- Note that this study was published as an abstract and presented at a conference. These data and conclusions should be considered to be preliminary until published in a peer-reviewed journal.
SAN DIEGO -- Treatment with a long-acting muscarinic antagonist (LAMA) was not associated with major adverse cardiovascular events in chronic obstructive pulmonary disease (COPD) patients with multiple heart disease risk factors, researchers reported here.
Patients with moderate to severe COPD treated with the LAMA aclidinium bromide (Tudorza Pressair) as a maintenance therapy had fewer exacerbations and associated hospitalizations than patients receiving standard treatment without the LAMA (placebo group), according to Robert A. Wise, MD, of Johns Hopkins University School of Medicine in Baltimore, and colleagues.
However, risk for cardiovascular death, non-fatal MI, or non-fatal stroke was similar between the two groups, they reported in a presentation at the American Thoracic Society annual meeting.
"Aclidinium bromide did not increase the risk of major adverse cardiovascular events in patients who had significant cardiovascular risk factors," Wise stated. Cardiovascular safety was a major endpoint of the study.
Add-on treatment with inhaled long-acting bronchodilators, such as LAMAs, is widely recommended, but several studies have suggested that LAMAs may increase the risk of cardiovascular events, Wise explained.
The randomized, double-blind, placebo-controlled study included data on 3,589 patients recruited from 452 treatment centers in the U.S. and Canada.
Wise's group evaluated the long-term effects of aclidinium bromide 400 µg twice daily on safety and exacerbations in patients with moderate to very severe COPD and a history of cerebrovascular, coronary, or peripheral artery disease, or the presence of ≥2 cardiovascular risk factors
The primary safety and efficacy variables were time to first major cardiovascular event (MACE) -- cardiovascular event, non-fatal MI, or non-fatal stroke -- and rate of moderate to severe COPD exacerbations during the first year of treatment.
Per protocol, the study was terminated after ≥122 MACE had occurred (with a maximum study duration of 3 years) in order to achieve 90% power to rule out a hazard ratio of 1.8 in time to first MACE for aclidinium versus placebo.
Non-inferiority was concluded if the upper bound of the 95% confidence interval was <1.8.
A total of 1,791 patients were randomized to the aclidinium bromide arm of the study, and 1,798 received placebo, with 2,084 (58.1%) completing the first year of the study on treatment.
The mean patient age was 67.2, 58.7% were male, and the mean post-bronchodilator forced expiratory volume in 1 second (FEV1) was 47.7% predicted.
Almost two-thirds (63%) of patients were receiving concomitant long-acting β2-agonist (LABA, 6.3%) or LABA/inhaled corticosteroid (56.3%).
Wise reported that there was no increased risk of MACE, or of MACE or other serious cardiovascular events of interest, with aclidinium versus placebo (HR 0.89, P=0.469 and HR 1.03, P=0.772, respectively). The upper bound 95% CI excluded 1.8 for both endpoints.
There was a 22% reduction in moderate to severe exacerbation rate with aclidinium versus placebo (P<0.001), and a 35% reduction in hospitalizations (P<0.01) due to COPD exacerbation during the first year of treatment.
The incidence of adverse events was comparable between groups.
Linda Nici, MD, of Brown University and Provence VA Medical Center in Providence, Rhode Island, said while there has been more concern about cardiovascular risk with LABAs, the LAMA data is reassuring.
In 2010, the FDA warned against use of single-agent LABA products in patients with asthma, because studies had indicated an increase in mortality risk. But that warning did not apply to LABAs used to treat COPD, and no formal warnings of any kind are in place for LAMA drugs.
Nici, who was not involved in the study, said clinicians treating patients with COPD-asthma overlap may be especially wary of LABA/LAMA therapies.
"In the general COPD population, we haven't really thought of LAMAs as a big cardiovascular safety concern, but many patients also have asthma, so I can see where it might be," she told MedPage Today.
The study was funded by AstraZeneca.