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Cardiovascular Safety of β2-Adrenoceptor Agonist Use in Patients with Obstructive Airway Disease

A Systematic Review

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Abstract

Background

β2-Adrenoceptor agonists have been used as bronchodilators in the management of asthma and chronic obstructive pulmonary disease (COPD); however, there is evidence suggesting that β2-adrenoceptor agonist use may increase morbidity and mortality.

Methods

A systematic review of case-control studies and randomised controlled trials was performed to evaluate the cardiovascular safety of β2-adrenoceptor agonist use in patients with obstructive airway disease, defined as asthma or COPD.

Results

Case-control studies have shown that β2-adrenoceptor agonist use is associated with an increased risk of myocardial infarction, congestive heart failure, cardiac arrest and sudden cardiac death. The degree of risk appears to be dose-dependent, and may be highest for new users and those with concomitant cardiac conditions. Pooled data from randomised placebo-controlled trials indicate that β2-adrenoceptor agonist use increases the risk of adverse cardiovascular events by more than 2-fold compared with placebo, thus providing evidence that the association seen in case-control studies is a causal one. Single doses of β2-adrenoceptor agonists significantly increase heart rate and decrease potassium concentrations compared with placebo.

Conclusions

Initiation of β2-adrenoceptor agonist treatment increases heart rate and decreases potassium concentrations, while continued use may increase the risk of adverse cardiovascular events. It could be through these effects of β-adrenergic stimulation that β2-adrenoceptor agonists may induce ischaemia, congestive heart failure, arrhythmias and sudden cardiac death. In addition to increasing adverse cardiovascular events, β2-adrenoceptor agonist use may induce respiratory tolerance and increase the risk of asthma attacks. It is not clear whether β2-adrenoceptor agonists should be used regularly in the treatment of obstructive airway disease, with or without concomitant cardiovascular disease.

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Acknowledgements

Financial support was received from the Santa Clara Valley Medical Center to assist in conducting this study. The author has reported no potential conflicts of interest directly relevant to the content of this study.

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Salpeter, S.R. Cardiovascular Safety of β2-Adrenoceptor Agonist Use in Patients with Obstructive Airway Disease. Drugs Aging 21, 405–414 (2004). https://doi.org/10.2165/00002512-200421060-00005

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