Comparison of three combined pharmacological approaches with tiotropium monotherapy in stable moderate to severe COPD: A systematic review

Background: Guidelines recommend the use of inhaled long-acting bronchodilators, inhaled corticosteroids (ICS) and their combinations for maintenance treatment of moderate to severe COPD. However, there are limited data supporting combination therapy. Methods: This systematic review assessed the efficacy of three therapeutic approaches: tiotropium plus long-acting beta2-agonist (LABA) (" dual" therapy), LABA/ICS (" combined" therapy), and tiotropium plus LABA/ICS (" triple" therapy), all compared with tiotropium monotherapy. Randomized controlled trials were identified after a search of different databases of published and unpublished trials. Results: Twenty trials (6803 participants) were included. "Dual" therapy showed significant improvements in forced volume in the first second (FEV 1), health-related quality of life (HRQoL), and dyspnea. However, it failed to reduce the risk of COPD exacerbations. Compared with tiotropium, " combined" therapy presented modest but significant effects on FEV 1, HRQoL, and dyspnea. Again, there was no significant difference in exacerbations, but it was associated with a significant increase of serious adverse effects (SAE) (number need to treat for harm [NNTH]=20; 95% CI: 11-119). Finally, " triple therapy" increased FEV 1, improved HRQoL (both benefits exceeded minimal important differences) and decrease COPD exacerbations in anon-significant way. (Odds ratio [OR]=0.57; 95% CI: 0.24 to 1.37, p=0.21). Conclusions: " Dual" and " triple" therapy seem like the most promising for patients with moderate to very severe COPD. However, data are still scarce and studies too short to generate a strong recommendation. Future studies should examine long-term efficacy and safety. © 2011 Elsevier Ltd.