Abstract
Background
Reduction of inflammation with colchicine has emerged as a therapeutic option for
secondary prevention of cardiovascular disease (CVD) in patients with coronary artery
disease (CAD). Our objective was to consolidate evidence from randomized controlled
trials (RCTs) evaluating the efficacy and safety of low-dose colchicine for secondary
prevention of CVD among patients with CAD on standard medical therapy.
Methods
RCTs comparing the incidence of cardiovascular (CV) events between patients with clinically
manifest CAD randomized to colchicine vs placebo (or no colchicine) were included.
The primary composite efficacy endpoint included CV mortality, myocardial infarction
(MI), ischemic stroke, and urgent coronary revascularization. The DerSimonian and
Laird random-effects model was used to calculate pooled hazard ratios (HRs) and 95%
confidence intervals (CIs).
Results
Four RCTs, with a pooled sample size of 11,594 patients, were included (colchicine
n = 5774; placebo/no colchicine n = 5820). Included RCTs studied populations with
stable CAD (N = 2) and acute coronary syndrome (N = 2). Compared with placebo or no
colchicine, colchicine was associated with a statistically significant reduction in
the incidence of the primary composite endpoint (pooled HR, 0.68; 95% CI, 0.54-0.81;
I2 = 37.7%). The reduction in CV events among patients randomized to colchicine was
driven by statistically significant reductions in MIs, ischemic strokes, and urgent
coronary revascularizations (P < 0.05 for all) and was relatively consistent among subgroups. The incidence of safety
outcomes did not differ between groups (P > 0.05).
Conclusions
In secondary prevention of CV events, the addition of low-dose colchicine to standard
medical therapy reduces the incidence of major CV events—except CV mortality—when
compared with standard medical therapy alone.
Résumé
Contexte
L’emploi de la colchicine pour réduire l’inflammation s’est révélé être une option
thérapeutique dans le cadre de la prévention secondaire des maladies cardiovasculaires
(MCV) chez les patients atteints d’une coronaropathie. Notre objectif était de rassembler
les données probantes issues d’essais contrôlés avec répartition aléatoire évaluant
l’efficacité et l’innocuité de l’administration de colchicine à faible dose pour la
prévention secondaire des MCV chez les patients atteints d’une coronaropathie recevant
un traitement standard.
Méthodologie
Notre étude comprenait les essais contrôlés avec répartition aléatoire comparant l’incidence
des événements cardiovasculaires (CV) chez des patients atteints d’une coronaropathie
cliniquement observable et répartis aléatoirement pour recevoir de la colchicine ou
un placebo (ou un traitement sans colchicine). Le critère d’évaluation principal de
l’efficacité regroupait la mortalité d’origine CV, l’infarctus du myocarde (IM), l’accident
vasculaire cérébral (AVC) ischémique et la revascularisation coronaire d’urgence.
Le modèle à effets aléatoires DerSimonian-Laird a été utilisé pour calculer les rapports
des risques instantanés (RRI) groupés et les intervalles de confiance (IC) à 95 %.
Résultats
Quatre essais contrôlés avec répartition aléatoire, réunissant au total 11 594 patients,
ont été inclus (colchicine : n = 5774; placebo/traitement sans colchicine : n = 5820).
Deux de ces essais incluaient des patients atteints de coronaropathie stable (n =
2), et les deux autres, des patients présentant un syndrome coronarien aigu (n = 2).
Comparativement au placebo ou au traitement sans colchicine, la colchicine a entraîné
une réduction statistiquement significative de l’incidence des événements du critère
d’évaluation principal composé (RRI groupés : 0,68; IC à 95 % : de 0,54 à 0,81; I2 : 37,7 %). La réduction des événements CV chez les patients répartis aléatoirement
pour recevoir de la colchicine était due à des réductions statistiquement significatives
des IM, des AVC ischémiques et des revascularisations coronaires d’urgence (p < 0,05 dans tous les cas) et était relativement constante dans tous les sous-groupes.
L’incidence des problèmes d’innocuité était la même dans les deux groupes (p > 0,05).
