Chest
Volume 114, Issue 2, August 1998, Pages 411-415
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Clinical Investigations: COPD
Cardiac Effects of Formoterol and Salmeterol in Patients Suffering from COPD with Preexisting Cardiac Arrhythmias and Hypoxemia

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Objective

There are several reports of documented adverse cardiac effects during treatment with β-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 pg and 24 pg) and one single dose of salmeterol (50 pg) 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 pg, than after formoterol, 12 pg, and salmeterol, 50 pg, and supraventricular or ventricular premature beats more often after formoterol, 24 µg. Formoterol, 24 µg, significantly reduced plasma potassium level for 9 h when compared with placebo, whereas formoterol, 12 pg, was different after 2 h and salmeterol, 50 pg, 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 β-agonists may have adverse effects on the myocardium, although the recommended single dose of salmeterol and formoterol, 12 pg, allows a higher safety margin than formoterol, 24 pg.

Section snippets

Materials and Methods

We have conducted a randomized, single-blind, balanced, crossover, placebo-controlled study to assess the cardiac effects of formoterol, 12 μg and 24 and salmeterol, 50 μg, in 12 patients suffering from COPD with preexisting mild-to-moderate cardiac arrhythmias and hypoxemia (PaO2 <60 mm Hg). The study design was approved by an independent ethics committee and each subject gave written informed consent before participation. All patients fulfilled the criteria proposed by the American Thoracic

Results

The mean heart rate for all patients on 4 study days is shown in Figure 1. Formoterol, 24 μg, induced a statistically significant increase when compared with placebo and formoterol, 12 μg, and salmeterol, 50 μg. Both formoterol, 12 μg, and salmeterol, 50 μg, had a significant greater effect than placebo, but there were no differences between these two treatments.

Isolated supraventricular premature beats (SVPBs) were observed in 11 patients after placebo and salmeterol and in 12 patients after

Discussion

Supraventricular and ventricular dysrhythmias, as well as conduction disturbances of varying severity, are frequently observed in COPD patients. The type of arrhythmia that occurs in patients with COPD is influenced by their clinical state. Coexisting coronary heart disease, severe blood gas abnormalities, and medication may precipitate the rhythm disturbances.9 In particular, patients with hypoxemic COPD may have a subclinical autonomic neuropathy that has been associated with a prolonged ECG

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