Long-Acting Bronchodilator Therapy for the Treatment of Chronic Obstructive Pulmonary Disease

OBJECTIVE: To review clinical data on the use of long-acting bronchodilator agents as monotherapy and in combination for the treatment of moderate-to-severe chronic obstructive pulmonary disease (COPD). DATA SOURCES: A literature search was performed via MEDLINE (1966-April 2008). In addition, references from publications identified were reviewed. These searches were limited to human data published in the English language. Searches used the following terms: COPID, long-acting beta-agonists, long-acting anticholinergics, combination therapy, pharmacoeconomics, safety, tiotropium, salmeterol, and formoterol. STUDY SELECTION AND DATA EXTRACTION: Relevant information on the pharmacology, safety, efficacy, pharmacoeconomics, adherence, and available agents used in the treatment of COPID was selected. Randomized clinical trials and retrospective reviews were included. DATA SYNTHESIS: The Global Initiative for Chronic Obstructive Lung Disease guidelines provide general management recommendations to guide providers regarding treatment choices for COPD; however, they lack clarity regarding which long-acting bronchodilator to use and when combining agents becomes appropriate. Prospective trials evaluating short-acting anticholinergics and long-acting beta(2)-agonists have utilized spirometric endpoints that relate most to short-term symptomatic relief. Tiotropium trials have focused more on patient-oriented outcomes, with data being reported for one year. Tiotropium significantly lowers exacerbation rates and improves health resource usage as well as health-related quality of life. Tiotropium also provides superior bronchodilation and improvement in dyspnea at all time points, although onset of bronchodilation is slower than with long-acting beta(2)-agonists. Combining these agents has been shown to decrease daytime rescue inhaler use, improve morning and evening peak expiratory flow rates, and improve bronchodilator efficacy compared with monotherapy. Pharmacoeconomic data lend support to the recommendation of tiotropium as a first-line long-acting agent. CONCLUSIONS: Tiotropium appears to be the best option as a first-line drug for patients with moderate-to-severe COPID because of its ability to sustain bronchodilator effect, improve quality of life, reduce COPID exacerbations, and reduce health resource usage. Patients who remain symptomatic may benefit from the addition of a long-acting beta(2)-agonist to tiotropium monotherapy.