Conclusions
Chez les patients en prévention secondaire des événements CV, l’ajout de colchicine
à faible dose au traitement standard réduit l’incidence des événements CV majeurs
– sauf la mortalité d’origine CV – comparativement au traitement standard seul.
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References
- Cardiovascular risk in post-myocardial infarction patients: nationwide real world data demonstrate the importance of a long-term perspective.Eur Heart J. 2015; 36: 1163-1170
- 2016 ACC/AHA guideline focused update on duration of dual antiplatelet therapy in patients with coronary artery disease: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines.J Am Coll Cardiol. 2016; 68: 1082-1115
- Global and regional patterns in cardiovascular mortality from 1990 to 2013.Circulation. 2015; 132: 1667-1678
- Inflammation, immunity, and infection in atherothrombosis: JACC Review Topic of the Week.J Am Coll Cardiol. 2018; 72: 2071-2081
- Inflammation, atherosclerosis, and coronary artery disease.N Engl J Med. 2005; 352: 1685-1695
- Antiinflammatory therapy with canakinumab for atherosclerotic disease.N Engl J Med. 2017; 377: 1119-1131
- Modulation of the interleukin-6 signalling pathway and incidence rates of atherosclerotic events and all-cause mortality: analyses from the Canakinumab Anti-Inflammatory Thrombosis Outcomes Study (CANTOS).Eur Heart J. 2018; 39: 3499-3507
- Relationship of C-reactive protein reduction to cardiovascular event reduction following treatment with canakinumab: a secondary analysis from the CANTOS randomised controlled trial.Lancet. 2018; 391: 319-328
- From CANTOS to CIRT to COLCOT to clinic: will all atherosclerosis patients soon be treated with combination lipid-lowering and inflammation-inhibiting agents?.Circulation. 2020; 141: 787-789
- Efficacy and safety of low-dose colchicine after myocardial infarction.N Engl J Med. 2019; 381: 2497-2505
- Low-dose colchicine for secondary prevention of cardiovascular disease.J Am Coll Cardiol. 2013; 61: 404-410
- Colchicine in patients with chronic coronary disease.N Engl J Med. 2020; 383: 1838-1847
- Colchicine in patients with acute coronary syndrome: the Australian COPS randomized clinical trial.Circulation. 2020; 142: 1890-1900
- Cost-effectiveness of low-dose colchicine after myocardial infarction in the Colchicine Cardiovascular Outcomes Trial (COLCOT).Eur Heart J Qual Care Clin Outcomes. 2020; ([Epub ahead of print])https://doi.org/10.1093/ehjqcco/qcaa045
- Colchicine: update on mechanisms of action and therapeutic uses.Semin Arthritis Rheum. 2015; 45: 341-350
- Colchicine alters the quantitative and qualitative display of selectins on endothelial cells and neutrophils.J Clin Invest. 1995; 96: 994-1002
- RoB 2: a revised tool for assessing risk of bias in randomised trials.BMJ. 2019; 366: I4898
- Measuring inconsistency in meta-analyses.BMJ. 2003; 327: 557-560
- Mechanism of action of colchicine in the treatment of gout.Clin Ther. 2014; 36: 1465-1479
- Effects of colchicine on risk of cardiovascular events and mortality among patients with gout: a cohort study using electronic medical records linked with Medicare claims.Ann Rheum Dis. 2016; 75: 1674-1679
- Colchicine use is associated with decreased prevalence of myocardial infarction in patients with gout.J Rheumatol. 2012; 39: 1458-1464
- Colchicine use and incident coronary artery disease in male patients with gout.Can J Cardiol. 2020; 36: 1722-1728
- Adverse events during oral colchicine use: a systematic review and meta-analysis of randomised controlled trials.Arthritis Res Ther. 2020; 22: 28
- Cardiovascular effects and safety of long-term colchicine treatment: Cochrane review and meta-analysis.Heart. 2016; 102: 590-596
Article Info
Publication History
Published online: October 16, 2020
Accepted:
October 14,
2020
Received:
September 26,
2020
Footnotes
See page 784 for disclosure information.
Identification
Copyright
© 2020 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.
