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

Abstract

BackgroundSeveral 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.MethodsRandomized 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.ResultsThis 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.ConclusionColchicine 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].

Frontiers and hotspots evolution in anti-inflammatory studies for coronary heart disease: A bibliometric analysis of 1990–2022

“…Colchicine may be beneficial as an additional secondary prevention drug in patients post-ACS. Recent meta-analyses ( 139 – 142 ) have shown that colchicine positively reduces the incidence of MACE, MI, stroke, and revascularization and decreases cardiovascular events, inflammatory markers, hs-CRP, and IL-6 in patients with coronary artery disease. But with a higher incidence of gastrointestinal distress and no effect on all-cause mortality.…”

Efficacy and Safety of Different Dosing Regimens of Colchicine in Patients With Coronary Artery Disease: A Network Meta-analysis of 15 Randomized Controlled Trials

“… 66 , 67 Nevertheless, such benefits were not attributed to a mortality benefit in this network meta-analysis, which was consistent with the findings of previous meta-analyses. 20 , 63 , 68 It should not be ignored that various disease types were evaluated in eligible studies, therefore inevitably introducing bias to compromise mortality benefit. Moreover, we cannot also eliminate the influence of variations in follow-up durations on mortality.…”

“…To date, many conventional pairwise meta-analyses have systematically evaluated and consistently established the effects and safety of colchicine for the treatment of patients with CAD [19][20][21][22][23][24][25][26]63,68,69 ; however, all these findings from previous meta-analyses did not inform practitioners which dosing regimen may be preferred for these patients. Given this open issue, the current network meta-analysis rationally classified colchicine dose into 3 regimens based on published evidence 26 and first determined the comparative efficacy and safety among 3 dosing regimens.…”

“…14,[16][17][18] Moreover, several meta-analyses have also confirmed the role of colchicine in patients with CAD. [19][20][21][22][23][24][25] However, multiple colchicine doses are used in practice, including low dose (0.5 mg once daily), high dose (1.0 mg once daily or 0.5 mg twice daily), and loading dose (initial dose plus a subsequent loading dose), and the optimal dose has been debated. 19,25,26 Therefore, this study used network meta-analysis to comprehensively evaluate the comparative efficacy and safety of 3 dosing regimens of colchicine in patients with CAD.…”

Colchicine in atrial fibrillation: are old trees in bloom?

“…A number of meta-analyses have demonstrated the positive effects of LoDoCo on the prognosis of patients with coronary heart disease, such as a significant reduction in cardiovascular mortality, myocardial infarction, and stroke ( Samuel et al, 2021a ; Samuel et al, 2021b ; Xia et al, 2021 ; Ma et al, 2022 ). The systematic review by Samuel et al also supported this result ( Fiolet et al, 2021 ).…”