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Colchicine in Patients With Coronary Artery Disease: A Systematic Review and Meta-Analysis of Randomized Trials.

ABSTRACT: Background Inflammation plays a pivotal role in coronary artery disease (CAD). The anti-inflammatory drug colchicine seems to reduce ischemic events in patients with CAD. So far there is equipoise about its safety and impact on mortality. Methods and Results To evaluate the utility of colchicine in patients with acute and chronic CAD, we performed a systematic review and meta-analysis. MEDLINE, EMBASE, Cochrane CENTRAL and conference abstracts were searched from January 1975 to October 2020. Randomized trials assessing colchicine compared with placebo/standard therapy in patients with CAD were included. Data were combined using random-effects models. The reliability of the available data was tested using trial sequential analyses . Of 3108 citations, 13 randomized trials (n=13 125) were included. Colchicine versus placebo/standard therapy in patients with CAD reduced risk of myocardial infarction (odds ratio [OR] 0.64; 95% CI, 0.46-0.90; P=0.01; I² 41%) and stroke/transient ischemic attack (OR 0.50; 95% CI, 0.31-0.81; P=0.005; I² 0%). But treatment with colchicine compared with placebo/standard therapy had no influence on all-cause and cardiovascular mortality (OR 0.96; 95% CI, 0.65-1.41; P=0.83; I² 24%; and OR 0.82; 95% CI, 0.55-1.22; P=0.45; I² 0%, respectively). Colchicine increased the risk for gastrointestinal side effects (P<0.001). According to trial sequential analyses, there is only sufficient evidence for a myocardial infarction risk reduction with colchicine. Conclusions Among patients with CAD, colchicine reduces the risk of myocardial infarction and stroke, but has a higher rate of gastrointestinal upset with no influence on all-cause mortality.

SUBMITTER: Kofler T

PROVIDER: S-EPMC8475038 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description: To critically evaluate the efficacy of renin angiotensin system inhibitors (RASi) in patients with coronary artery disease without heart failure, compared with active controls or placebo. Meta-analysis of randomized trials. PubMed, EMBASE, and CENTRAL databases until 1 May 2016. Randomized trials of RASi versus placebo or active controls in patients with stable coronary artery disease without heart failure (defined as left ventricular ejection fraction ?40% or without clinical heart failure). Each trial had to enroll at least 100 patients with coronary artery disease without heart failure, with at least one year's follow-up. Studies were excluded if they were redacted or compared use of angiotensin converting enzyme inhibitors with angiotensin receptor blockers. Outcomes were death, cardiovascular death, myocardial infarction, angina, stroke, heart failure, revascularization, incident diabetes, and drug withdrawal due to adverse effects. 24 trials with 198?275 patient years of follow-up were included. RASi reduced the risk of all cause mortality (rate ratio 0.84, 95% confidence interval 0.72 to 0.98), cardiovascular mortality (0.74, 0.59 to 0.94), myocardial infarction (0.82, 0.76 to 0.88), stroke (0.79, 0.70 to 0.89), angina, heart failure, and revascularization when compared with placebo but not when compared with active controls (all cause mortality, 1.05, 0.94 to 1.17; Pinteraction=0.006; cardiovascular mortality, 1.08, 0.93 to 1.25, Pinteraction<0.001; myocardial infarction, 0.99, 0.87 to 1.12, Pinteraction=0.01; stroke, 1.10, 0.93 to 1.31; Pinteraction=0.002). Bayesian meta-regression analysis showed that the effect of RASi when compared with placebo on all cause mortality and cardiovascular mortality was dependent on the control event rate, such that RASi was only beneficial in trials with high control event rates (>14.10 deaths and >7.65 cardiovascular deaths per 1000 patient years) but not in those with low control event rates. In patients with stable coronary artery disease without heart failure, RASi reduced cardiovascular events and death only when compared with placebo but not when compared with active controls. Even among placebo controlled trials in this study, the benefit of RASi was mainly seen in trials with higher control event rates but not in those with lower control event rates. Evidence does not support a preferred status of RASi over other active controls.

