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

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.
Competing Interests: Conflict of interest: J.W.E. reported receiving grants from AstraZeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, GlaxoSmithKline, Pfizer, Janssen, and Sanofi-Aventis; and honoraria from AstraZeneca, Bayer, Boehringer Ingelheim, Bristol Myer Squibb, Daiichi Sankyo, Eli Lilly, GlaxoSmithKline, Merck, Pfizer, Janssen, Sanofi-Aventis, and Servier. P.L.T. reported receiving institutional research grants from the National Health Medical Research Council of Australia and Sir Charles Gairdner Research Advisory Committee; and the provision of colchicine and a matching placebo from Aspen Pharma Australia. J.H.C. reported receiving institutional research grants from the Withering Foundation Netherlands, The Netherlands Heart Foundation, The Netherlands Organization for Health Research and Development, and a consortium of Teva, Disphar, and Tiofarma; and consulting fees from Amgen and Sanofi. P.G.S. reported receiving research grants from Bristol Myers Squibb/Sanofi, Amarin, Bayer, and Servier; and consulting fees from Amarin, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squibb/Myokardia, Idorsia, Merck, Novartis, Novo Nordisk, Regeneron, PhaseBio, Pfizer, Sanofi, and Servier; and honoraria from AstraZeneca, Novartis, and Novo Nordisk; and support for attending meetings from AstraZeneca; and participating in advisory boards for Monash University, PHRI, Sanofi, and Servier. D.L.B. discloses the following relationships: Advisory Board: Angiowave, Bayer, Boehringer Ingelheim, Cardax, CellProthera, Cereno Scientific, Elsevier Practice Update Cardiology, High Enroll, Janssen, Level Ex, McKinsey, Medscape Cardiology, Merck, MyoKardia, NirvaMed, Novo Nordisk, PhaseBio, PLx Pharma, Regado Biosciences, and Stasys; Board of Directors: Angiowave (stock options), Boston VA Research Institute, Bristol Myers Squibb (stock), DRS. LINQ (stock options), High Enroll (stock), Society of Cardiovascular Patient Care, and TobeSoft; Chair: Inaugural chair, American Heart Association Quality Oversight Committee; Consultant: Broadview Ventures, Hims; Data Monitoring Committee: Acesion Pharma, Assistance Publique-Hôpitaux de Paris, Baim Institute for Clinical Research (formerly Harvard Clinical Research Institute, for the PORTICO trial, funded by St Jude Medical, now Abbott), Boston Scientific (Chair, PEITHO trial), Cleveland Clinic (including for the ExCEED trial, funded by Edwards), Contego Medical (Chair, PERFORMANCE 2), Duke Clinical Research Institute, Mayo Clinic, Mount Sinai School of Medicine (for the ENVISAGE trial, funded by Daiichi Sankyo; for the ABILITY-DM trial, funded by Concept Medical), Novartis, Population Health Research Institute, and Rutgers University (for the NIH-funded MINT Trial); Honoraria: American College of Cardiology (Senior Associate Editor, Clinical Trials and News, and ACC.org; Chair, ACC Accreditation Oversight Committee), Arnold and Porter law firm (work related to Sanofi/Bristol-Myers Squibb clopidogrel litigation), Baim Institute for Clinical Research (formerly Harvard Clinical Research Institute; RE-DUAL PCI clinical trial steering committee, funded by Boehringer Ingelheim; AEGIS-II executive committee, funded by CSL Behring), Belvoir Publications (Editor-in-Chief, Harvard Heart Letter), Canadian Medical and Surgical Knowledge Translation Research Group (clinical trial steering committees), CSL Behring (AHA lecture), Cowen and Company, Duke Clinical Research Institute (clinical trial steering committees, including for the PRONOUNCE trial, funded by Ferring Pharmaceuticals), HMP Global (Editor-in-Chief, Journal of Invasive Cardiology), Journal of the American College of Cardiology (Guest Editor, Associate Editor), K2P (Co-Chair, interdisciplinary curriculum), Level Ex, Medtelligence/ReachMD (CME steering committees), MJH Life Sciences, Oakstone CME (Course Director, Comprehensive Review of Interventional Cardiology), Piper Sandler, Population Health Research Institute (for the COMPASS operations committee, publications committee, steering committee, and US national co-leader, funded by Bayer), Slack Publications (Chief Medical Editor, Cardiology Today’s Intervention), Society of Cardiovascular Patient Care (Secretary/Treasurer), WebMD (CME steering committees), and Wiley (steering committee); Other: Clinical Cardiology (Deputy Editor), NCDR-ACTION Registry Steering Committee (Chair), and VA CART Research and Publications Committee (Chair); Patent: Sotagliflozin (named on a patent for sotagliflozin assigned to Brigham and Women's Hospital who assigned to Lexicon; neither I nor Brigham and Women's Hospital receive any income from this patent); Research Funding: Abbott, Acesion Pharma, Afimmune, Aker Biomarine, Alnylam, Amarin, Amgen, AstraZeneca, Bayer, Beren, Boehringer Ingelheim, Boston Scientific, Bristol Myers Squibb, Cardax, CellProthera, Cereno Scientific, Chiesi, CinCor, Cleerly, CSL Behring, Eisai, Ethicon, Faraday Pharmaceuticals, Ferring Pharmaceuticals, Forest Laboratories, Fractyl, Garmin, HLS Therapeutics, Idorsia, Ironwood, Ischemix, Janssen, Javelin, Lexicon, Lilly, Medtronic, Merck, Moderna, MyoKardia, NirvaMed, Novartis, Novo Nordisk, Otsuka, Owkin, Pfizer, PhaseBio, PLx Pharma, Recardio, Regeneron, Reid Hoffman Foundation, Roche, Sanofi, Stasys, Synaptic, The Medicines Company, Youngene, and 89Bio; Royalties: Elsevier (Editor, Braunwald’s Heart Disease); Site Co-Investigator: Abbott, Biotronik, Boston Scientific, CSI, Endotronix, St Jude Medical (now Abbott), Philips, SpectraWAVE, Svelte, and Vascular Solutions; Trustee: American College of Cardiology; Unfunded Research: FlowCo, and Takeda. A.M. reported institutional research grants from the Withering Foundation The Netherlands, The Netherlands Heart Foundation, The Netherlands Organization for Health Research and Development, Novartis, and a consortium of Teva, Disphar, and Tiofarma; A.M. will not accept personal fees from pharma. Other authors reported no disclosures.
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