Colchicine in Patients With Chronic Coronary Disease in Relation to Prior Acute Coronary Syndrome

LoDoCo2 Trial Investigators

doi:10.1016/j.jacc.2021.06.037

Colchicine in Patients With Chronic Coronary Disease in Relation to Prior Acute Coronary Syndrome

LoDoCo2 Trial Investigators

Radboud University Medical Center
Department of Hematology, Northwest Clinics, Alkmaar, The Netherlands
University Medical Center Utrecht
Dutch Network for Cardiovascular Research, Netherlands
Meander Medical Center
McMaster University
Sir Charles Gairdner Hospital
GenesisCare Western Australia, Suite 3/140 Mounts Bay Rd, Perth WA 6000, Australia
University of Western Australia
The University of Western Australia
Department of Medical Oncology, Antonius Hospital Sneek, Postbus 20000, 8600BA, Sneek, The Netherlands
Pharmacy D&A Research, Sneek, the Netherlands
Jeroen Bosch Ziekenhuis
Department of Medical Microbiology, St Jansdal Hospital, Harderwijk, The Netherlands
Gelderland Valley Hospital
Amsterdam UMC - University of Amsterdam
Cardialysis BV, Netherlands
Radboud University Nijmegen
Department of Surgery, Northwest Clinics, Alkmaar, The Netherlands
Utrecht University
Dutch Network for Cardiovascular Research (WCN), Utrecht, The Netherlands
GenesisCare Western Australia, Perth, Western Australia, Australia
St Jansdal Hospital
Ziekenhuis Gelderse Vallei
University of Amsterdam
Cardialysis B.V.

Research output: Contribution to journal › Article › Academic › peer-review

Abstract

Background: Colchicine reduces risk of cardiovascular events in patients post–myocardial infarction and in patients with chronic coronary disease. It remains unclear whether this effect is related to the time of onset of treatment following an acute coronary syndrome (ACS). Objectives: This study investigates risk for major adverse cardiovascular events in relation to history and timing of prior ACS, to determine whether the benefits of colchicine are consistent independent of prior ACS status. Methods: The LoDoCo2 (Low-Dose Colchicine 2) trial randomly allocated patients with chronic coronary disease to colchicine 0.5 mg once daily or placebo. The rate of the composite of cardiovascular death, spontaneous myocardial infarction, ischemic stroke, or ischemia-driven coronary revascularization was compared between patients with no prior, recent (6-24 months), remote (2-7 years), or very remote (>7 years) ACS; interaction between ACS status and colchicine treatment effect was assessed. Results: In 5,522 randomized patients, risk of the primary endpoint was independent of prior ACS status. Colchicine consistently reduced the primary endpoint in patients with no prior ACS (incidence: 2.8 vs 3.4 events per 100 person-years; hazard ratio [HR]: 0.81; 95% confidence interval [CI]: 0.52-1.27), recent ACS (incidence: 2.4 vs 3.3 events per 100 person-years; HR: 0.75; 95% CI: 0.51-1.10), remote ACS (incidence: 1.8 vs 3.2 events per 100 person-years, HR: 0.55; 95% CI: 0.37-0.82), and very remote ACS (incidence: 3.0 vs 4.3 events per 100 person-years, HR: 0.70; 95% CI: 0.51-0.96) (P for interaction = 0.59). Conclusions: The benefits of colchicine are consistent irrespective of history and timing of prior ACS. (The LoDoCo2 Trial: Low Dose Colchicine for secondary prevention of cardiovascular disease [LoDoCo2] ACTRN12614000093684)

Original language	English
Pages (from-to)	859-866
Number of pages	8
Journal	Journal of the American College of Cardiology
Volume	78
Issue number	9
DOIs	https://doi.org/10.1016/j.jacc.2021.06.037
Publication status	Published - 31 Aug 2021

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Keywords

anti-inflammatory agents
atherosclerosis
cardiovascular inflammation
ischemic risk
myocardial infarction
secondary prevention

