Randomized Controlled Trial

. 2021 Aug 31;78(9):859-866.

doi: 10.1016/j.jacc.2021.06.037.

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

Tjerk S J Opstal¹, Aernoud T L Fiolet², Amber van Broekhoven³, Arend Mosterd⁴, John W Eikelboom⁵, Stefan M Nidorf⁶, Peter L Thompson⁷, Michiel Duyvendak⁸, J W Martijn van Eck⁹, Eugène A van Beek¹⁰, Frank den Hartog¹¹, Charley A Budgeon¹², Willem A Bax¹³, Jan G P Tijssen¹⁴, Saloua El Messaoudi³, Jan H Cornel¹⁵; LoDoCo2 Trial Investigators

Collaborators, Affiliations

Collaborators

LoDoCo2 Trial Investigators:
S M Nidorf, X F Xu, M A Ireland, D Latchem, A Whelan, R Hendriks, P Salkani, I W Tan, A G Thompson, A M Morton, B E Hockings, P L Thompson, B King, J H Cornel, H Bakker-Lohmeijer, A Mosterd, P Bunschoten, S H K The, S van der Kooi, T Lenderink, R G J L Lardinois, P A M Hoogslag, A de Vos, A Jerzewski, S Jansen, P R Nierop, M van der Knaap, H P Swart, R Kingma, J Schaap, L B Blom, A F M Kuijper, E Bayraktar-Verver, M W J van Hessen, W C T C Engelen, J W M van Eck, N van der Ven-Elzebroek, J M C van Hal, I M J Drost, F R den Hartog, D van Wijk, E van Beek, C van der Horst, G L Bartels, M Hendriks, C de Nooijer, C Welten, E Ronner, A Dijkshoorn, F J Prins, R N A Rutten, D P W Beele, I Hendriks, A van der Sluis, E A Badings, I C D Westendorp, A Melein, Tj J Römer, P Bruines, R van de Wal, I Leenders-van Lieshout, M E W Hemels, K Meinen-Werner, M R de Groot, G Post, M W C Mulder, S Stuij, E van Nes, P Luyten, J Plomp, S V Veldmeijer, M J Asselman, P A Scholtus

Affiliations

¹ Department of Cardiology, Radboud University Medical Center, Nijmegen, the Netherlands; Department of Cardiology, Northwest Clinics, Alkmaar, the Netherlands. Electronic address: tjerk.opstal@radboudumc.nl.
² Department of Cardiology, University Medical Center Utrecht, Utrecht, the Netherlands; Dutch Network for Cardiovascular Research, Utrecht, the Netherlands.
³ Department of Cardiology, Radboud University Medical Center, Nijmegen, the Netherlands.
⁴ Dutch Network for Cardiovascular Research, Utrecht, the Netherlands; Department of Cardiology, Meander Medical Center, Amersfoort, the Netherlands.
⁵ Department of Medicine, McMaster University, Hamilton, Ontario, Canada.
⁶ Heart and Vascular Research Institute of Western Australia, Sir Charles Gairdner Hospital, Perth, Western Australia, Australia; GenesisCare Western Australia, Perth, Western Australia, Australia.
⁷ Heart and Vascular Research Institute of Western Australia, Sir Charles Gairdner Hospital, Perth, Western Australia, Australia; Harry Perkins Institute of Medical Research, Perth, Western Australia, Australia; University of Western Australia, Perth, Western Australia, Australia.
⁸ Department of Clinical Pharmacy, Antonius Hospital Sneek, Sneek, the Netherlands; Pharmacy D&A Research, Sneek, the Netherlands.
⁹ Department of Cardiology, Jeroen Bosch Hospital, 's-Hertogenbosch, the Netherlands.
¹⁰ Department of Cardiology, St Jansdal Hospital, Harderwijk, the Netherlands.
¹¹ Department of Cardiology, Gelderse Vallei Hospital, Ede, the Netherlands.
¹² University of Western Australia, Perth, Western Australia, Australia.
¹³ Department of Internal Medicine, Northwest Clinics, Alkmaar, the Netherlands.
¹⁴ Department of Cardiology, Amsterdam University Medical Center, Amsterdam, the Netherlands; Cardialysis BV, Rotterdam, the Netherlands.
¹⁵ Department of Cardiology, Radboud University Medical Center, Nijmegen, the Netherlands; Department of Cardiology, Northwest Clinics, Alkmaar, the Netherlands; Dutch Network for Cardiovascular Research, Utrecht, the Netherlands.

PMID: 34446156
DOI: 10.1016/j.jacc.2021.06.037

Free article

Randomized Controlled Trial

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

Tjerk S J Opstal et al. J Am Coll Cardiol. 2021.

