Advertisement
Heart, Lung and Circulation

Colchicine for Secondary Prevention of Coronary Artery Disease: A Meta-Analysis of Randomised Controlled Trials

Published:January 12, 2022DOI:https://doi.org/10.1016/j.hlc.2021.09.017

      Background

      Colchicine has become prominent as an anti-inflammatory therapy for secondary cardiovascular prevention in patients with coronary artery disease (CAD). This meta-analysis was performed to evaluate the efficacy and safety of colchicine in patients with CAD.

      Methods

      Randomised controlled trials (RCTs) that compare major adverse cardiovascular events (MACEs) between patients with CAD randomised to colchicine versus placebo (or no colchicine) were included. Random effect risk ratios (RRs) were calculated for clinical outcomes.

      Results

      A total of 12,071 patients in seven RCTs were included in the meta-analysis. Compared with placebo or no colchicine, colchicine was associated with a significantly lower incidence of MACEs (RR 0.64, 95% CI 0.51–0.80, p<0.01). The reduction in MACEs in the colchicine group was driven by statistically significant reductions in the incidence of myocardial ischaemia (RR 0.74, 95% CI 0.58–0.95, p=0.02), coronary revascularisation (RR 0.61, 95% CI 0.42–0.89, p=0.01), and stroke (RR 0.48, 95% CI 0.28–0.83, p=0.01). However, there was no statistically significant difference for cardiovascular death (RR 0.82, 95% CI 0.55–1.22, p=0.33). All-cause and non-cardiovascular mortality, gastrointestinal events, infection, and cancer were not significantly different between the colchicine and control groups.

      Conclusions

      Colchicine is a reasonably efficacious and safe drug that could be successfully utilised for the secondary prevention of CAD.