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10.1016/j.jacc.2021.06.037

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@article{ce9b9f3a385b4d13ba0707a0fc7ff05f,

title = "Colchicine in Patients With Chronic Coronary Disease in Relation to Prior Acute Coronary Syndrome",

abstract = "Background: Colchicine reduces risk of cardiovascular events in patients post–myocardial infarction and in patients with chronic coronary disease. It remains unclear whether this effect is related to the time of onset of treatment following an acute coronary syndrome (ACS). Objectives: This study investigates risk for major adverse cardiovascular events in relation to history and timing of prior ACS, to determine whether the benefits of colchicine are consistent independent of prior ACS status. Methods: The LoDoCo2 (Low-Dose Colchicine 2) trial randomly allocated patients with chronic coronary disease to colchicine 0.5 mg once daily or placebo. The rate of the composite of cardiovascular death, spontaneous myocardial infarction, ischemic stroke, or ischemia-driven coronary revascularization was compared between patients with no prior, recent (6-24 months), remote (2-7 years), or very remote (>7 years) ACS; interaction between ACS status and colchicine treatment effect was assessed. Results: In 5,522 randomized patients, risk of the primary endpoint was independent of prior ACS status. Colchicine consistently reduced the primary endpoint in patients with no prior ACS (incidence: 2.8 vs 3.4 events per 100 person-years; hazard ratio [HR]: 0.81; 95\% confidence interval [CI]: 0.52-1.27), recent ACS (incidence: 2.4 vs 3.3 events per 100 person-years; HR: 0.75; 95\% CI: 0.51-1.10), remote ACS (incidence: 1.8 vs 3.2 events per 100 person-years, HR: 0.55; 95\% CI: 0.37-0.82), and very remote ACS (incidence: 3.0 vs 4.3 events per 100 person-years, HR: 0.70; 95\% CI: 0.51-0.96) (P for interaction = 0.59). Conclusions: The benefits of colchicine are consistent irrespective of history and timing of prior ACS. (The LoDoCo2 Trial: Low Dose Colchicine for secondary prevention of cardiovascular disease [LoDoCo2] ACTRN12614000093684)",

keywords = "anti-inflammatory agents, atherosclerosis, cardiovascular inflammation, ischemic risk, myocardial infarction, secondary prevention",

author = "Opstal, \{Tjerk S. J.\} and Fiolet, \{Aernoud T. L.\} and \{van Broekhoven\}, Amber and Arend Mosterd and Eikelboom, \{John W.\} and Nidorf, \{Stefan M.\} and Thompson, \{Peter L.\} and Michiel Duyvendak and \{van Eck\}, \{J. W. Martijn\} and \{van Beek\}, \{Eug{\`e}ne A.\} and \{den Hartog\}, Frank and Budgeon, \{Charley A.\} and Bax, \{Willem A.\} and Tijssen, \{Jan G. P.\} and \{el Messaoudi\}, Saloua and Cornel, \{Jan H.\} and \{LoDoCo2 Trial Investigators\} and Nidorf, \{S. M.\} and Xu, \{X. F.\} and Ireland, \{M. A.\} and D. Latchem and A. Whelan and R. Hendriks and P. Salkani and Tan, \{I. W.\} and Thompson, \{A. G.\} and Morton, \{A. M.\} and Hockings, \{B. E.\} and Thompson, \{P. L.\} and B. King and Cornel, \{J. H.\} and H. Bakker-Lohmeijer and A. Mosterd and P. Bunschoten and The, \{S. H. K.\} and \{van der Kooi\}, S. and T. Lenderink and Lardinois, \{R. G. J. L.\} and Hoogslag, \{P. A. M.\} and \{de Vos\}, A. and A. Jerzewski and S. Jansen and Nierop, \{P. R.\} and \{van der Knaap\}, M. and Swart, \{H. P.\} and R. Kingma and J. Schaap and Blom, \{L. B.\} and Kuijper, \{A. F. M.\} and E. Bayraktar-Verver and \{van der Horst\}, C. and \{van Hessen\}, \{M. W. J.\} and Engelen, \{W. C. T. C.\} and \{van der Ven-Elzebroek\}, N. and \{van Hal\}, \{J. M. C.\} and Drost, \{I. M. J.\} and \{van Wijk\}, D. and Bartels, \{G. L.\} and M. Hendriks and \{de Nooijer\}, C. and C. Welten and E. Ronner and A. Dijkshoorn and Prins, \{F. J.\} and Rutten, \{R. N. A.\} and Beele, \{D. P. W.\} and I. Hendriks and \{van der Sluis\}, A. and Badings, \{E. A.\} and Westendorp, \{I. C. D.\} and A. Melein and Tj.J. R{\"o}mer and P. Bruines and \{van de Wal\}, R. and \{Leenders - van Lieshout\}, I. and Hemels, \{M. E. W.\} and K. Meinen-Werner and \{de Groot\}, \{M. R.\} and G. Post and Mulder, \{M. W. C.\} and S. Stuij and \{van Nes\}, E. and P. Luyten and J. Plomp and Veldmeijer, \{S. V.\} and Asselman, \{M. J.\} and Scholtus, \{P. A.\}",

