Ref (type)	Population	Outcome, Interventions	Results and statistical analysis	Effect size	Favours
Adverse effects
[31] Systematic review	2404 people with COPD 4 RCTs in this analysis	Mortality attributed to treatment-related respiratory problems 21/1320 (2%) with long-acting beta2 agonist 8/1084 (1%) with placebo	RR 2.47 95% CI 1.12 to 5.45 P = 0.03	Moderate effect size	placebo
[30] Systematic review	5055 people 12 RCTs in this analysis	Proportion of people who withdrew because of an adverse effect with long-acting beta2 agonists with placebo Absolute results not reported	OR 0.86 95% CI 0.72 to 1.02 P = 0.09		Not significant
[34] RCT	657 people with COPD	Rate of adverse effects (rates/1000 treatment days) 6 months 3.8 with formoterol 9 micrograms twice daily 4.5 with placebo	Significance not assessed
[35] RCT 4-armed trial	6184 people with COPD; 6112 people included in efficacy analysis	Proportion of people experiencing a drug-related adverse effect 12% with salmeterol (50 micrograms twice daily) 13% with placebo Absolute numbers not reported	Significance not assessed
[27] Systematic review	15,276 people with asthma or COPD 22 RCTs in this analysis	Adverse cardiovascular events with beta2 agonists (short- and long-acting) with placebo Absolute results not reported	RR 2.54 95% CI 1.59 to 4.05	Moderate effect size	placebo
[27] Systematic review	386 people with asthma or COPD 11 RCTs in this analysis	Increased heart rate with beta2 agonists (single dose of either short- or long-acting) with placebo Absolute results not reported	WMD 9.12 95% CI 5.32 to 12.92	Effect size not calculated	placebo
[40] RCT 5-armed trial	1465 people with COPD	Heart rate difference from baseline 12 weeks –2.4 bpm with arformoterol 15 micrograms twice daily –0.6 bpm with arformoterol 25 micrograms twice daily –0.3 bpm with arformoterol 50 micrograms once daily –0.0 bpm with salmeterol 42 micrograms twice daily –1.8 bpm with placebo	P >0.05 for any active treatment v placebo		Not significant
[41] RCT 3-armed trial	351 people with COPD	Arrhythmia 12 weeks with formoterol 20 micrograms nebulised twice daily with formoterol 12 micrograms dry powder twice daily with placebo Absolute numbers not reported	P >0.05 for either dose of formoterol v placebo		Not significant
[27] Systematic review	168 people with asthma or COPD 6 RCTs in this analysis	Reduction in serum potassium concentration with beta2 agonists (single dose of either short- or long-acting) with placebo Absolute results not reported	WMD –0.36 95% CI –0.54 to –0.18	Effect size not calculated	placebo