Efficacy and Safety of an Aclidinium Bromide Treatment for 12 Weeks or Longer in Patients with Moderate-To-Severe COPD: A Meta-Analysis

This guideline is an official statement of the American College of Physicians (ACP), American College of Chest Physicians (ACCP), American Thoracic Society (ATS), and European Respiratory Society (ERS). It represents an update of the 2007 ACP clinical practice guideline on diagnosis and management of stable chronic obstructive pulmonary disease (COPD) and is intended for clinicians who manage patients with COPD. This guideline addresses the value of history and physical examination for predicting airflow obstruction; the value of spirometry for screening or diagnosis of COPD; and COPD management strategies, specifically evaluation of various inhaled therapies (anticholinergics, long-acting β-agonists, and corticosteroids), pulmonary rehabilitation programs, and supplemental oxygen therapy. This guideline is based on a targeted literature update from March 2007 to December 2009 to evaluate the evidence and update the 2007 ACP clinical practice guideline on diagnosis and management of stable COPD. RECOMMENDATION 1: ACP, ACCP, ATS, and ERS recommend that spirometry should be obtained to diagnose airflow obstruction in patients with respiratory symptoms (Grade: strong recommendation, moderate-quality evidence). Spirometry should not be used to screen for airflow obstruction in individuals without respiratory symptoms (Grade: strong recommendation, moderate-quality evidence). RECOMMENDATION 2: For stable COPD patients with respiratory symptoms and FEV(1) between 60% and 80% predicted, ACP, ACCP, ATS, and ERS suggest that treatment with inhaled bronchodilators may be used (Grade: weak recommendation, low-quality evidence). RECOMMENDATION 3: For stable COPD patients with respiratory symptoms and FEV(1) 50% predicted. (Grade: weak recommendation, moderate-quality evidence). RECOMMENDATION 7: ACP, ACCP, ATS, and ERS recommend that clinicians should prescribe continuous oxygen therapy in patients with COPD who have severe resting hypoxemia (Pao(2) ≤55 mm Hg or Spo(2) ≤88%) (Grade: strong recommendation, moderate-quality evidence).

The efficacy and safety of two doses of aclidinium bromide were evaluated in patients with moderate to severe chronic obstructive pulmonary disease (COPD). In this 24-week, double-blind trial, patients were randomised to twice-daily aclidinium (200 μg or 400 μg) or placebo. The primary efficacy end-point was change in trough forced expiratory volume in 1 s (FEV(1)) at week 24. Other end-points included peak FEV(1), health status (St George's Respiratory Questionnaire; SGRQ) and dyspnoea (Transitional Dyspnoea Index; TDI). Overall, 828 patients were randomised. At week 24, significant improvements from baseline were observed with aclidinium 200 μg and 400 μg versus placebo for trough FEV(1) (99 and 128 mL; both p<0.0001) and peak FEV(1) (185 and 209 mL; both p<0.0001). Peak FEV(1) improvements on day 1 were comparable with week 24. Aclidinium 200 μg and 400 μg produced significant improvements over placebo in baseline-adjusted mean SGRQ total score (-3.8 and -4.6 units; p<0.001 and p<0.0001) and TDI focal score (0.6 and 1.0 units; p<0.05 and p<0.001) at week 24. With both aclidinium doses, the incidence of anticholinergic adverse events was low, and similar to placebo. Twice-daily aclidinium significantly improved bronchodilation, health status and dyspnoea, and was well tolerated in patients with COPD.