note = "Funding Information: The authors thank all the patients for their participation in the trial; the trial investigators and coordinators at all the centers; and the trial monitors and staff from GenesisCare (including Penny Buczec, Denny Craig, Karen Doherty, Louise Ferguson, Louise Nidorf, and Karen Youl), the Heart and Vascular Research Institute of Sir Charles Gairdner Hospital (including Louise Ferguson), and the Dutch Network for Cardiovascular Research (including Marjelle van Leeuwen [project manager]; Ingrid Groenenberg and Glentino Rodriguez for data management; Erik Stroes, Max Silvis, and Tim de Vries for medical review; and Petra Bunschoten and Wendy Tousain for site monitoring). Funding Information: This trial was supported by the National Health Medical Research Council of Australia; a grant from the Sir Charles Gairdner Research Advisory Committee; the Withering Foundation (the Netherlands); the Netherlands Heart Foundation; the Netherlands Organization for Health Research and Development; and a consortium of Teva, Disphar, and Tiofarma in the Netherlands. The funders did not have any role in the design or conduct of the study; in the collection, analysis, or interpretation of the data; or in the preparation, review, or approval of the manuscript. Dr Mosterd has received grants from Novartis; and has received personal fees from Amarin, Amgen, Bristol Myers Squibb, Boehringer Ingelheim, Merck Sharp and Dohme, and Pfizer. Dr Eikelboom has received consulting/honoraria support from AstraZeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, Daiichi Sankyo, Eli Lilly, GlaxoSmithKline, Pfizer, Janssen, Sanofi, and Servier; and has received grants and/or in-kind support from AstraZeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, GlaxoSmithKline, Pfizer, Janssen, and Sanofi. Dr Thompson has received grants, travel support, and honoraria from Amarin, Amgen, AstraZeneca, Bristol Myers Squibb, Merck, and Pfizer. Dr Cornel has served on the advisory board for Amgen and AstraZeneca. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. Publisher Copyright: {\textcopyright} 2021 American College of Cardiology Foundation",

year = "2021",

month = aug,

day = "31",

doi = "10.1016/j.jacc.2021.06.037",

language = "English",

volume = "78",

pages = "859--866",

journal = "Journal of the American College of Cardiology",

issn = "0735-1097",

publisher = "Elsevier USA",

number = "9",

}

TY - JOUR

T1 - Colchicine in Patients With Chronic Coronary Disease in Relation to Prior Acute Coronary Syndrome

AU - Opstal, Tjerk S. J.

AU - Fiolet, Aernoud T. L.

AU - van Broekhoven, Amber

AU - Mosterd, Arend

AU - Eikelboom, John W.

AU - Nidorf, Stefan M.

AU - Thompson, Peter L.

AU - Duyvendak, Michiel

AU - van Eck, J. W. Martijn

AU - van Beek, Eugène A.

AU - den Hartog, Frank

AU - Budgeon, Charley A.

AU - Bax, Willem A.

AU - Tijssen, Jan G. P.

AU - el Messaoudi, Saloua

AU - Cornel, Jan H.

AU - LoDoCo2 Trial Investigators

AU - Nidorf, S. M.

AU - Xu, X. F.

AU - Ireland, M. A.

AU - Latchem, D.

AU - Whelan, A.

AU - Hendriks, R.

AU - Salkani, P.

AU - Tan, I. W.

AU - Thompson, A. G.

AU - Morton, A. M.

AU - Hockings, B. E.

AU - Thompson, P. L.

AU - King, B.

