Aclidinium bromide safe for COPD patients regardless of exacerbation history

The LAMA* aclidinium bromide was similarly effective in reducing exacerbation rate without raising the risk of MACE** or all-cause mortality regardless of recent history of exacerbations in patients with moderate-to-very severe chronic obstructive pulmonary disease (COPD), according to a subgroup analysis of the phase IV ASCENT-COPD*** trial presented at the CHEST 2019 Annual Meeting.

These findings are reassuring on the safety of aclidinium bromide in COPD patients with comorbid CV risk factors, in light of concerns about the safety of LAMA in this group of patients, said Professor Robert Wise of Johns Hopkins University School of Medicine, Baltimore, Maryland, US who presented the study.

The phase IV ASCENT-COPD study randomized 3,589 patients with moderate-to-very severe COPD with elevated cardiovascular risk in a 1:1 ratio to receive aclidinium bromide 400 µg twice daily or placebo. In the current subanalysis, patients were stratified based on whether they had ≥1 exacerbation in the previous year (prior exacerbation; mean age 66.9 years, 57.6 percent male) or not (mean age 67.5 years, 60.3 percent male). About 40.4 percent of the patients in the aclidinium bromide group and 39.5 percent in the placebo group did not have prior exacerbations.

Aclidinium bromide reduced exacerbation rate by similar extent regardless of whether they have prior exacerbation (rate ratio [RR], 0.80, 95 percent confidence interval [CI], 0.68–0.94) or not (RR, 0.69, 95 percent CI, 0.54–0.89; p-interaction=0.340). [CHEST 2019;doi:10.1016/j.chest.2019.08.231]

The slightly better relative risk reduction in the subgroup with prior exacerbation than those without was surprising, according to Wise.

Also, the risk of MACE was not raised in patients receiving aclidinium bromide vs placebo in both subgroups with prior exacerbation (4.6 percent vs 5.6 percent; HR, 0.79, 95 percent CI, 0.54–1.16) and those without (2.8 percent vs 2.1 percent, HR 1.27, 95 percent CI, 0.65–2.47; p-interaction=0.233). The primary safety endpoint of MACE was a composite of CV death, myocardial infarction, and stroke.

Similarly, aclidinium bromide did not raise the risk of all-cause mortality, regardless of exacerbation history (9.3 percent vs 8.6 percent; HR, 1.08, 95 percent CI, 0.81–1.43 for patients with prior exacerbation and 2.4 percent vs 3.5 percent; HR, 0.66, 95 percent CI, 0.36–1.22 for those without; p-interaction=0.154).

“In patients with moderate-to-very severe COPD and high CV risk, aclidinium bromide reduced the moderate/severe exacerbation rate vs placebo and did not increase the risk of [MACE and] all-cause mortality regardless of prior exacerbations,” concluded the Wise and colleagues.  

As there has been concern about the safety of LAMA for people with COPD who have comorbidities, the large ASCENT-COPD trial with a 3-year follow-up provides confirmation to some extent that aclidinium bromide is safe in these patients, said experts.