Triple combination COPD therapy lowers risk for cardiopulmonary outcomes

Key takeaways:

• Two doses of budesonide/glycopyrrolate/formoterol fumarate decreased the risk for moderate/severe exacerbations.
• Trials further evaluating this triple therapy’s link to cardiopulmonary outcomes are underway.

SAN DIEGO — Patients with COPD on budesonide/glycopyrrolate/formoterol fumarate had a lower risk for cardiopulmonary outcomes, according to research presented at the American Thoracic Society International Conference.

David Singh

“Patients with COPD are at risk of cardiovascular and pulmonary events,” David Singh, MD, ETHOS study investigator, told Healio. “Just one COPD exacerbation doubles the risk of a heart attack and increases risk of a stroke, hospitalization and cardiopulmonary-related death.

“These findings further demonstrate why COPD should be prioritized and treated with a similar sense of urgency as that given to other chronic illnesses like cardiovascular diseases or lung cancer,” he added.

As Healio previously reported, the rate of moderate/severe COPD exacerbations declined among patients receiving twice-daily triple inhaled therapy combining budesonide, glycopyrrolate and formoterol fumarate (BGF; Breztri Aerosphere, AstraZeneca) compared with patients receiving glycopyrrolate plus formoterol fumarate (GFF) or budesonide plus formoterol fumarate (BFF) in the phase 3, randomized, double-blind, multicenter, parallel-group ETHOS trial.

In a post-hoc analysis of ETHOS, Singh and colleagues evaluated several cardiopulmonary outcomes among patients with moderate to very severe COPD receiving twice-daily BGF consisting of either 320 µg or 160 µg budesonide, 18 µg glycopyrrolate and 9.6 µg formoterol or BFF (320 µg budesonide plus 9.6 µg formoterol) vs. GFF (18 µg glycopyrrolate plus 9.6 µg formoterol).

Researchers only adjusted one of the assessed endpoints for multiplicity (time to moderate/severe COPD exacerbation), so the others are “exploratory in nature.”

The 320 µg BGF group had significant risk reductions for five of seven analyzed endpoints compared with the GFF group. These included:

• time to all-cause mortality (HR = 0.513; 95% CI, 0.327-0.803);
• time to first cardiovascular adverse event of special interest (HR = 0.629; 95% CI, 0.483-0.819);
• time to first cardiac adverse event (HR = 0.603; 95% CI, 0.481-0.756);
• time to first moderate/severe COPD exacerbation (HR = 0.88; 95% CI, 0.807-0.959); and
• time to first severe cardiopulmonary event (HR = 0.802; 95% CI, 0.674-0.953).

“Breztri led to a 20% reduction in risk of severe cardiopulmonary events compared to dual bronchodilator LAMA/LABA in patients with moderate to very severe COPD and a history of exacerbations,” Singh said.

Similar to patients receiving 320 µg BGF, patients receiving 160 µg BGF vs. GFF faced a significant lower risk for time to first cardiovascular adverse event of special interest (HR = 0.737; 95% CI, 0.573-0.948), time to first cardiac adverse event (HR = 0.659; 95% CI, 0.529-0.822) and time to first moderate/severe COPD exacerbation (HR = 0.866; 95% CI, 0.794-0.944).

The only endpoint result that was not significant when comparing 320 µg BGF vs. GFF but was significant when comparing 160 µg BGF vs. GFF was time to first major adverse cardiovascular event (HR = 0.625; 95% CI, 0.393-0.994), according to researchers.

Lastly, between the BFF group and the GFF group, the BFF group had a significant decreased risk for time to first cardiovascular adverse event of special interest (HR = 0.647; 95% CI, 0.497-0.842), time to first cardiac adverse event (HR = 0.64; 95% CI, 0.511-0.801) and time to first major adverse cardiovascular event (HR = 0.499; 95% CI, 0.301-0.826).

Compared with GFF, researchers found significant risk reductions in moderate/severe exacerbations with the two doses of BGF but not with BFF.

“Previous analysis of ETHOS and KRONOS from Breztri’s phase 3 clinical trial program showed that Breztri demonstrates reductions in traditional endpoints, such as moderate or severe exacerbations,” Singh told Healio. “The new post-hoc analysis highlights how Breztri is associated with reducing a broader range of cardiopulmonary outcomes.

“Taken together, the results can help transform treatment goals in COPD,” he added.

When asked about future studies, Singh told Healio a phase 3 trial has already begun.

“On March 13, AstraZeneca announced the initiation of the THARROS phase 3 trial investigating the potential of Breztri to improve cardiopulmonary outcomes in people with COPD,” Singh said. “THARROS is the first-ever prospective trial to investigate the potential of an inhaled triple therapy to reduce cardiopulmonary events, a key driver of mortality, in COPD.”

Additionally, the ATHLOS phase 3 trial is underway, which Singh said will evaluate “the impact of Breztri on integrated cardiopulmonary parameters associated with health status and survival in patients with COPD.”

“By fundamentally shifting the treatment paradigm to a more proactive and preventative approach, we can improve prognosis in COPD for the millions of people affected, helping them live healthier, longer and more active lives,” he added.

References:

• AstraZeneca unveils latest research across key respiratory and immune-mediated diseases at ATS 2024 showcasing strength of its broad pipeline and portfolio. https://www.astrazeneca-us.com/media/press-releases/2024/astrazeneca-unveils-latest-research-across-key-respiratory-and-immune-mediated-diseases-at-ats-2024-showcasing-strength-of-its-broad-pipeline-and-portfolio.html. Published May 1, 2024. Accessed May 6, 2024.
• Singh D, et al. Am J Respir Crit Care Med. 2024;doi:10.1154/ajrccm-conference.2024.209.1_MeetingAbstracts.A1209.