M. Cazzola et Cf. Donner, Long-acting beta(2) agonists in the management of stable chronic obstructive pulmonary disease, DRUGS, 60(2), 2000, pp. 307-320
Long-acting beta(2) agonist bronchodilators (e.g. formoterol, salmeterol) a
re a new interesting therapeutic option for patients with chronic obstructi
ve pulmonary disease (COPD).
In the short term, both salmeterol and formoterol appear to be more effecti
ve than short-acting beta(2) agonists, and in patients with stable COPD the
y are more effective than anticholinergic agents and theophylline.
Regular treatment of patients with COPD with long-acting beta(2) agonists c
an induce an improvement in the respiratory function and certain aspects of
quality of life. Moreover, salmeterol seems to be better than ipratropium
and theophylline in improving lung function at the recommended doses after
a long term treatment.
Use of combination therapy of a long-acting inhaled beta(2) agonist and an
anticholinergic agent or theophylline in patients with COPD has not been su
fficiently studied. Combination of usual doses of ipratropium or oxitropium
with usual doses of salmeterol or formoterol does not appear to improve pu
lmonary function, but this lack of improvement with the combination should
not, in itself, prevent implementation of further therapeutic steps in pati
ents responsive to an anticholinergic agent and/or salmeterol or formoterol
administered singly.
Neither formoterol nor salmeterol elicit significant cardiovascular effects
in healthy individuals and patients with reversible airway obstruction. Ho
wever adverse cardiac events might occur in patients with COPD with pre-exi
sting cardiac arrhythmias and hypoxaemia if they use long-acting beta(2) ag
onists, although the recommended single dose of salmeterol 50 mu g or formo
terol 12 mu g ensures a relatively higher safety margin than formoterol 24
mu g.
The bronchodilatory effect of long-acting beta(2) agonists seems to be fair
ly stable after regular treatment with these bronchodilators. Moreover, pre
-treatment with a conventional dose of formoterol or salmeterol does not pr
eclude the possibility of inducing further bronchodilation with salbutamol
in patients with partially reversible COPD.
All these findings support the use of long-acting beta(2) agonist bronchodi
lators as first-line bronchodilator therapy for the long term treatment of
airflow obstruction in patients with COPD. However, since physicians must a
lways choose a drug that is highly efficacious, well tolerated and inexpens
ive, the cost-effectiveness analysis in relation to Ether bronchodilators w
ill determine the proper place of long-acting beta(2) agonists in the long
term therapy of stable COPD.