Chest
Volume 110, Issue 1, July 1996, Pages 62-70
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Clinical Investigations: COPD
Extended Therapy With Ipratropium Is Associated With Improved Lung Function in Patients With COPD: A Retrospective Analysis of Data From Seven Clinical Trials

https://doi.org/10.1378/chest.110.1.62Get rights and content

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 ipratropium-treated patients was most marked in ex-smokers (average duration of abstinence, 9 years). Shortterm 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.

Section snippets

Data Reviewed

The data presented in this report include all the clinical trial efficacy data comparing ipratropium with a β-agonist in long-term (90-day) trials. Previous publications based on these studies have addressed the effectiveness of ipratropium as a short-term acute bronchodilator14,15 but have not specifically addressed the effects of extended therapy. The data are derived from the following four drug development programs conducted by Boehringer Ingelheim Pharmaceuticals, Ridgefield, Conn, from

Evaluable Patients

Seven 90-day studies in patients with COPD were conducted with ipratropium. In three studies, medications were administered via nebulizer; in four, medications were administered via metered-dose inhaler. The seven studies included 1,836 patients, 909 of whom were randomized to receive β-agonist and 927 of whom were randomized to receive ipratropium. Seven hundred one of the β-agonist group (77%) and 744 of the ipratropium group (80%) completed the 90 days of study and were available for

DISCUSSION

The current study assessed the effects of 90-day administration of ipratropium compared to β-agonist in patients with COPD. Over the 90-day period, improvements in baseline lung function, as assessed by both FEV1 and FVC, were observed in ipratropium-treated patients. Ipratropium is also an acute bronchodilator, and the lung function achieved after acute bronchodilator was also greater at the end of the treatment period. These effects contrasted with the patients who were treated with

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