Article type
Year
Abstract
Objectives: To critically examine, using best evidence synthesis methodology, the use of long acting ?2-agonist (salmeterol and formoterol) agents versus placebo and anticholinergics with or without short acting ?2-agonist agents, for the maintenance treatment of chronic stable COPD. Before starting the study, the trend in utilization of long acting ?2-agonists and ipratropium bromide was evaluated using data supplied by Intercontinental Medical Statistics (IMS).
Methods: Published and unpublished literature was obtained by searching multiple databases (from January 1974 to December 2001) , hand searching selected journals,documents and the bibliographies of selected papers, and by contacting manufacturers. All published and unpublished prospective studies of 34 wk duration, of both parallel and crossover design, were included in the review if they included patients with (a) FEV1 75% or less than predicted, and FEV1/FVC less than 70% predicted; and (b) less than 15% reversibility of FEV1 after a dose of a short acting ?2-agonist. Two independent reviewers undertook the decisions for inclusion of studies and assessment of trial quality. Two reviewers independently extracted data- including FEV1, peak expiratory flow rates (PEFR), six minute walk test, quality of life, dyspnoea measurements, number of exacerbations and rescue salbutamol use.
Results: According to IMS data from 1996 to 2001, the recommended use of salmeterol and formoterol for COPD increased 1150% and 1975%, respectively, while recommendations for ipratropium bromide for COPD decreased by 37%. Our systematic review identified 64 potentially relevant studies, with 8 studies satisfying our inclusion criteria. Five studies compared salmeterol and placebo, two-compared salmeterol, ipratropium bromide and placebo, and one compared formoterol, theophylline and placebo. A quality assessment of these studies by the Jadad scale showed that five were of moderate quality (quality scores: 3) and three were of low quality (quality scores: 2). None of the outcome measure data were suitable for pooling. Compared to placebo, salmeterol significantly increased in FEV1 (absolute value) in four studies and formoterol significantly increased FEV1 compared to placebo in one study. A significant decrease with salmeterol compared to placebo was observed in additional day time night time rescue bronchodilator in two studies. No significant improvements in PEFR, distance traveled in a 6 min walk test, transition dyspnea index (TDI) scores or incidence of exacerbation of COPD were observed with salmeterol versus placebo in any of the studies. Studies comparing salmeterol and ipratropium bromide did not show any significant difference in improving FEV1 and TDI scores.
Conclusion: Although utilization of long acting ?2-agonists for the treatment of COPD has increased exponentially in the last 6 years, evidence of their superiority over traditional agents like ipratropium bromide is still lacking. The high cost of long acting ?2agonists compared to ipratropium bromide suggests that long acting ?2-agonists might be best used as second line agents for treatment of COPD.
Methods: Published and unpublished literature was obtained by searching multiple databases (from January 1974 to December 2001) , hand searching selected journals,documents and the bibliographies of selected papers, and by contacting manufacturers. All published and unpublished prospective studies of 34 wk duration, of both parallel and crossover design, were included in the review if they included patients with (a) FEV1 75% or less than predicted, and FEV1/FVC less than 70% predicted; and (b) less than 15% reversibility of FEV1 after a dose of a short acting ?2-agonist. Two independent reviewers undertook the decisions for inclusion of studies and assessment of trial quality. Two reviewers independently extracted data- including FEV1, peak expiratory flow rates (PEFR), six minute walk test, quality of life, dyspnoea measurements, number of exacerbations and rescue salbutamol use.
Results: According to IMS data from 1996 to 2001, the recommended use of salmeterol and formoterol for COPD increased 1150% and 1975%, respectively, while recommendations for ipratropium bromide for COPD decreased by 37%. Our systematic review identified 64 potentially relevant studies, with 8 studies satisfying our inclusion criteria. Five studies compared salmeterol and placebo, two-compared salmeterol, ipratropium bromide and placebo, and one compared formoterol, theophylline and placebo. A quality assessment of these studies by the Jadad scale showed that five were of moderate quality (quality scores: 3) and three were of low quality (quality scores: 2). None of the outcome measure data were suitable for pooling. Compared to placebo, salmeterol significantly increased in FEV1 (absolute value) in four studies and formoterol significantly increased FEV1 compared to placebo in one study. A significant decrease with salmeterol compared to placebo was observed in additional day time night time rescue bronchodilator in two studies. No significant improvements in PEFR, distance traveled in a 6 min walk test, transition dyspnea index (TDI) scores or incidence of exacerbation of COPD were observed with salmeterol versus placebo in any of the studies. Studies comparing salmeterol and ipratropium bromide did not show any significant difference in improving FEV1 and TDI scores.
Conclusion: Although utilization of long acting ?2-agonists for the treatment of COPD has increased exponentially in the last 6 years, evidence of their superiority over traditional agents like ipratropium bromide is still lacking. The high cost of long acting ?2agonists compared to ipratropium bromide suggests that long acting ?2-agonists might be best used as second line agents for treatment of COPD.