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

Tjerk S J Opstal; Aernoud T L Fiolet; Amber van Broekhoven; Arend Mosterd; John W Eikelboom; Stefan M Nidorf; Peter L Thompson; Michiel Duyvendak; J W Martijn van Eck; Eugène A van Beek; Frank den Hartog; Charley A Budgeon; Willem A Bax; Jan G P Tijssen; Saloua El Messaoudi; Jan H Cornel; 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

J Am Coll Cardiol. 2021 Aug 31;78(9):859-866. doi: 10.1016/j.jacc.2021.06.037.

Authors

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

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.

Publication types

Randomized Controlled Trial
Research Support, Non-U.S. Gov't

MeSH terms

Acute Coronary Syndrome* / complications
Acute Coronary Syndrome* / diagnosis
Acute Coronary Syndrome* / drug therapy
Colchicine* / administration & dosage
Colchicine* / adverse effects
Dose-Response Relationship, Drug
Double-Blind Method
Drug Monitoring
Female
Gout Suppressants / administration & dosage
Gout Suppressants / adverse effects
Humans
Incidence
Male
Middle Aged
Myocardial Infarction / diagnosis
Myocardial Infarction / etiology
Outcome Assessment, Health Care
Risk Assessment
Secondary Prevention / methods
Stroke / diagnosis
Stroke / etiology
Time-to-Treatment

Substances

Gout Suppressants
Colchicine

Associated data

ANZCTR/ACTRN12614000093684