Extended Therapy With Ipratropium Is Associated With Improved Lung Function in Patients With COPD

A Retrospective Analysis of Data From Seven Clinical Trials

¹ From the Pulmonary and Critical Care Medicine Section, Department of Internal Medicine, University of Nebraska Medical Center, Omaha, Nebraska
² From Boehringer Ingelheim, Ridgefield, Conn
³ From the Department of Pulmonary Diseases and Critical Care Medicine, Tulane University Medical Center, New Orleans

Objective: Bronchodilators are routinely used in the long-term therapy of patients with COPD. These drugs are generally evaluated for their short-term bronchodilatory effects. Long-term and short-term benefits, however, are not necessarily equivalent. We evaluated, therefore, the effects of extended therapy with inhaled bronchodilators in patients with COPD.

Design: Data were obtained from seven clinical trials in which ipratropium was compared with a β-agonist over a 90-day treatment interval. This comprised all the available data from clinical trials performed for registration of ipratropium and included 1,445 evaluable patients. Results of pulmonary function tests were evaluated prior to and after short-term administration of bronchodilator both before and after the 90-day treatment period. In addition, data were analyzed after stratification for smoking status and for lung function.

Results: Long-term therapy with ipratropium resulted in improvement in baseline (ie, before short-term administration of bronchodilator) FEV₁ (28 mL; p<0.01) and FVC (131 mL; p<0.01), while long-term therapy with β-agonist resulted in no significant change in FEV₁ (1-mL decline; p>0.2) or in FVC (20-mL improvement; p>0.2). The improvement in baseline function in the ipratropiumtreated patients was most marked in ex-smokers (average duration of abstinence, 9 years). Short-term administration of ipratropium following the 90-day treatment interval resulted in similar response in average FEV₁ (6 mL more improvement after the extended therapy; p>0.2) and an increased response in average FVC (44 mL more improvement after extended therapy; p<0.01). In contrast, extended therapy with β-agonist resulted in significantly less response to the short-term administration of β-agonist for both FEV₁ (49 mL less response; p<0.0001) and FVC (74 mL less response; p<0.0001). Assessed as the percentage of patients who achieved a 15% improvement in lung function, most patients responded to both treatments both before and after extended therapy. There was, however, a significant decline in the number of patients who responded after extended therapy, and this was more marked for the β-agonist treated group.

Conclusion: Long-term benefits of bronchodilator therapy appear to differ from short-term effects. Extended administration of ipratropium appears to be associated with improved baseline lung function and perhaps with improvement in the response to acute bronchodilation. Extended administration of β-agonist, in contrast, appears to have little effect on baseline lung function, but may decrease response to acute bronchodilation.

Key Words: β-agonist • bronchodilator • COPD • ipratropium • tachyphylaxis

Submitted on July 12, 1995
Accepted on February 15, 1996

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