NEW ORLEANS – A history of recent exacerbations did not significantly affect the safety or efficacy of aclidinium bromide ( ) in patients with moderate to severe chronic obstructive pulmonary disease and high cardiovascular risk, analysis of a postmarketing surveillance trial suggests.
Regardless of exacerbation history, the long-acting muscarinic antagonist reduced the rate of moderate or severe COPD exacerbations versus placebo in this subgroup analysis of the phase IV, presented here at the annual meeting of the American College of Chest Physicians.
At the same time, there were no significant increases in the risk of mortality or major cardiac adverse events (MACE) for those patients who had an exacerbation in the past year versus those who did not, according to investigator.
Those findings may be reassuring, given that COPD patients commonly have comorbidities and cardiovascular risk factors, according to Dr. Wise, professor of medicine at the Johns Hopkins University, Baltimore.
“There’s a concern and some evidence that patients who have a propensity to COPD exacerbations may also have an increased risk for cardiovascular events,” Dr. Wise said in a podium presentation.
Accordingly, he and coinvestigators sought to tease out the impact of COPD exacerbations on safety as well as efficacy in the randomized, placebo-controlled ASCENT-COPD trial, which included 3,630 patients with moderate to severe COPD plus a cardiovascular disease history or multiple atherothrombotic risk factors.
Of the patients who were analyzed in the study, 1,433 patients had at least one treated COPD exacerbation in the year before screening for the study, while 2,156 had no exacerbations in the prior year, Dr. Wise said.
Top-line results of that study, published several months ago, showed that aclidinium did not increase MACE risk over 3 years, and reduced the rate of moderate to severe COPD exacerbations over the first year ().
In this latest analysis, presented at the meeting, risk of MACE with aclidinium treatment was not increased versus placebo, irrespective of whether they had exacerbations in the prior year (interaction P = .233); likewise, the risk of all-cause mortality was similar between groups (P = .154).
In terms of reduction in moderate or severe COPD exacerbations in the first year, aclidinium was superior to placebo both for the patients who had at least one or exacerbation in the prior year (rate ratio, 0.80) and those who had no exacerbations in the prior year (RR, 0.69).
“This translates into a number-needed-to-treat to prevent one exacerbation of about 11 patients for those without an exacerbation, compared to about 6 patients for those with a prior exacerbation,” Dr. Wise said in his presentation.
The ASCENT-COPD study was funded initially by Forest Laboratories and later by AstraZeneca and Circassia. Dr. Wise provided disclosures related to AstraZeneca, GlaxoSmithKline, Boehringer Ingelheim, Sunovion, Mylan/Theravance, Contrafect, Pearl, Merck, Verona, Novartis, AbbVie, Syneos, Regeneron, and Kiniksa.
SOURCE: Wise R et al. CHEST 2019. .