Cardiovascular effects of beta-agonists in patients with asthma and COPD: a meta-analysis.
BACKGROUND
beta-Adrenergic agonists exert physiologic effects that are the opposite of those of beta-blockers. beta-Blockers are known to reduce morbidity and mortality in patients with cardiac disease. beta(2)-Agonist use in patients with obstructive airway disease has been associated with an increased risk for myocardial infarction, congestive heart failure, cardiac arrest, and acute cardiac death.


OBJECTIVE
To assess the cardiovascular safety of beta(2)-agonist use in patients with obstructive airway disease, defined as asthma or COPD.


METHODS
A meta-analysis of randomized placebo-controlled trials of beta(2)-agonist treatment in patients with obstructive airway disease was performed, to evaluate the short-term effect on heart rate and potassium concentrations, and the long-term effect on adverse cardiovascular events. Longer duration trials were included in the analysis if they reported at least one adverse event. Adverse events included sinus and ventricular tachycardia, syncope, atrial fibrillation, congestive heart failure, myocardial infarction, cardiac arrest, or sudden death.


RESULTS
Thirteen single-dose trials and 20 longer duration trials were included in the study. A single dose of beta(2)-agonist increased the heart rate by 9.12 beats/min (95% confidence interval [CI], 5.32 to 12.92) and reduced the potassium concentration by 0.36 mmol/L (95% CI, 0.18 to 0.54), compared to placebo. For trials lasting from 3 days to 1 year, beta(2)-agonist treatment significantly increased the risk for a cardiovascular event (relative risk [RR], 2.54; 95% CI, 1.59 to 4.05) compared to placebo. The RR for sinus tachycardia alone was 3.06 (95% CI, 1.70 to 5.50), and for all other events it was 1.66 (95% CI, 0.76 to 3.6).


CONCLUSIONS
beta(2)-Agonist use in patients with obstructive airway disease increases the risk for adverse cardiovascular events. The initiation of treatment increases heart rate and reduces potassium concentrations compared to placebo. It could be through these mechanisms, and other effects of beta-adrenergic stimulation, that beta(2)-agonists may precipitate ischemia, congestive heart failure, arrhythmias, and sudden death.
Salpeter
Shelley R
SR
Santa Clara Valley Medical Center, San Jose, CA, USA. salpeter@stanford.edu
Ormiston
Thomas M
TM
Salpeter
Edwin E
EE
D000318:Adrenergic beta-Agonists / Q000009:adverse effects* / Q000627:therapeutic use; D001249:Asthma / Q000175:diagnosis / Q000188:drug therapy* / Q000401:mortality; D002319:Cardiovascular System / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D008297:Male; D029424:Pulmonary Disease, Chronic Obstructive / Q000175:diagnosis / Q000188:drug therapy* / Q000401:mortality; D016032:Randomized Controlled Trials as Topic; D012129:Respiratory Function Tests; D018570:Risk Assessment; D012720:Severity of Illness Index; D015996:Survival Rate
D000318:Adrenergic beta-Agonists