Cardiovascular safety of beta(2)-adrenoceptor agonist use in patients with obstructive airway disease: a systematic review.

BACKGROUND

beta(2)-Adrenoceptor agonists have been used as bronchodilators in the management of asthma and chronic obstructive pulmonary disease (COPD); however, there is evidence suggesting that beta(2)-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 beta(2)-adrenoceptor agonist use in patients with obstructive airway disease, defined as asthma or COPD.

RESULTS

Case-control studies have shown that beta(2)-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 beta(2)-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 beta(2)-adrenoceptor agonists significantly increase heart rate and decrease potassium concentrations compared with placebo.

CONCLUSIONS

Initiation of beta(2)-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 beta-adrenergic stimulation that beta(2)-adrenoceptor agonists may induce ischaemia, congestive heart failure, arrhythmias and sudden cardiac death. In addition to increasing adverse cardiovascular events, beta(2)-adrenoceptor agonist use may induce respiratory tolerance and increase the risk of asthma attacks. It is not clear whether beta(2)-adrenoceptor agonists should be used regularly in the treatment of obstructive airway disease, with or without concomitant cardiovascular disease.