Aclidinium safe, beneficial in COPD patients with, without prior exacerbations
NEW ORLEANS — In a subgroup analysis of the ASCENT-COPD trial, treatment with the long-acting antimuscarinic bronchodilator aclidinium bromide reduced the risk for new exacerbations compared with placebo in patients with moderate to very severe COPD and high cardiovascular risk, regardless of prior exacerbations.
Further, the data highlight equivalent safety in terms of major adverse CV events and mortality, Robert Wise, MD, FCCP, professor of medicine at Johns Hopkins University School of Medicine, told Healio Pulmonology.
ASCENT-COPD is a phase 4, double-blind, parallel-group study that compared twice-daily aclidinium bromide 400 µg (Tudorza, AstraZeneca and Circassia) with placebo and looked at time to first MACE over up to 3 years and annual COPD exacerbation rate during the first year of treatment. As previously reported in Healio Pulmonology, aclidinium did not increase risk for MACE and decreased exacerbations compared with placebo in this patient population.
The new subgroup analysis investigated outcomes in patients both with and without exacerbations in the previous year.
“Therefore, the finding that there was a similar risk reduction in those with and without exacerbations is an important and novel finding and perhaps surprising to some,” Wise said in a press release.
At the CHEST Annual Meeting, Wise presented data from 3,589 patients; of those, 59.6% of patients assigned aclidinium and 60.5% assigned placebo had at least one exacerbation in the previous year. The mean age was 67 years and more than half were men. The predicted mean post-bronchodilator FEV1 was 45.7% in patients with previous exacerbations and 50.7% in those without exacerbations.
According to the results, rates of exacerbations and the percentage of patients with MACE and all-cause mortality were numerically higher among patients with at least one exacerbation vs. those with no exacerbations. Treatment with aclidinium reduced the exacerbation rate compared with placebo in both groups, with similar benefit (rate ratio = 0.8; 95% CI, 0.68-0.94 in the group with at least one exacerbation and RR = 0.69; 95% CI, 0.54-0.98 in the group with no exacerbations; P for interaction = .34).
With regard to safety, aclidinium treatment did not significantly increase risk for MACE — which included a composite of CV death, nonfatal MI and nonfatal stroke — compared with placebo in either group. In the group with at least one previous exacerbation, MACE occurred in 4.6% of the aclidinium group vs. 5.6% of the placebo group (HR = 0.79; 95% CI, 0.54-1.16) and in the group with no exacerbations, MACE occurred in 2.8% vs. 2.1%, respectively (HR = 1.27; 95% CI, 0.65-2.47; P for interaction = .233), according to the new data. In addition, risk for all-cause mortality was not increased with aclidinium. In the group with at least one previous exacerbation, all-cause mortality occurred in 9.3% of the aclidinium group vs. 8.6% of the placebo group (HR = 1.08; 95% CI, 0.81-1.43) and in the group with no exacerbations, all-cause mortality occurred in 2.4% vs. 3.5%, respectively (HR = 0.66; 95% CI, 0.36-1.22; P for interaction = 1.54).
Wise told Healio Pulmonology these findings are reassuring.
“There has been controversy over the cardiovascular safety of long-acting bronchodilators in patients with COPD,” he said.
Discussing the take-home message of this new analysis, Wise said that “the most important point is that aclidinium reduces exacerbations, whether someone has had one or not.” – by Katie Kalvaitis
Wise R. COPD: Reducing Exacerbations and Improving Treatment Outcomes. Presented at: CHEST Annual Meeting; Oct. 19-23, 2019; New Orleans.
Disclosures: The study was initially funded by Forest Laboratories and later funded by AstraZeneca and Circassia. Wise reports he is an advisory committee member for AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline, Mylan/Theravance, Novartis, Regeneron and Sunovion, consults for AbbVie, Contrafect, GlaxoSmithKline, Kiniksa, Merck, Syneos and Verona, and receives grant/research support from GlaxoSmithKline and Pearl.