Abstract
BackgroundWhile inhaled bronchodilators reduce symptoms and acute exacerbations of chronic obstructive pulmonary disease (COPD), their use is associated with increased cardiovascular events in some studies. This study investigates the risk of adverse events associated with the use of inhaled bronchodilators in COPD patients with multimorbidity.MethodsA case-control study was conducted between January 2015 and December 2017, and patients with spirometry-confirmed diagnosis of COPD (N = 1565) using inhaled long-acting bronchodilators were enrolled. Medical records were reviewed and clinical data, including age, gender, smoking status, major comorbidities, lung function stage, history of exacerbations, bronchodilator regimens, and treatment duration were analyzed. Major adverse cardiovascular events occurring during long-acting bronchodilator use were recorded.ResultsThe most common comorbidities were cardiovascular disease (CVD) (53.6%) and chronic kidney disease (CKD) (25.8%). We observed that CVD (odds ratio [OR], 5.77), CKD (OR, 2.02) and history of frequent exacerbations (OR, 2.37) were independent risk factors for cardiovascular events, regardless of the type of bronchodilators use. Moreover, COPD patients with both CKD and CVD had higher risk (6.32-fold) of adverse cardiovascular effects than those with neither comorbidity. Eighty-seven of 1565 (5.56%) COPD patients died during this study period. Of them, 21.8% (19/87) were cardiovascular-related and 73.6% (64/87) patients were respiratory-related mortality. Among COPD patients using long-acting bronchodilators, CKD was the only risk factor to predict cardiovascular events and cardiovascular-related mortality (OR, 4.87; 95% confidence interval [CI], 1.75–13.55].ConclusionsCOPD patients had higher risk of cardiovascular events were associated with their CVD and/or CKD comorbidities and history of frequent exacerbations, rather than associated with their use of inhaled bronchodilators.
Highlights
While inhaled bronchodilators reduce symptoms and acute exacerbations of chronic obstructive pulmonary disease (COPD), their use is associated with increased cardiovascular events in some studies
Majority of patients (n = 1185, 75.7%) exposed to only one inhaler, 254 (16.2%) patients exposed to two kinds of inhalers, 104 (6.6%) patients exposed to three kinds of inhalers and 22 (1.4%) patients exposed to 4 kinds of inhalers
We classified the patients into different groups (LAMA, Long-acting β2-agonists (LABA), LABA/long-acting muscarinic antagonists (LAMA), inhaled corticosteroids (ICS)/LABA or triple therapy) according to the inhalers they were prescribed more than 30 days and recorded the events under the inhalers use
Summary
While inhaled bronchodilators reduce symptoms and acute exacerbations of chronic obstructive pulmonary disease (COPD), their use is associated with increased cardiovascular events in some studies. This study investigates the risk of adverse events associated with the use of inhaled bronchodilators in COPD patients with multimorbidity. The clinical efficacy of inhaled bronchodilators has been demonstrated in clinical trials as quality of life improvement, prevention of lung function decline, and reduction of acute exacerbation frequency. Renal impairment is a common comorbidity in elderly COPD patients [11, 12] who may be at higher risk of adverse events due to decreased elimination and increased systemic effects of long-acting bronchodilators [13,14,15]. In large clinical trials, COPD patients with significant renal impairment or cardiac disease were usually excluded from the studies [16,17,18], the safety issue of COPD patient with significant renal or cardiovascular disease using long-acting bronchodilators is still being debated [9, 10, 15, 16, 19,20,21]
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