AU - Cornel, J. H.

AU - Bakker-Lohmeijer, H.

AU - Mosterd, A.

AU - Bunschoten, P.

AU - The, S. H. K.

AU - van der Kooi, S.

AU - Lenderink, T.

AU - Lardinois, R. G. J. L.

AU - Hoogslag, P. A. M.

AU - de Vos, A.

AU - Jerzewski, A.

AU - Jansen, S.

AU - Nierop, P. R.

AU - van der Knaap, M.

AU - Swart, H. P.

AU - Kingma, R.

AU - Schaap, J.

AU - Blom, L. B.

AU - Kuijper, A. F. M.

AU - Bayraktar-Verver, E.

AU - van der Horst, C.

AU - van Hessen, M. W. J.

AU - Engelen, W. C. T. C.

AU - van der Ven-Elzebroek, N.

AU - van Hal, J. M. C.

AU - Drost, I. M. J.

AU - van Wijk, D.

AU - Bartels, G. L.

AU - Hendriks, M.

AU - de Nooijer, C.

AU - Welten, C.

AU - Ronner, E.

AU - Dijkshoorn, A.

AU - Prins, F. J.

AU - Rutten, R. N. A.

AU - Beele, D. P. W.

AU - Hendriks, I.

AU - van der Sluis, A.

AU - Badings, E. A.

AU - Westendorp, I. C. D.

AU - Melein, A.

AU - Römer, Tj.J.

AU - Bruines, P.

AU - van de Wal, R.

AU - Leenders - van Lieshout, I.

AU - Hemels, M. E. W.

AU - Meinen-Werner, K.

AU - de Groot, M. R.

AU - Post, G.

AU - Mulder, M. W. C.

AU - Stuij, S.

AU - van Nes, E.

AU - Luyten, P.

AU - Plomp, J.

AU - Veldmeijer, S. V.

AU - Asselman, M. J.

AU - Scholtus, P. A.

N1 - Funding Information: The authors thank all the patients for their participation in the trial; the trial investigators and coordinators at all the centers; and the trial monitors and staff from GenesisCare (including Penny Buczec, Denny Craig, Karen Doherty, Louise Ferguson, Louise Nidorf, and Karen Youl), the Heart and Vascular Research Institute of Sir Charles Gairdner Hospital (including Louise Ferguson), and the Dutch Network for Cardiovascular Research (including Marjelle van Leeuwen [project manager]; Ingrid Groenenberg and Glentino Rodriguez for data management; Erik Stroes, Max Silvis, and Tim de Vries for medical review; and Petra Bunschoten and Wendy Tousain for site monitoring). Funding Information: This trial was supported by the National Health Medical Research Council of Australia; a grant from the Sir Charles Gairdner Research Advisory Committee; the Withering Foundation (the Netherlands); the Netherlands Heart Foundation; the Netherlands Organization for Health Research and Development; and a consortium of Teva, Disphar, and Tiofarma in the Netherlands. The funders did not have any role in the design or conduct of the study; in the collection, analysis, or interpretation of the data; or in the preparation, review, or approval of the manuscript. Dr Mosterd has received grants from Novartis; and has received personal fees from Amarin, Amgen, Bristol Myers Squibb, Boehringer Ingelheim, Merck Sharp and Dohme, and Pfizer. Dr Eikelboom has received consulting/honoraria support from AstraZeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, Daiichi Sankyo, Eli Lilly, GlaxoSmithKline, Pfizer, Janssen, Sanofi, and Servier; and has received grants and/or in-kind support from AstraZeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, GlaxoSmithKline, Pfizer, Janssen, and Sanofi. Dr Thompson has received grants, travel support, and honoraria from Amarin, Amgen, AstraZeneca, Bristol Myers Squibb, Merck, and Pfizer. Dr Cornel has served on the advisory board for Amgen and AstraZeneca. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. Publisher Copyright: © 2021 American College of Cardiology Foundation

