Study designs of evaluations included in the review
Randomised controlled trials (RCTs) were eligible for inclusion.
Specific interventions included in the review
Studies comparing a beta2-agonist (either a single dose or longer duration of treatment) with placebo were eligible for inclusion. Trials were included if they allowed open-label rescue beta2-agonist in both the treatment and placebo groups. The included studies were of formoterol, fenoterol, terbutaline, salmeterol, salbutamol, albuterol, procaterol, levalbuterol and isoproterenol, either alone or in combination. There were studies of single-dose treatment and studies of longer treatment duration (mean 4.7 months, range: 3 days to 1 year). Rescue beta2-agonist use for treatment and placebo groups was permitted in all but one of the included studies.
Participants included in the review
Studies of participants with obstructive airway disease, defined as asthma or chronic obstructive pulmonary disease (COPD), were eligible for inclusion. Apart from one study of both asthma and COPD participants, the included studies were of either asthma or COPD participants alone. The mean age of the participants was 56.6 years in single-dose studies and 52.2 years in studies of longer duration.
Outcomes assessed in the review
Single-dose studies were eligible for inclusion if they provided extractable data on heart rate or potassium concentrations. Longer duration trials were eligible for inclusion if they reported at least one adverse cardiovascular effect. A cardiovascular event was defined as sinus or ventricular tachycardia, atrial fibrillation, syncope, myocardial infarction, congestive heart failure, cardiac arrest, or sudden death. Adverse events such as palpitations, chest pain, hypertension were classified as minor and were not included.
How were decisions on the relevance of primary studies made?
Two investigators independently assessed studies for inclusion. Inter-rater agreement was 98% (95% confidence interval, CI: 96, 100).