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Published on: August 18, 2016
Colchicine in Patients with Chronic Coronary Disease
Stefan M Nidorf1, Aernoud T L Fiolet1, Arend Mosterd1
1From GenesisCare Western Australia (S.M.N., X.-F.X., M.A.I., D.L., A.W., R.H., P.S., I.T., A.G.T., A. Morton, P.L.T.), the Heart and Vascular Research Institute (S.M.N., P.L.T.) and the Department of Neurology (G.J.H.), Sir Charles Gairdner Hospital, and the Faculty of Health and Medical Sciences (G.J.H., P.L.T.) and the School of Population and Global Health (C.A.B.), University of Western Australia, Perth, the Department of Cardiology, Fiona Stanley Hospital, Murdoch, WA (C.J.), and the Harry Perkins Institute of Medical Research, Nedlands, WA (P.L.T.) - all in Australia; the Dutch Network for Cardiovascular Research (A.T.L.F., A. Mosterd, A.S., S.H.K.T., T.L., P.H., A.J., P.N., H.S., J.S., A.F.M.K., M.W.J.H., M.D., M.A., J.H.C.), the Netherlands Heart Institute (A.T.L.F.), and the Department of Cardiology (A.T.L.F.) and the Julius Center for Health Sciences and Primary Care (A. Mosterd, M.A.), University Medical Center Utrecht, Utrecht, the Department of Cardiology, Meander Medical Center, Amersfoort (A. Mosterd), the Departments of Cardiology (T.S.J.O., M.D., J.H.C.) and Internal Medicine (W.A.B.), Northwest Clinics, Alkmaar, the Department of Cardiology, Radboud University Medical Center, Nijmegen (T.S.J.O., J.H.C.), the Department of Cardiology, Treant Zorggroep, Hoogeveen, Emmen, and Stadskanaal (S.H.K.T.), the Department of Cardiology, Zuyderland Medical Center, Heerlen and Sittard (T.L.), the Department of Cardiology, Isala Diaconessenhuis, Meppel (P.H.), the Department of Cardiology, Gelre Hospitals, Apeldoorn (A.J.), the Department of Cardiology, Franciscus Hospital (P.N.), and Cardialysis (J.G.P.T.), Rotterdam, the Department of Cardiology, D&A Research and Genetics, Sneek (H.S.), the Department of Cardiology, Amphia and Breda (J.S., M.A.), the Department of Cardiology, Spaarne Hospital, Haarlem and Hoofddorp (A.F.M.K.), the Department of Cardiology, Green Heart Hospital, Gouda (M.W.J.H.), and the Department of Cardiology, Amsterdam UMC, Amsterdam (J.G.P.T.) - all in the Netherlands; and the Department of Medicine, McMaster University, Hamilton, ON, Canada (J.W.E.).
Insights
Colchicine significantly reduced cardiovascular events in patients with chronic coronary disease. This anti-inflammatory drug offers a new therapeutic option for managing coronary artery disease risks.
Area of Science:
- Cardiology
- Pharmacology
- Inflammation
Background:
- Limited evidence existed for colchicine's cardiovascular benefits in chronic coronary disease.
- Previous trials suggested anti-inflammatory effects reduce events post-myocardial infarction.
Purpose of the Study:
- To evaluate the efficacy of daily low-dose colchicine in reducing cardiovascular events in patients with chronic coronary disease.
- To assess the impact of colchicine on major adverse cardiovascular outcomes.
Main Methods:
- A randomized, controlled, double-blind trial design was employed.
- 5522 patients with chronic coronary disease were randomized to receive either 0.5 mg colchicine daily or a placebo.
- The primary endpoint was a composite of cardiovascular death, myocardial infarction, ischemic stroke, or revascularization.
Main Results:
- Colchicine significantly reduced the primary composite endpoint by 31% (hazard ratio, 0.69; P<0.001).
- Key secondary endpoints, including cardiovascular death, myocardial infarction, or ischemic stroke, were also significantly lower in the colchicine group (hazard ratio, 0.72; P=0.007).
- Higher incidence of noncardiovascular deaths was observed in the colchicine group.
Conclusions:
- Daily low-dose colchicine effectively reduces the risk of major cardiovascular events in patients with chronic coronary disease.
- Colchicine represents a promising anti-inflammatory therapeutic strategy for secondary prevention in coronary artery disease.
- Further research is warranted to balance benefits against potential risks like noncardiovascular mortality.
Background:
Evidence from a recent trial has shown that the antiinflammatory effects of colchicine reduce the risk of cardiovascular events in patients with recent myocardial infarction, but evidence of such a risk reduction in patients with chronic coronary disease is limited.
Methods:
In a randomized, controlled, double-blind trial, we assigned patients with chronic coronary disease to receive 0.5 mg of colchicine once daily or matching placebo. The primary end point was a composite of cardiovascular death, spontaneous (nonprocedural) myocardial infarction, ischemic stroke, or ischemia-driven coronary revascularization. The key secondary end point was a composite of cardiovascular death, spontaneous myocardial infarction, or ischemic stroke.
Results:
A total of 5522 patients underwent randomization; 2762 were assigned to the colchicine group and 2760 to the placebo group. The median duration of follow-up was 28.6 months. A primary end-point event occurred in 187 patients (6.8%) in the colchicine group and in 264 patients (9.6%) in the placebo group (incidence, 2.5 vs. 3.6 events per 100 person-years; hazard ratio, 0.69; 95% confidence interval [CI], 0.57 to 0.83; P<0.001). A key secondary end-point event occurred in 115 patients (4.2%) in the colchicine group and in 157 patients (5.7%) in the placebo group (incidence, 1.5 vs. 2.1 events per 100 person-years; hazard ratio, 0.72; 95% CI, 0.57 to 0.92; P = 0.007). The incidence rates of spontaneous myocardial infarction or ischemia-driven coronary revascularization (composite end point), cardiovascular death or spontaneous myocardial infarction (composite end point), ischemia-driven coronary revascularization, and spontaneous myocardial infarction were also significantly lower with colchicine than with placebo. The incidence of death from noncardiovascular causes was higher in the colchicine group than in the placebo group (incidence, 0.7 vs. 0.5 events per 100 person-years; hazard ratio, 1.51; 95% CI, 0.99 to 2.31).
Conclusions:
In a randomized trial involving patients with chronic coronary disease, the risk of cardiovascular events was significantly lower among those who received 0.5 mg of colchicine once daily than among those who received placebo. (Funded by the National Health Medical Research Council of Australia and others; LoDoCo2 Australian New Zealand Clinical Trials Registry number, ACTRN12614000093684.).
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