Colchicine and coronary heart disease risks: A meta-analysis of randomized controlled clinical trials

BACKGROUND: Several trials have considered the safety and clinical benefits of colchicine as a treatment option for secondary prevention in patients with coronary atherosclerotic heart disease (CAD), but its safety and clinical benefits remain controversial. The purpose of this study was to explore the clinical benefits of colchicine, focusing on certain subgroups of patients. METHODS: Randomized controlled trials (RCTs) of colchicine in subjects with acute or chronic CAD compared with controls were included to assess all-cause mortality, non-cardiovascular mortality, gastrointestinal adverse effects, diarrhea, MACE, cardiovascular mortality, MI, stroke, and revascularization. We analyzed the association of cardiovascular, mortality, and gastrointestinal risk with colchicine in all subjects. We also focused on the cardiovascular risk of colchicine in subgroups with different drug doses, different treatment durations, age, gender, and associated comorbidities. RESULTS: This meta-analysis included 15 clinical RCTs, including 13,539 subjects. Colchicine reduced the risk of MACE (RR: 0.65; 95% CI: 0.38–0.77, p for heterogeneity < 0.01; I2 = 70%; p < 0.01), stroke (RR: 0.48; 95% CI: 0.30–0.76; p heterogeneity = 0.52; I2 = 0%; p < 0.01), MI by 40% (RR: 0.60; 95% CI: 0.43–0.83; p for heterogeneity = 0.01; I2 = 59%; p < 0.01) and risk of revascularization (RR: 0.68; 95% CI: 0.56–0.83; p for heterogeneity = 0.17; I2 = 40%; p < 0.01), but had no significant effect on risk of cardiovascular death and risk of all-cause mortality. In addition, colchicine increased the risk of gastrointestinal side effects and diarrhea. In a subgroup analysis, low-dose colchicine and treatment duration > 1 month reduced the risk of MACE, MI, stroke, and revascularization. Also, the cardiovascular benefits of colchicine were observed in subjects up to 65 years of age. The results showed that hypertension and diabetes did not have a specific effect on colchicine and MACE risk. CONCLUSION: Colchicine has a positive effect in reducing the incidence of MACE, MI, stroke, and revascularization, but can increase the risk of gastrointestinal and diarrhea events. Low-dose colchicine significantly reduces the risk of MACE more than high-dose colchicine, and the benefits of long-term treatment are higher than those of short-term treatment. Long-term low-dose colchicine treatment may significantly reduce the risk of cardiovascular events. Furthermore, colchicine significantly reduced the risk of cardiovascular events in patients up to 65 years of age, but it did not appear to reduce cardiovascular risk in patients over 65 years of age or in preoperative PCI patients. SYSTEMATIC REVIEW REGISTRATION: [https://www.crd.york.ac.uk/prospero/], identifier [CDR42022332170].