Individual lifetime benefit from low-dose colchicine in patients with chronic coronary artery disease

Pascal M Burger; Jannick A N Dorresteijn; Aernoud T L Fiolet; Stefan Koudstaal; John W Eikelboom; Stefan M Nidorf; Peter L Thompson; Jan H Cornel; Charley A Budgeon; Iris C D Westendorp; Driek P W Beelen; Fabrice M A C Martens; Philippe Gabriel Steg; Folkert W Asselbergs; Maarten J Cramer; Martin Teraa; Deepak L Bhatt; Frank L J Visseren; Arend Mosterd; LoDoCo2 Trial Investigators; UCC-SMART Study Group; REACH Registry Investigators

doi:10.1093/eurjpc/zwad221

Individual lifetime benefit from low-dose colchicine in patients with chronic coronary artery disease

Eur J Prev Cardiol. 2023 Dec 21;30(18):1950-1962. doi: 10.1093/eurjpc/zwad221.

Authors

Pascal M Burger¹, Jannick A N Dorresteijn¹, Aernoud T L Fiolet^{2

3}, Stefan Koudstaal^{3

4}, John W Eikelboom⁵, Stefan M Nidorf^{6

7}, Peter L Thompson^{6

7}, Jan H Cornel^{3

8}, Charley A Budgeon⁹, Iris C D Westendorp¹⁰, Driek P W Beelen¹¹, Fabrice M A C Martens^{3

12}, Philippe Gabriel Steg¹³, Folkert W Asselbergs², Maarten J Cramer², Martin Teraa¹⁴, Deepak L Bhatt¹⁵, Frank L J Visseren¹, Arend Mosterd^{3

16}; LoDoCo2 Trial Investigators; UCC-SMART Study Group; REACH Registry Investigators

Collaborators

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, 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, F W Asselbergs, M J Cramer, M G van der Meer, H M Nathoe, G J de Borst, M L Bots, M H Emmelot-Vonk, P A de Jong, A T Lely, N P van der Kaaij, L J Kappelle, Y M Ruigrok, M C Verhaar, F L J Visseren, J A N Dorresteijn, D L Bhatt, P G Steg, E M Ohman, J Röther, P W F Wilson, M J Alberts, D L Bhatt, R D'Agostino, K A Eagle, S Goto, A T Hirsch, C S Liau, J L Mas, E M Ohman, J Röther, S C Smith, P G Steg, P W F Wilson

Affiliations

¹ Department of Vascular Medicine, University Medical Centre Utrecht, Utrecht, The Netherlands.
² Department of Cardiology, University Medical Centre Utrecht, Utrecht, The Netherlands.
³ Dutch Cardiovascular Research Network (WCN), Moreelsepark 1, 3511 EP Utrecht, The Netherlands.
⁴ Department of Cardiology, Green Heart Hospital, Gouda, The Netherlands.
⁵ Department of Medicine, McMaster University, Hamilton, Canada.
⁶ Department of Cardiology, GenesisCare Western Australia, Perth, Australia.
⁷ Heart Research Institute of Western Australia, Perth, Australia.
⁸ Department of Cardiology, Radboud University Medical Centre, Nijmegen, The Netherlands.
⁹ School of Population and Global Health, University of Western Australia, Perth, Australia.
¹⁰ Department of Cardiology, Red Cross Hospital, Beverwijk, The Netherlands.
¹¹ Department of Cardiology, IJsselland Hospital, Capelle aan den IJssel, The Netherlands.
¹² Department of Cardiology, Deventer Hospital, Deventer, The Netherlands.
¹³ Assistance Publique-Hôpitaux de Paris, Hôpital Bichat, Université de Paris, Paris, France.
¹⁴ Department of Vascular Surgery, University Medical Centre Utrecht, Utrecht, The Netherlands.
¹⁵ Mount Sinai Heart, Icahn School of Medicine at Mount Sinai Health System, New York, USA.
¹⁶ Department of Cardiology, Meander Medical Centre, Maatweg 3, 3813 TZ Amersfoort, The Netherlands.

PMID: 37409348
DOI: 10.1093/eurjpc/zwad221

Abstract

Aims: Low-dose colchicine reduces cardiovascular risk in patients with coronary artery disease (CAD), but absolute benefits may vary between individuals. This study aimed to assess the range of individual absolute benefits from low-dose colchicine according to patient risk profile.

Methods and results: The European Society of Cardiology (ESC) guideline-recommended SMART-REACH model was combined with the relative treatment effect of low-dose colchicine and applied to patients with CAD from the Low-Dose Colchicine 2 (LoDoCo2) trial and the Utrecht Cardiovascular Cohort-Second Manifestations of ARTerial disease (UCC-SMART) study (n = 10 830). Individual treatment benefits were expressed as 10-year absolute risk reductions (ARRs) for myocardial infarction, stroke, or cardiovascular death (MACE), and MACE-free life-years gained. Predictions were also performed for MACE plus coronary revascularization (MACE+), using a new lifetime model derived in the REduction of Atherothrombosis for Continued Health (REACH) registry. Colchicine was compared with other ESC guideline-recommended intensified (Step 2) prevention strategies, i.e. LDL cholesterol (LDL-c) reduction to 1.4 mmol/L and systolic blood pressure (SBP) reduction to 130 mmHg. The generalizability to other populations was assessed in patients with CAD from REACH North America and Western Europe (n = 25 812). The median 10-year ARR from low-dose colchicine was 4.6% [interquartile range (IQR) 3.6-6.0%] for MACE and 8.6% (IQR 7.6-9.8%) for MACE+. Lifetime benefit was 2.0 (IQR 1.6-2.5) MACE-free years, and 3.4 (IQR 2.6-4.2) MACE+-free life-years gained. For LDL-c and SBP reduction, respectively, the median 10-year ARR for MACE was 3.0% (IQR 1.5-5.1%) and 1.7% (IQR 0.0-5.7%), and the lifetime benefit was 1.2 (IQR 0.6-2.1) and 0.7 (IQR 0.0-2.3) MACE-free life-years gained. Similar results were obtained for MACE+ and in American and European patients from REACH.

Conclusion: The absolute benefits of low-dose colchicine vary between individual patients with chronic CAD. They may be expected to be of at least similar magnitude to those of intensified LDL-c and SBP reduction in a majority of patients already on conventional lipid-lowering and blood pressure-lowering therapy.

Keywords: Cardiovascular risk prediction; Colchicine; Coronary artery disease; ESC guidelines; Inflammation; Secondary prevention.

Plain language summary

The long-term benefits of treatment with low-dose colchicine were estimated for 36 642 individuals with coronary heart disease, and compared with those of lipid- and blood pressure–lowering therapy. On average, low-dose colchicine was estimated to lower the risk of cardiovascular disease in the next 10 years from 17.8 to 13.2% (a reduction of 4.6% points) and to afford 2.0 additional years of life without cardiovascular disease.Low-dose colchicine was estimated to be the most effective treatment in 49%, intensive blood pressure–lowering therapy in 28%, and intensive lipid-lowering therapy in 23% of patients.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Cholesterol, LDL
Colchicine / adverse effects
Coronary Artery Disease* / diagnosis
Coronary Artery Disease* / drug therapy
Humans
Hydroxymethylglutaryl-CoA Reductase Inhibitors* / therapeutic use
Myocardial Infarction* / drug therapy
Risk Factors

Substances

Hydroxymethylglutaryl-CoA Reductase Inhibitors
Cholesterol, LDL
Colchicine

Abstract

Plain language summary

Publication types

MeSH terms

Substances

Grants and funding