      Keywords

      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to Heart, Lung and Circulation
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Levine G.N.
        • Bates E.R.
        • Bittl J.A.
        • Brindis R.G.
        • Fihn S.D.
        • Fleisher L.A.
        • et al.
        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
        • Zhou M.
        • Wang H.
        • Zeng X.
        • Yin P.
        • Zhu J.
        • Chen W.
        • et al.
        Mortality, morbidity, and risk factors in China and its provinces, 1990-2017: a systematic analysis for the Global Burden of Disease Study 2017.
        Lancet. 2019; 394: 1145-1158
        • Libby P.
        • Loscalzo J.
        • Ridker P.M.
        • Farkouh M.E.
        • Hsue P.Y.
        • Fuster V.
        • et al.
        Inflammation, immunity, and infection in atherothrombosis: JACC review topic of the week.
        J Am Coll Cardiol. 2018; 72: 2071-2081
        • Vergallo R.
        • Crea F.
        Atherosclerotic plaque healing.
        N Engl J Med. 2020; 383: 846-857
        • Ravelli R.B.
        • Gigant B.
        • Curmi P.A.
        • Jourdain I.
        • Lachkar S.
        • Sobel A.
        • et al.
        Insight into tubulin regulation from a complex with colchicine and a stathmin-like domain.
        Nature. 2004; 428: 198-202
        • Dalbeth N.
        • Lauterio T.J.
        • Wolfe H.R.
        Mechanism of action of colchicine in the treatment of gout.
        Clin Ther. 2014; 36: 1465-1479
        • El Hasbani G.
        • Jawad A.
        • Uthman I.
        Colchicine: An ancient drug with multiple benefits.
        Curr Pharm Des. 2021; 27: 2917-2924
        • Tardif J.C.
        • Kouz S.
        • Waters D.D.
        • Bertrand O.F.
        • Diaz R.
        • Maggioni A.P.
        • et al.
        Efficacy and safety of low-dose colchicine after myocardial infarction.
        N Engl J Med. 2019; 381: 2497-2505
        • Shah B.
        • Pillinger M.
        • Zhong H.
        • Cronstein B.
        • Xia Y.
        • Lorin J.D.
        • et al.
        Effects of acute colchicine administration prior to percutaneous coronary intervention: COLCHICINE-PCI randomized trial.
        Circ Cardiovasc Interv. 2020; 13: e008717
        • Nidorf S.M.
        • Fiolet A.T.L.
        • Mosterd A.
        • Eikelboom J.W.
        • Schut A.
        • Opstal T.S.J.
        • et al.
        Colchicine in patients with chronic coronary disease.
        N Engl J Med. 2020; 383: 1838-1847
        • Moher D.
        • Liberati A.
        • Tetzlaff J.
        • Altman D.G.
        • Group P.
        Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement.
        J Clin Epidemiol. 2009; 62: 1006-1012
        • Cumpston M.
        • Li T.
        • Page M.J.
        • Chandler J.
        • Welch V.A.
        • Higgins J.P.
        • et al.
        Updated guidance for trusted systematic reviews: a new edition of the Cochrane Handbook for Systematic Reviews of Interventions.
        Cochrane Database Syst Rev. 2019; 10: ED000142
        • Nidorf S.M.
        • Eikelboom J.W.
        • Budgeon C.A.
        • Thompson P.L.
        Low-dose colchicine for secondary prevention of cardiovascular disease.
        J Am Coll Cardiol. 2013; 61: 404-410
        • Tong D.C.
        • Quinn S.
        • Nasis A.
        • Hiew C.
        • Roberts-Thomson P.
        • Adams H.
        • et al.
        Colchicine in patients with acute coronary syndrome: The Australian COPS randomized clinical trial.
        Circulation. 2020; 142: 1890-1900
        • Hennessy T.
        • Soh L.
        • Bowman M.
        • Kurup R.
        • Schultz C.
        • Patel S.
        • et al.
        The Low Dose Colchicine after Myocardial Infarction (LoDoCo-MI) study: A pilot randomized placebo controlled trial of colchicine following acute myocardial infarction.
        Am Heart J. 2019; 215: 62-69
        • Deftereos S.
        • Giannopoulos G.
        • Raisakis K.
        • Kossyvakis C.
        • Kaoukis A.
        • Panagopoulou V.
        • et al.
        Colchicine treatment for the prevention of bare-metal stent restenosis in diabetic patients.
        J Am Coll Cardiol. 2013; 61: 1679-1685
        • Akodad M.
        • Lattuca B.
        • Nagot N.
        • Georgescu V.
        • Buisson M.
        • Cristol J.P.
        • et al.
        COLIN trial: value of colchicine in the treatment of patients with acute myocardial infarction and inflammatory response.
        Arch Cardiovasc Dis. 2017; 110: 395-402
        • Samuel M.
        • Tardif J.C.
        • Bouabdallaoui N.
        • Khairy P.
        • Dube M.P.
        • Blondeau L.
        • et al.
        Colchicine for secondary prevention of cardiovascular disease: a systematic review and meta-analysis of randomized controlled trials.
        Can J Cardiol. 2020; 37: 776-785
        • Xia M.
        • Yang X.
        • Qian C.
        Meta-analysis evaluating the utility of colchicine in secondary prevention of coronary artery disease.
        Am J Cardiol. 2021; 140: 33-38
        • Imazio M.
        • Belli R.
        • Brucato A.
        • Cemin R.
        • Ferrua S.
        • Beqaraj F.
        • et al.
        Efficacy and safety of colchicine for treatment of multiple recurrences of pericarditis (CORP-2): a multicentre, double-blind, placebo-controlled, randomised trial.
        Lancet. 2014; 383: 2232-2237
        • Stewart S.
        • Yang K.C.K.
        • Atkins K.
        • Dalbeth N.
        • Robinson P.C.
        Adverse events during oral colchicine use: a systematic review and meta-analysis of randomised controlled trials.
        Arthritis Res Ther. 2020; 22: 28
        • Kasikara C.
        • Doran A.C.
        • Cai B.
        • Tabas I.
        The role of non-resolving inflammation in atherosclerosis.
        J Clin Invest. 2018; 128: 2713-2723
        • Ridker P.M.
        • Everett B.M.
        • Thuren T.
        • MacFadyen J.G.
        • Chang W.H.
        • Ballantyne C.
        • et al.
        Antiinflammatory therapy with canakinumab for atherosclerotic disease.
        N Engl J Med. 2017; 377: 1119-1131
        • Ridker P.M.
        • Everett B.M.
        • Pradhan A.
        • MacFadyen J.G.
        • Solomon D.H.
        • Zaharris E.
        • et al.
        Low-dose methotrexate for the prevention of atherosclerotic events.
        N Engl J Med. 2019; 380: 752-762
        • Leung Y.Y.
        • Yao Hui L.L.
        • Kraus V.B.
        Colchicine--Update on mechanisms of action and therapeutic uses.
        Semin Arthritis Rheum. 2015; 45: 341-350
        • Cimmino G.
        • Tarallo R.
        • Conte S.
        • Morello A.
        • Pellegrino G.
        • Loffredo F.S.
        • et al.
        Colchicine reduces platelet aggregation by modulating cytoskeleton rearrangement via inhibition of cofilin and LIM domain kinase 1.
        Vascul Pharmacol. 2018; 111: 62-70
        • Martinez G.J.
        • Robertson S.
        • Barraclough J.
        • Xia Q.
        • Mallat Z.
        • Bursill C.
        • et al.
        Colchicine acutely suppresses local cardiac production of inflammatory cytokines in patients with an acute coronary syndrome.
        J Am Heart Assoc. 2015; 4: e002128
        • Vaidya K.
        • Arnott C.
        • Martinez G.J.
        • Ng B.
        • McCormack S.
        • Sullivan D.R.
        • et al.
        Colchicine therapy and plaque stabilization in patients with acute coronary syndrome: a CT coronary angiography study.
        JACC Cardiovasc Imaging. 2018; 11: 305-316