, compared with placebo, in a randomized trial of more than 3,000 patients.
Dr. Robert A. Wise
Aclidinium, a long-acting muscarinic antagonist (LAMA), has been shown to reduce COPD exacerbation in the short term, but long-term effectiveness has not been examined, wrote Robert A. Wise, MD, of Johns Hopkins University, Baltimore, and colleagues.
ASCENT-COPD is a multicenter, double-blind, randomized, placebo-controlled, parallel-group noninferiority study conducted at 522 sites in the United States and Canada. A paper on recent data from ASCENT-COPD, published in JAMA, supports early findings reported last year at the American Thoracic Society meeting.
The researchers randomized adults with COPD to a 400-mg dose of aclidinium bromide twice daily, or placebo. The average age of the patients was 67 years; 59% were men. The median exposure time to aclidinium or placebo was 365 days during the first year of treatment, and the median exposure overall was 495 days for aclidinium patients and 478 days for placebo patients.
Of the 2,537 patients who completed the study, 69 (3.9%) in the aclidinium group and 76 (4.2%) in the placebo group experienced a major adverse cardiovascular event (MACE, defined as a composite of cardiovascular death, nonfatal myocardial infarction, and nonfatal stroke).
In addition, annual rates of moderate to severe COPD exacerbations were significantly lower in the aclidinium patients compared with placebo patients (0.44 vs. 0.57, P less than .001).
In a secondary analysis with a definition of MACE expanded to include heart failure, arrhythmias, or cerebrovascular disease, results remained similar between the groups; events occurred in 168 aclidinium patients (9.4%) and 160 placebo patients (8.9%). The rate of COPD exacerbations requiring hospitalization was significantly lower in aclidinium patients, compared with placebo patients (0.07 vs. 0.10, P = .006).
Overall, the most common treatment-emergent adverse events were similar in the aclidinium and placebo groups, respectively; pneumonia (6.1% vs. 5.8%), urinary tract infections (5.2% vs. 5.0%), and upper respiratory tract infections (4.8% vs. 5.6%). The most common serious adverse events (in at least 1% of patients) were pneumonia, atrial fibrillation, heart failure, and coronary artery disease. Dry mouth and urinary retention were rare, and occurred in less than 1% of patients in each group.
“No patient subgroup demonstrated a difference in efficacy except when analyzed by baseline COPD severity, in which the treatment benefit was observed only in patients with FEV1 [forced expiratory volume in 1 second] of 50% predicted or less,” the researchers noted. “This may be explained by the lower exacerbation rate seen in the placebo group in patients with moderate airway obstruction vs. severe or very severe obstruction,” they said.
“Outcomes of this trial add data to the long-standing controversy over the safety of LAMAs in COPD” and support the need for additional research, they said.
The study findings were limited by several factors including insufficient power to detect cause-specific mortality and the use of a LAMA with low risk of systemic effects, the researchers noted.
SOURCE: Wise R et al. JAMA. 2019. 321:1693-1701.