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Canadian Journal of Cardiology

Colchicine for Secondary Prevention of Cardiovascular Disease: A Systematic Review and Meta-analysis of Randomized Controlled Trials

Published:October 16, 2020DOI:https://doi.org/10.1016/j.cjca.2020.10.006

      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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