of life in patients with FEV 1 less than 50% predicted [ 1 , 4 ]. However, daily use of ICSs may cause drug-related adverse events, such as increased risks of fracture and infections [ 32 , 33 ], but may not increase the risk of cardiovascular events [ 34 ]. URTI is the most common respiratory infections and also an important cause of exacerbation of COPD.…”