Free article

. 2021 Aug 31;78(9):859-866.

doi: 10.1016/j.jacc.2021.06.037.

Authors

Collaborators

LoDoCo2 Trial Investigators:
S M Nidorf, X F Xu, M A Ireland, D Latchem, A Whelan, R Hendriks, P Salkani, I W Tan, A G Thompson, A M Morton, B E Hockings, P L Thompson, B King, J H Cornel, H Bakker-Lohmeijer, A Mosterd, P Bunschoten, S H K The, S van der Kooi, T Lenderink, R G J L Lardinois, P A M Hoogslag, A de Vos, A Jerzewski, S Jansen, P R Nierop, M van der Knaap, H P Swart, R Kingma, J Schaap, L B Blom, A F M Kuijper, E Bayraktar-Verver, M W J van Hessen, W C T C Engelen, J W M van Eck, N van der Ven-Elzebroek, J M C van Hal, I M J Drost, F R den Hartog, D van Wijk, E van Beek, C van der Horst, G L Bartels, M Hendriks, C de Nooijer, C Welten, E Ronner, A Dijkshoorn, F J Prins, R N A Rutten, D P W Beele, I Hendriks, A van der Sluis, E A Badings, I C D Westendorp, A Melein, Tj J Römer, P Bruines, R van de Wal, I Leenders-van Lieshout, M E W Hemels, K Meinen-Werner, M R de Groot, G Post, M W C Mulder, S Stuij, E van Nes, P Luyten, J Plomp, S V Veldmeijer, M J Asselman, P A Scholtus

Affiliations

¹ Department of Cardiology, Radboud University Medical Center, Nijmegen, the Netherlands; Department of Cardiology, Northwest Clinics, Alkmaar, the Netherlands. Electronic address: tjerk.opstal@radboudumc.nl.
² Department of Cardiology, University Medical Center Utrecht, Utrecht, the Netherlands; Dutch Network for Cardiovascular Research, Utrecht, the Netherlands.
³ Department of Cardiology, Radboud University Medical Center, Nijmegen, the Netherlands.
⁴ Dutch Network for Cardiovascular Research, Utrecht, the Netherlands; Department of Cardiology, Meander Medical Center, Amersfoort, the Netherlands.
⁵ Department of Medicine, McMaster University, Hamilton, Ontario, Canada.
⁶ Heart and Vascular Research Institute of Western Australia, Sir Charles Gairdner Hospital, Perth, Western Australia, Australia; GenesisCare Western Australia, Perth, Western Australia, Australia.
⁷ Heart and Vascular Research Institute of Western Australia, Sir Charles Gairdner Hospital, Perth, Western Australia, Australia; Harry Perkins Institute of Medical Research, Perth, Western Australia, Australia; University of Western Australia, Perth, Western Australia, Australia.
⁸ Department of Clinical Pharmacy, Antonius Hospital Sneek, Sneek, the Netherlands; Pharmacy D&A Research, Sneek, the Netherlands.
⁹ Department of Cardiology, Jeroen Bosch Hospital, 's-Hertogenbosch, the Netherlands.
¹⁰ Department of Cardiology, St Jansdal Hospital, Harderwijk, the Netherlands.
¹¹ Department of Cardiology, Gelderse Vallei Hospital, Ede, the Netherlands.
¹² University of Western Australia, Perth, Western Australia, Australia.
¹³ Department of Internal Medicine, Northwest Clinics, Alkmaar, the Netherlands.
¹⁴ Department of Cardiology, Amsterdam University Medical Center, Amsterdam, the Netherlands; Cardialysis BV, Rotterdam, the Netherlands.
¹⁵ Department of Cardiology, Radboud University Medical Center, Nijmegen, the Netherlands; Department of Cardiology, Northwest Clinics, Alkmaar, the Netherlands; Dutch Network for Cardiovascular Research, Utrecht, the Netherlands.

PMID: 34446156
DOI: 10.1016/j.jacc.2021.06.037

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.

PubMed Disclaimer

Conflict of interest statement

Funding Support and Author Disclosures 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.

Comment in

Low-Dose Colchicine for the Management of Coronary Artery Disease.
Tardif JC, Marquis-Gravel G. Tardif JC, et al. J Am Coll Cardiol. 2021 Aug 31;78(9):867-869. doi: 10.1016/j.jacc.2021.07.002. J Am Coll Cardiol. 2021. PMID: 34446157 No abstract available.

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ANZCTR/ACTRN12614000093684

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

Collaborators

Affiliations

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

Authors

Collaborators

Affiliations

Abstract

Conflict of interest statement

Comment in

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Associated data

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