IN CHRONIC OBSTRUCTIVE PULMONARY-DISEASE, A COMBINATION OF IPRATROPIUM AND ALBUTEROL IS MORE EFFECTIVE THAN EITHER AGENT ALONE - AN 85-DAY MULTICENTER TRIAL

Combination bronchodilator therapy for chronic obstructive pulmonary d isease (COPD) is available widely throughout the world except in North America. Previous studies have yielded conflicting results regarding the advantages of combining anticholinergic therapy with sympathomimet ic therapy in COPD. We report the results of a 12-week prospective, do uble-blind, parallel-group evaluation of the use of the following: alb uterol, a beta-adrenergic agent; ipratropium, an anticholinergic agent ; or a combination of the two, administered by metered-dose inhaler to patients with moderately severe stable COPD. Following baseline studi es, 534 patients were given one of the three test bronchodilator prepa rations to be used at home four times daily in addition to oral theoph ylline and corticosteroids as required. The doses of the latter two dr ugs were kept stable. Subjects were tested on days 1, 29, 57, and 85. Analysis of l-s forced expiratory volume (FEV(1)) curves on those test days indicated that the combination was superior to either single age nt alone in peak effect, in the effect during the first 4 h after dosi ng, and in the total area under the curve of the FEV(1) response. The mean peak percent increases in FEV(1) over baseline on the four test d ays were 31 to 33 percent for the combination, 24 to 25 percent for ip ratropium, and 24 to 27 percent for albuterol. The differences between the combination and its components were statistically significant on all test days. The AUC(0-4) means for the combination were 21 to 44 pe rcent greater than the ipratropium means and 30 to 46 percent greater than the albuterol means. Similar changes were noted in the forced vit al capacity curves. Symptom scores did not change over time and did no t differ among the treatment groups. We conclude that the combination of ipratropium and albuterol, when given by metered-dose inhaler to pa tients with COPD, is more effective than either of the two agents alon e. The advantage of the combination is apparent primarily during the f irst 4 h after administration. The availability of combination therapy by metered-dose inhaler should help to improve patient compliance.