TY - JOUR
T1 - Efficacy of Aclidinium Bromide According to Baseline Therapy
T2 - Post-Hoc Analysis of ASCENT-COPD Randomized Trial
AU - Wise, Robert A.
AU - Scirica, Benjamin M.
AU - Bhatt, Deepak L.
AU - Daoud, Sami Z.
AU - Chuecos, Ferran
AU - Garcia Gil, Esther
AU - Chapman, Kenneth R.
N1 - Funding Information:
Robert A. Wise reports personal fees from AstraZeneca, during the conduct of the study; personal fees from AbbVie, Anaptsys Bio, Circassia, Contrafect, Galderma, GSK, Kamada, Kinevant, Kiniksa, Merck, Novartis, Pneuma, Propeller Health, Pulmonx, Roche, Sunovion, and Verona; grants from Pearl Therapeutics; and grants and personal fees from AstraZeneca/MedImmune and Boehringer Ingelheim, outside the submitted work. Benjamin M. Scirica reports an institutional research grant to Brigham and Women’s Hospital from AstraZeneca, during the conduct of the study; consulting fees from AbbVie, Allergan, AstraZeneca, Boehringer Ingelheim, Eisai, Elsevier Practice Update Cardiology, Esperion, Hamni, Lexicon, Medtronic, Merck, and Novo Nordisk; equity in Health[at]Scale; grants from Eisai, Merck, Novartis, Novo Nordisk, and Pfizer, outside of the submitted work. Deepak L. Bhatt discloses the following relationships - Advisory Board: Cardax, CellProthera, Cereno Scientific, Elsevier Practice Update Cardiology, Janssen, Level Ex, Medscape Cardiology, MyoKardia, NirvaMed, Novo Nordisk, PhaseBio, PLx Pharma, and Regado Biosciences; Board of Directors: Boston VA Research Institute, Society of Cardiovascular Patient Care, TobeSoft; Chair: American Heart Association Quality Oversight Committee; Data Monitoring Committees: Baim Institute for Clinical Research (formerly Harvard Clinical Research Institute, for the PORTICO trial, funded by St. Jude Medical, now Abbott), Cleveland Clinic (including for the ExCEED trial, funded by Edwards), Contego Medical (Chair, PERFORMANCE 2), Duke Clinical Research Institute, Mayo Clinic, Mount Sinai School of Medicine (for the ENVISAGE trial, funded by Daiichi Sankyo), and Population Health Research Institute; Honoraria: American College of Cardiology (Senior Associate Editor, Clinical Trials and News, ACC.org; Chair, ACC Accreditation Committee), Baim Institute for Clinical Research (formerly Harvard Clinical Research Institute; RE-DUAL PCI clinical trial steering committee funded by Boehringer Ingelheim; AEGIS-II executive committee funded by CSL Behring), Belvoir Publications (Editor-in-Chief, Harvard Heart Letter), Canadian Medical and Surgical Knowledge Translation Research Group (clinical trial steering committees), Duke Clinical Research Institute (clinical trial steering committees, including for the PRONOUNCE trial, funded by Ferring Pharmaceuticals), HMP Global (Editor-in-Chief, Journal of Invasive Cardiology), Journal of the American College of Cardiology (Guest Editor; Associate Editor), K2P (Co-Chair, interdisciplinary curriculum), Level Ex, Medtelligence/ReachMD (CME steering committees), MJH Life Sciences, Population Health Research Institute (for the COMPASS operations committee, publications committee, steering committee, and USA national co-leader, funded by Bayer), Slack Publications (Chief Medical Editor, Cardiology Today’s Intervention), Society of Cardiovascular Patient Care (Secretary/Treasurer), and WebMD (CME steering committees); Other: Clinical Cardiology (Deputy Editor), NCDR-ACTION Registry Steering Committee (Chair), and VA CART Research and Publications Committee (Chair); Research Funding: Abbott, Afimmune, Amarin, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Cardax, CellProthera, Cereno Scientific, Chiesi, CSL Behring, Eisai, Ethicon, Ferring Pharmaceuticals, Forest Laboratories, Fractyl, Garmin, HLS Therapeutics, Idorsia, Ironwood, Ischemix, Janssen, Lexicon, Lilly, Medtronic, MyoKardia, NirvaMed, Novartis, Novo Nordisk, Owkin, Pfizer, PhaseBio, PLx Pharma, Regeneron, Roche, Sanofi, Synaptic, The Medicines Company, and 89Bio; Royalties: Elsevier (Editor, Cardiovascular Intervention: A Companion to Braunwald’s Heart Disease); Site Co-Investigator: Abbott, Biotronik, Boston Scientific, CSI, St. Jude Medical (now Abbott), and Svelte; Trustee: American College of Cardiology; Unfunded Research: FlowCo, Merck, and Takeda. Sami Z. Daoud is an employee and shareholder of AstraZeneca. Esther Garcia Gil was an employee and shareholder of AstraZeneca at the time of the study and is now an employee of Almirall S.A., Barcelona, Spain. Ferran Chuecos is an employee of AstraZeneca. Kenneth R. Chapman reports grants from Amgen, Baxter, GSK, and Shire, personal fees from CIHR-GSK Research Chair in Respiratory Healthcare Delivery (UHN) and Merck; grants and personal fees from AstraZeneca, Boehringer Ingelheim, CSL Behring, Genentech, Grifols, Kamada, Novartis, Roche, and Sanofi, during the conduct of the study.
