Individual lifetime benefit from low-dose colchicine in patients with chronic coronary artery disease
Authors: Burger Pascal M , Dorresteijn Jannick A N , Fiolet Aernoud T L , Koudstaal Stefan , Eikelboom John W , Nidorf Stefan M , Thompson Peter L , Cornel Jan H , Budgeon Charley A , Westendorp Iris C D , Beelen Driek P W , Martens Fabrice M A C , Steg Philippe Gabriel , Asselbergs Folkert W , Cramer Maarten J , Teraa Martin , Bhatt Deepak L , Visseren Frank L J , Mosterd Arend ,   for the LoDoCo2 Trial Investigators, Nidorf S M , Xu X F , Ireland M A , Latchem D , Whelan A , Hendriks R , Salkani P , Tan I W , Thompson A G , Morton A M , Hockings B E , Thompson P L , King B , Cornel J H , Bakker-Lohmeijer H , Mosterd A , Bunschoten P , The S H K , van der Kooi S , Lenderink T , Lardinois R G J L , Hoogslag P A M , de Vos A , Jerzewski A , Jansen S , Nierop P R , van der Knaap M , Swart H P , Kingma R , Schaap J , Blom L B , Kuijper A F M , Bayraktar-Verver E , van Hessen M W J , Engelen W C T C , van Eck J W M , van der Ven-Elzebroek N , van Hal J M C , Drost I M J , den Hartog F R , van Wijk D , van Beek E , van der Horst C , Bartels L , Hendriks M , de Nooijer C , Welten C , Ronner E , Dijkshoorn A , Prins F J , Rutten R N A , Beele D P W , Hendriks I , van der Sluis A , Badings E A , Westendorp I C D , Melein A , Römer Tj J , Bruines P , van de Wal R , Leenders - van Lieshout I , Hemels M E W , Meinen-Werner K , de Groot M R , Post G , Mulder M W C , Stuij S , van Nes E , Luyten P , Plomp J , Veldmeijer S V , Asselman M J , Scholtus P A ,   UCC-SMART Study Group, Asselbergs F W , Cramer M J , van der Meer M G , Nathoe H M , de Borst G J , Bots M L , Emmelot-Vonk M H , de Jong P A , Lely A T , van der Kaaij N P , Kappelle L J , Ruigrok Y M , Verhaar M C , Visseren F L J , Dorresteijn J A N ,   REACH Registry Investigators, Bhatt D L , Steg P G , Ohman E M , Röther J , Wilson P W F , Alberts M J , Bhatt D L , D’Agostino R , Eagle K A , Goto S , Hirsch A T , Liau C S , Mas J L , Ohman E M , Röther J , Smith S C , Steg P G , Wilson P W F 
Published: July 2023

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.