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Published on: August 24, 2019
Cardiovascular mortality and morbidity in chronic obstructive pulmonary disease: the impact of bronchodilator
R Wood-Baker1, B Cochrane, M T Naughton
1Menzies Research Institute, Hobart, Tasmania, Australia. richard.woodbaker@utas.edu.au
Insights
Bronchodilators are generally safe for stable Chronic Obstructive Pulmonary Disease (COPD) patients. However, ipratropium bromide may increase cardiovascular risks, and combining certain bronchodilators in acute settings poses significant cardiovascular risks.
Area of Science:
- Pulmonary Medicine
- Cardiology
- Pharmacology
Background:
- Cardiovascular disease (CVD) is a leading cause of death and frequently coexists with Chronic Obstructive Pulmonary Disease (COPD).
- COPD, both stable and during exacerbations, is linked to increased cardiac arrhythmias.
- Bronchodilator medications are suspected contributors to CVD in COPD patients due to intrinsic effects or side-effects.
Purpose of the Study:
- To evaluate the cardiovascular safety of inhaled bronchodilators in COPD patients.
- To investigate the pro-arrhythmic potential of bronchodilator therapies in COPD.
- To assess the risks associated with combining bronchodilators in acute COPD exacerbations.
Main Methods:
- Review of existing clinical trials and studies on inhaled bronchodilators in COPD.
- Analysis of methodological limitations in previous research, including confounding factors like concomitant medications.
- Focus on therapeutic doses of inhaled formulations and specific drug classes.
Main Results:
- Most bronchodilators at therapeutic levels in stable COPD appear safe.
- Ipratropium bromide shows an association with increased cardiovascular adverse effects.
- Combining short-acting beta-agonists and short-acting anticholinergics in acute settings is linked to increased cardiovascular risk and lacks proven benefit.
Conclusions:
- Current evidence suggests most bronchodilators are safe for stable COPD at therapeutic doses.
- Ipratropium bromide warrants caution due to associated cardiovascular risks.
- Combination therapy with certain bronchodilators in acute COPD exacerbations should be approached with caution due to elevated cardiovascular risk.
Abstract:
Chronic obstructive pulmonary disease (COPD) is a substantial health burden. Cardiovascular disease (CVD), the leading cause of death, frequently coexists with COPD, an effect attributed to high individual disease prevalences and shared risk factors. It has long been recognized that COPD, whether stable or during acute exacerbations, is associated with an excess of cardiac arrhythmias. Bronchodilator medications have been implicated in the excess CVD seen in COPD, either as an intrinsic medication effect or related to side-effects. Despite the theory behind increased pro-arrhythmic effects in COPD, the reported results of trials investigating this for inhaled formulations at therapeutic doses are few. Methodological flaws, retrospective analysis and inadequate adjustment for concomitant medications, including short-acting 'relief' bronchodilators and non-respiratory medications with known arrhythmia propensity, mar many of these studies. For most bronchodilators at therapeutic levels in stable COPD, we can be reassured of their safety from current studies. The exception to this is ipratropium bromide, where the current data indicate an association with increased cardiovascular adverse effects. Moreover, there is no proven benefit from combining short-acting beta-agonists with short-acting anticholinergics at high doses in the acute setting, and although this practice is widespread, it is associated with increased cardiovascular risk.
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