Cardiac effects of formoterol and salmeterol in patients suffering from COPD with preexisting cardiac arrhythmias and hypoxemia

Objective: There are several reports of documented adverse cardiac effects during treatment with beta-agonists. Since one should be aware that this may be a problem in patients with preexisting cardiac disorders, we have conducted a randomized, single-blind, balanced, crossover, placebo-controlled study to assess the cardiac effects of two single doses of formoterol (12 mu g and 24 mu g) and one single dose of salmeterol (50 (mu g) in 12 patients suffering from COPD with preexisting cardiac arrhythmias and hypoxemia (PaO2 < 60 mm Hg). Design: Each patient was evaluated at a screening visit that included spirometry, blood gas analysis, plasma potassium measurement, and 12-lead ECG. In following nonconsecutive days, all patients underwent Holter monitoring 24 h during each of the four treatments. Holter monitoring was started soon before drug administration in the morning. Plasma potassium level was measured before drug inhalation, at 2-h intervals for 6 h, and at 9, 12, and 24 h following administration. None of our patients took rescue medication during the 24-h period. Results: Holter monitoring showed a heart rate higher after formoterol, 24 mu g, than after formoterol, 12 mu g, and salmeterol, 50 mu g, and supraventricular or ventricular premature beats more often after formoterol, 24 mu g. Formoterol, 24 mu g, significantly reduced plasma potassium level for 9 h when compared with placebo, whereas formoterol, 12 mu g, was different after 2 h and salmeterol, 50 mu g, from 4 to 6 h. Conclusions: The results of this study suggest that if a COPD patient is suffering from preexisting cardiac arrhythmias and hypoxemia, long-acting beta-agonists may have adverse effects on the myocardium, although the recommended single dose of salmeterol and formoterol, 12 mu g, allows a higher safety margin than formoterol, 24 mu g.