Incidence of adverse events (AEs), cardiac AEs and cerebrovascular AEs in the safety population
| Aclidinium/formoterol 400/12 µg twice daily | Salmeterol/fluticasone 50/500 µg twice daily | |
| Patients | 467 | 466 |
| ≥1 AE | 235 (50.3%) | 265 (56.9%) |
| ≥1 SAE | 35 (7.5%) | 33 (7.1%) |
| AEs reported for ≥2% of patients | ||
| COPD exacerbation | 80 (17.1%) | 83 (17.8%) |
| Headache | 28 (6.0%) | 32 (6.9%) |
| Nasopharyngitis | 26 (5.6%) | 28 (6.0%) |
| AEs leading to study discontinuation# | 26 (5.6%) | 34 (7.3%) |
| ICS-related AEs of interest¶ | ||
| Any event | 20 (4.3%) | 50 (10.7%) |
| Lower respiratory and lung infections | 7 (1.5%) | 21 (4.5%) |
| Bronchitis | 5 (1.1%) | 6 (1.3%) |
| Pneumonia | 3 (0.6%) | 9 (1.9%) |
| Anticholinergic-related AEs¶ | ||
| Any event | 17 (3.6%) | 44 (9.4%) |
| Oropharyngeal pain | 6 (1.3%) | 9 (1.9%) |
| Pharyngitis | 0 | 9 (1.9%) |
| Dysphonia | 2 (0.4%) | 6 (1.3%) |
| β2-agonist-related AEs¶ | ||
| Any event | 69 (14.8%) | 76 (16.3%) |
| Headache | 28 (6.0%) | 32 (6.9%) |
| Hypertension | 12 (2.6%) | 10 (2.1%) |
| Muscle spasms | 7 (1.5%) | 11 (2.4%) |
| Any cardiac event | 15 (3.2%) | 15 (3.2%) |
| Serious cardiac events | 4 (0.9%) | 2 (0.4%) |
| Cerebrovascular events | 2 (0.4%) | 2 (0.4%) |
| Serious cerebrovascular events | 2 (0.4%) | 2 (0.4%) |
| MACE composite+ | 4 (0.9%) | 3 (0.6%) |
SAE: serious adverse event; COPD: chronic obstructive pulmonary disease; ICS: inhaled corticosteroid; MACE: major adverse cardiovascular events. #: includes patients who withdrew due to disease progression after reporting this as an AE; ¶: data reported for all events plus the three most common events; +: including cardiovascular death, nonfatal myocardial infarction and nonfatal stroke.