The potential side effects of ICS therapy are often cited as a reason for using long-acting β2-agonists with low-dose ICS rather than trying a higher dose of ICS monotherapy. However, β2-agonists, as for all drugs, are not free from side effects. In particular, a potential problem with the use of β2-agonists in patients with asthma is an increased risk of cardiovascular events.31 Salpeter et al31 performed a metaanalysis of randomized, placebo-controlled trials of β2-agonist treatment in patients with COPD or asthma to evaluate the cardiovascular effects of these agents. A total of 13 single-dose trials and 20 longer-term studies were included in the analysis. A single dose of β2-agonist increased heart rate by 9.12 beats/min (95% confidence interval [CI], 5.32 to 12.92) and reduced potassium concentration by 0.36 mmol/L (95% CI, 0.18 to 0.54) compared with placebo. The long-term effect on adverse cardiovascular events was also investigated (sinus and ventricular tachycardia, syncope, atrial fibrillation, congestive heart failure, myocardial infarction, cardiac arrest, or sudden death). For trials lasting from 3 days to 1 year, β2-agonist treatment significantly increased the relative risk (RR) for a cardiovascular event (RR, 2.54; 95% CI, 1.59 to 4.05) vs placebo. For sinus tachycardia alone, the RR was 3.06 (95% CI, 1.70 to 5.50); for all other events, the RR was 1.66 (95% CI, 0.76 to 3.6). The authors,31 concluded that β2-agonists increase the risk of cardiovascular events in patients with COPD and asthma, and this is of particular concern in patients with underlying cardiac conditions.