Funding Information:
The authors thank Dan Lythgoe, of Phastar, who provided statistical consultation. Medical writing support was provided by Richard Knight, PhD, and Sarah Hoyle, PhD, of CMC Connect, McCann Health Medical Communications, and was funded by AstraZeneca, in accordance with Good Publication Practice (GPP3) guidelines.
Funding Information:
The ASCENT-COPD study was initially funded by Forest Laboratories and later funded by AstraZeneca and Circassia. AstraZeneca funded the journal’s Rapid Service and Open Access Fees.
Publisher Copyright:
© 2021, The Author(s).
PY - 2021/10
Y1 - 2021/10
N2 - Introduction: Long-acting muscarinic antagonists (LAMAs), long-acting β2-agonists (LABAs), inhaled corticosteroids (ICS), and their combinations, are recommended for the treatment of chronic obstructive pulmonary disease (COPD). This study aimed to determine whether the safety and efficacy of aclidinium bromide differs by baseline maintenance LABA and ICS therapies. Methods: ASCENT-COPD was a phase 4, multicenter, double-blind, randomized, 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 400 μg or placebo twice daily, via a multidose dry-powder inhaler for up to 3 years. Outcomes included time to first major adverse cardiovascular events (MACE), all-cause mortality, change from baseline in trough forced expiratory volume in 1 s (FEV1), and COPD assessment test (CAT) total score over 3 years, and annual moderate-to-severe COPD exacerbation rate in patients receiving aclidinium or placebo with maintenance LABA monotherapy, ICS monotherapy, LABA + ICS (fixed/free), or no maintenance therapy (neither LABA nor ICS) at baseline. Results: A total of 3589 patients were included (LABA, n = 227; ICS, n = 290; LABA + ICS, n = 2058; no maintenance, n = 1130). Aclidinium did not increase the risk of MACE or all-cause mortality versus placebo, regardless of baseline maintenance treatment. Reductions in moderate-to-severe exacerbation rates were observed with aclidinium versus placebo in all subgroups [LABA 43% (P = 0.046); ICS 25% (P = 0.202); LABA + ICS 22% (P = 0.003); no maintenance 18% (P = 0.130)]. Aclidinium improved morning trough FEV1 irrespective of baseline therapy and CAT total scores, except for LABA and ICS subgroups, versus placebo at several time points. Conclusion: In patients with moderate-to-severe COPD and CV risk factors, the addition of aclidinium to maintenance therapy with LABA or LABA + ICS provided further benefit. Trial Registration: ClinicalTrials.gov identifier NCT01966107.
AB - Introduction: Long-acting muscarinic antagonists (LAMAs), long-acting β2-agonists (LABAs), inhaled corticosteroids (ICS), and their combinations, are recommended for the treatment of chronic obstructive pulmonary disease (COPD). This study aimed to determine whether the safety and efficacy of aclidinium bromide differs by baseline maintenance LABA and ICS therapies. Methods: ASCENT-COPD was a phase 4, multicenter, double-blind, randomized, 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 400 μg or placebo twice daily, via a multidose dry-powder inhaler for up to 3 years. Outcomes included time to first major adverse cardiovascular events (MACE), all-cause mortality, change from baseline in trough forced expiratory volume in 1 s (FEV1), and COPD assessment test (CAT) total score over 3 years, and annual moderate-to-severe COPD exacerbation rate in patients receiving aclidinium or placebo with maintenance LABA monotherapy, ICS monotherapy, LABA + ICS (fixed/free), or no maintenance therapy (neither LABA nor ICS) at baseline. Results: A total of 3589 patients were included (LABA, n = 227; ICS, n = 290; LABA + ICS, n = 2058; no maintenance, n = 1130). Aclidinium did not increase the risk of MACE or all-cause mortality versus placebo, regardless of baseline maintenance treatment. Reductions in moderate-to-severe exacerbation rates were observed with aclidinium versus placebo in all subgroups [LABA 43% (P = 0.046); ICS 25% (P = 0.202); LABA + ICS 22% (P = 0.003); no maintenance 18% (P = 0.130)]. Aclidinium improved morning trough FEV1 irrespective of baseline therapy and CAT total scores, except for LABA and ICS subgroups, versus placebo at several time points. Conclusion: In patients with moderate-to-severe COPD and CV risk factors, the addition of aclidinium to maintenance therapy with LABA or LABA + ICS provided further benefit. Trial Registration: ClinicalTrials.gov identifier NCT01966107.
KW - Aclidinium bromide
KW - Chronic obstructive pulmonary disease
KW - Muscarinic antagonists
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U2 - 10.1007/s12325-021-01878-5
DO - 10.1007/s12325-021-01878-5
M3 - Article
C2 - 34528220
AN - SCOPUS:85114918476
SN - 0741-238X
VL - 38
SP - 5381
EP - 5397
JO - Advances in Therapy
JF - Advances in Therapy
IS - 10
ER -