Project description:ObjectivesOver the years, it has been found that colchicine offers substantial benefits in secondary prevention in patients with coronary artery disease (CAD). We studied the effects of colchicine timing because there are no guidelines about when to provide it during the perioperative period for patients with CAD.MethodsUp to January 1, 2023, seven electronic literature databases were screened (including three English databases and four Chinese databases). Randomized controlled trials included only treatment with colchicine in the perioperative period of CAD. The Cochrane Evaluation Tool was used to judge the risk of bias in research. Statistical analysis was performed by Stata 16.0 software.ResultsWe evaluated twelve studies that found colchicine to be effective in decreasing the occurrence of major adverse cardiac events (MACEs) (p < 0.00001), but it also raised the rate of adverse events (p = 0.001). Subgroup analysis showed the same benefit in lowering the incidence of MACE with continuous administration of a total daily dose of 0.5 mg postoperatively while minimizing drug-related side effects in the patients (p = 0.03). When it comes to preventing surgical stroke occurrences, postoperative administration is more effective (p = 0.006). While the effect of simultaneous preoperative and postoperative administration was marginally greater than other periods in reducing postoperative hs-CRP levels (p = 0.02).ConclusionColchicine, a traditional anti-inflammatory drug, also reduces the risk of MACE by reducing inflammation after PCI. Administration at different periods had no significant effect on decreasing the occurrence of MACE, but when administered postoperatively, we advise continuous administration with a total daily dose of 0.5 mg to obtain the same benefit while minimizing the drug's side effects. Postoperative administration is the better measure to prevent postoperative stroke events. Due to the effective anti-inflammatory effect of colchicine, we recommend its use as early as possible in the perioperative period and its continued use at low doses in the postoperative period.Systematic review registrationhttps://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=316751, identifier CRD42022316751.

Project description:BACKGROUND:Colchicine has unique anti-inflammatory properties that may be beneficial in various cardiovascular conditions. This systematic review and meta-analysis of randomized controlled trials (RCTs) examines this issue. METHODS:We searched MEDLINE, EMBASE, and the Cochrane Database from inception to June 2014 for RCTs using colchicine in adult patients with cardiac diseases. Results were pooled using random effects. RESULTS:15 RCTs (n?=?3431 patients, median treatment 3 and follow-up 15 months) were included. All but 2 used colchicine 1 mg/day. In 5 trials, n?=?1301) at risk for cardiovascular disease (coronary artery disease, acute coronary syndrome or stroke, post-angioplasty [2 RCTs], or congestive heart failure), colchicine reduced composite cardiovascular outcomes by ~60 % (risk ratio [RR] 0.44, 95 % confidence interval [CI] 0.28-0.69, p?=?0.0004; I(2)?=?0 %) and showed a trend towards lower all-cause mortality (RR 0.50, 95 % CI 0.23-1.08, p?=?0.08; I(2)?=?0 %). In pericarditis or post-cardiotomy, colchicine decreased recurrent pericarditis or post-pericardiotomy syndrome (RR 0.50, 95 % CI 0.41-0.60, p?<?0.0001; I(2)?=?0 %; 8 RCTs, n?=?1635), and post-pericardiotomy or ablation induced atrial fibrillation (RR 0.65, 95 % CI 0.51-0.82, p?=?0.0003; I(2)?=?31 %; 4 RCTs, n?=?1118). The most common adverse event was diarrhea. Treatment discontinuation overall and due to adverse events (RR 4.34, 95 % CI 1.70-11.07, p?=?0.002; I(2)?=?29 %; 7 RCTs, 83/790 [10.5 %] vs. 11/697 [1.6 %]) was higher in colchicine-assigned patients. CONCLUSIONS:Current RCT data suggests that colchicine may reduce the composite rate of cardiovascular adverse outcomes in a range of patients with established cardiovascular disease. Furthermore, colchicine reduces rates of recurrent pericarditis, post-pericardiotomy syndrome, and peri-procedural atrial fibrillation following cardiac surgery. Further RCTs evaluating the potential of colchicine for secondary prevention of cardiovascular events would be of interest.

Project description: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].

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Colchicine in Patients With Coronary Artery Disease: A Systematic Review and Meta-Analysis of Randomized Trials.

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