TY - JOUR
T1 - The impact of exacerbation history on the safety and efficacy of aclidinium in patients with chronic obstructive pulmonary disease and increased cardiovascular risk
T2 - Ascent-copd trial
AU - Wise, Robert A.
AU - Chapman, Kenneth R.
AU - Scirica, Benjamin M.
AU - Daoud, Sami Z.
AU - Lythgoe, Dan
AU - Garcia-Gil, Esther
N1 - Funding Information:
Editorial support, under the direction of the authors, was provided by Richard Knight, PhD, and Sarah Hoyle, PhD, CMC Connect, McCann Health Medical Communications, and funded by AstraZeneca in accordance with Good Publication Practice (GPP3) guidelines (Ann Intern Med. 2015;163:461-464).The ASCENT-COPD study was initially funded by Forest Laboratories and later funded by AstraZeneca and Circassia. AstraZeneca was involved in data collection and interpretation, and the development and review of this manuscript. The decision to submit the manuscript for publication was made by the authors.
Publisher Copyright:
© 2021 Wise et al.
PY - 2021
Y1 - 2021
N2 - Purpose: Chronic obstructive pulmonary disease (COPD) exacerbations are associated with increased risk of major adverse cardiovascular events (MACE) and mortality. Here, we investigate whether the safety and efficacy of aclidinium bromide differ due to exacerbation history in patients with COPD and increased cardiovascular risk. Patients and Methods: ASCENT-COPD was a Phase 4, multicenter, double-blind, rando-mized, placebo-controlled, parallel-group study of patients with moderate-to-very severe COPD and increased cardiovascular risk. Patients were randomized 1:1 to receive aclidinium or placebo twice daily for up to 3 years. Outcomes included time to first MACE and all-cause mortality over 3 years, exacerbation rate during the first year on-treatment, and change in baseline pre-dose forced expiratory volume in 1 second (FEV1) over 3 years. This pre-specified subgroup analysis compared outcomes in patients receiving aclidinium vs placebo. The comparison of patients with vs without an exacerbation history was added following a protocol amendment to increase enrollment in the primary study. Results: Of 3589 patients, 2156 (60.1%) had ≥1 moderate or severe exacerbations in the prior year, compared with 1433 (39.9%) without prior exacerbations. Although patients with an exacerbation history had numerically higher rates of MACE and mortality regardless of treatment, aclidinium did not increase risk of MACE (≥1: hazard ratio [HR] 0.79, 95% confidence interval [CI]: 0.54–1.16; none: HR 1.27, 95% CI: 0.65–2.47; interaction P=0.233) or all-cause mortality (≥1: HR 1.08, 95% CI: 0.81–1.43; none: HR 0.66, 95% CI: 0.36–1.22; interaction P=0.154), regardless of exacerbation history. Aclidinium reduced the exacerbation rate vs placebo irrespective of exacerbation history (≥1: rate ratio [RR] 0.80, 95% CI: 0.68–0.94; none: RR 0.69, 95% CI: 0.54–0.89; interaction P=0.340) and improved FEV1 (interaction P=0.633). Conclusion: In patients with moderate-to-very severe COPD and increased cardiovascular risk, aclidinium did not increase risk of MACE or mortality and reduced exacerbation rate vs placebo, regardless of exacerbation history. Clinical Trial Registration: ClinicalTrials.gov Identifier: NCT01966107.
AB - Purpose: Chronic obstructive pulmonary disease (COPD) exacerbations are associated with increased risk of major adverse cardiovascular events (MACE) and mortality. Here, we investigate whether the safety and efficacy of aclidinium bromide differ due to exacerbation history in patients with COPD and increased cardiovascular risk. Patients and Methods: ASCENT-COPD was a Phase 4, multicenter, double-blind, rando-mized, placebo-controlled, parallel-group study of patients with moderate-to-very severe COPD and increased cardiovascular risk. Patients were randomized 1:1 to receive aclidinium or placebo twice daily for up to 3 years. Outcomes included time to first MACE and all-cause mortality over 3 years, exacerbation rate during the first year on-treatment, and change in baseline pre-dose forced expiratory volume in 1 second (FEV1) over 3 years. This pre-specified subgroup analysis compared outcomes in patients receiving aclidinium vs placebo. The comparison of patients with vs without an exacerbation history was added following a protocol amendment to increase enrollment in the primary study. Results: Of 3589 patients, 2156 (60.1%) had ≥1 moderate or severe exacerbations in the prior year, compared with 1433 (39.9%) without prior exacerbations. Although patients with an exacerbation history had numerically higher rates of MACE and mortality regardless of treatment, aclidinium did not increase risk of MACE (≥1: hazard ratio [HR] 0.79, 95% confidence interval [CI]: 0.54–1.16; none: HR 1.27, 95% CI: 0.65–2.47; interaction P=0.233) or all-cause mortality (≥1: HR 1.08, 95% CI: 0.81–1.43; none: HR 0.66, 95% CI: 0.36–1.22; interaction P=0.154), regardless of exacerbation history. Aclidinium reduced the exacerbation rate vs placebo irrespective of exacerbation history (≥1: rate ratio [RR] 0.80, 95% CI: 0.68–0.94; none: RR 0.69, 95% CI: 0.54–0.89; interaction P=0.340) and improved FEV1 (interaction P=0.633). Conclusion: In patients with moderate-to-very severe COPD and increased cardiovascular risk, aclidinium did not increase risk of MACE or mortality and reduced exacerbation rate vs placebo, regardless of exacerbation history. Clinical Trial Registration: ClinicalTrials.gov Identifier: NCT01966107.
KW - Aclidinium
KW - COPD
KW - COPD exacerbation
KW - MACE
KW - Mortality
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U2 - 10.2147/COPD.S285068
DO - 10.2147/COPD.S285068
M3 - Article
C2 - 33776428
AN - SCOPUS:85103316035
SN - 1176-9106
VL - 16
SP - 689
EP - 699
JO - International Journal of COPD
JF - International Journal of COPD
ER -