Aclidinium does not increase MACE risk in patients with COPD and heart disease: JAMA

DELHI: In patients with chronic obstructive pulmonary disease (COPD) and increased cardiovascular risk, aclidinium, a long-acting muscarinic antagonist (LAMA), is noninferior to placebo for risk of MACE (major adverse cardiovascular events) over 3 years. It also reduced the rate of COPD exacerbations over the first year.

These are the results of a recent study published in the Journal of the American Medical Association.

There is a concern that long-acting muscarinic antagonists increase cardiovascular morbidity or mortality in patients with COPD. Robert A. Wise, Johns Hopkins University School of Medicine, Baltimore, Maryland, and colleagues conducted this study to determine the cardiovascular safety (noninferiority) and efficacy (superiority) of aclidinium bromide, 400 μg twice daily, in patients with COPD and cardiovascular disease or risk factors.

Multicenter, randomized, placebo-controlled, double-blind, parallel-design study was conducted across 522 sites in North America. In which, a total of 3630 patients with moderate to very severe COPD and either a history of cardiovascular disease or at least 2 atherothrombotic risk factors were randomized to receive aclidinium (n = 1812) or placebo (n = 1818) by dry-powder inhaler, twice daily for up to 3 years.

The primary safety endpoint was time to the first MACE over up to 3 years. The primary efficacy endpoint was the annual COPD exacerbation rate during the first year of treatment.

Also Read: FDA approves Duaklir inhaler for maintenance treatment of COPD

The researchers found that:

• Among 3589 patients analyzed (mean age, 67.2 years; 58.7% male), 2537 (70.7%) completed the study.


• Of these, 69 (3.9%) aclidinium and 76 (4.2%) placebo patients had a MACE; the expanded MACE definition included 168 (9.4%) aclidinium vs 160 (8.9%) placebo patients with events.


• Annual moderate to severe exacerbation rates (aclidinium, 0.44; placebo, 0.57) and rate of exacerbations requiring hospitalization (aclidinium, 0.07; placebo, 0.10) decreased significantly with aclidinium vs placebo.


• The most common adverse events were pneumonia (aclidinium, 109 events [6.1%]; placebo, 105 events [5.8%]), urinary tract infection (aclidinium, 93 events [5.2%]; placebo, 89 events [5.0%]), and upper respiratory tract infection (aclidinium, 86 events [4.8%]; placebo, 101 events [5.6%]).

Also Read: Azithromycin reduces treatment failure in acute exacerbations of COPD, finds clinical trial

“By enrolling patients with increased cardiovascular risk and continuing the study until an adequate number of adjudicated MACE had occurred, the study demonstrated that aclidinium was noninferior to placebo with respect to the risk of a new MACE,” concluded the researchers.

For complete study log on to doi:10.1001/jama.2019.4973