PY - 2021/8/31

Y1 - 2021/8/31

N2 - Background: Colchicine reduces risk of cardiovascular events in patients post–myocardial infarction and in patients with chronic coronary disease. It remains unclear whether this effect is related to the time of onset of treatment following an acute coronary syndrome (ACS). Objectives: This study investigates risk for major adverse cardiovascular events in relation to history and timing of prior ACS, to determine whether the benefits of colchicine are consistent independent of prior ACS status. Methods: The LoDoCo2 (Low-Dose Colchicine 2) trial randomly allocated patients with chronic coronary disease to colchicine 0.5 mg once daily or placebo. The rate of the composite of cardiovascular death, spontaneous myocardial infarction, ischemic stroke, or ischemia-driven coronary revascularization was compared between patients with no prior, recent (6-24 months), remote (2-7 years), or very remote (>7 years) ACS; interaction between ACS status and colchicine treatment effect was assessed. Results: In 5,522 randomized patients, risk of the primary endpoint was independent of prior ACS status. Colchicine consistently reduced the primary endpoint in patients with no prior ACS (incidence: 2.8 vs 3.4 events per 100 person-years; hazard ratio [HR]: 0.81; 95% confidence interval [CI]: 0.52-1.27), recent ACS (incidence: 2.4 vs 3.3 events per 100 person-years; HR: 0.75; 95% CI: 0.51-1.10), remote ACS (incidence: 1.8 vs 3.2 events per 100 person-years, HR: 0.55; 95% CI: 0.37-0.82), and very remote ACS (incidence: 3.0 vs 4.3 events per 100 person-years, HR: 0.70; 95% CI: 0.51-0.96) (P for interaction = 0.59). Conclusions: The benefits of colchicine are consistent irrespective of history and timing of prior ACS. (The LoDoCo2 Trial: Low Dose Colchicine for secondary prevention of cardiovascular disease [LoDoCo2] ACTRN12614000093684)

AB - Background: Colchicine reduces risk of cardiovascular events in patients post–myocardial infarction and in patients with chronic coronary disease. It remains unclear whether this effect is related to the time of onset of treatment following an acute coronary syndrome (ACS). Objectives: This study investigates risk for major adverse cardiovascular events in relation to history and timing of prior ACS, to determine whether the benefits of colchicine are consistent independent of prior ACS status. Methods: The LoDoCo2 (Low-Dose Colchicine 2) trial randomly allocated patients with chronic coronary disease to colchicine 0.5 mg once daily or placebo. The rate of the composite of cardiovascular death, spontaneous myocardial infarction, ischemic stroke, or ischemia-driven coronary revascularization was compared between patients with no prior, recent (6-24 months), remote (2-7 years), or very remote (>7 years) ACS; interaction between ACS status and colchicine treatment effect was assessed. Results: In 5,522 randomized patients, risk of the primary endpoint was independent of prior ACS status. Colchicine consistently reduced the primary endpoint in patients with no prior ACS (incidence: 2.8 vs 3.4 events per 100 person-years; hazard ratio [HR]: 0.81; 95% confidence interval [CI]: 0.52-1.27), recent ACS (incidence: 2.4 vs 3.3 events per 100 person-years; HR: 0.75; 95% CI: 0.51-1.10), remote ACS (incidence: 1.8 vs 3.2 events per 100 person-years, HR: 0.55; 95% CI: 0.37-0.82), and very remote ACS (incidence: 3.0 vs 4.3 events per 100 person-years, HR: 0.70; 95% CI: 0.51-0.96) (P for interaction = 0.59). Conclusions: The benefits of colchicine are consistent irrespective of history and timing of prior ACS. (The LoDoCo2 Trial: Low Dose Colchicine for secondary prevention of cardiovascular disease [LoDoCo2] ACTRN12614000093684)

KW - anti-inflammatory agents

KW - atherosclerosis

KW - cardiovascular inflammation

KW - ischemic risk

KW - myocardial infarction

KW - secondary prevention

UR - https://www.scopus.com/pages/publications/85112566747

U2 - 10.1016/j.jacc.2021.06.037

DO - 10.1016/j.jacc.2021.06.037

M3 - Article

C2 - 34446156

SN - 0735-1097

VL - 78

SP - 859

EP - 866

JO - Journal of the American College of Cardiology

JF - Journal of the American College of Cardiology

IS - 9

ER -

Colchicine in Patients With Chronic Coronary Disease in Relation to Prior Acute Coronary Syndrome

Abstract

UN SDGs

Keywords

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