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1.
Int J Rheum Dis ; 27(5): e15162, 2024 May.
Article in English | MEDLINE | ID: mdl-38720421

ABSTRACT

BACKGROUND: Recent findings suggest a link between gout and the development of dementia. Early treatment with colchicine is recommended as a first-line therapy for gout flares. Animal studies demonstrate that colchicine could induce cognitive impairment. This cohort study aimed to investigate the association between colchicine use and the risk of developing dementia. METHODS: In this nationwide cohort study, we performed comparative analysis on 6147 patients ≥40 years, with gout and colchicine new users against 6147 controls to assess subsequent dementia risk. The colchicine group and the control group (urate lowering therapy group) were matched on the bases of age, sex, index year, and comorbidities. All participants were followed for up to 14 years for a diagnosis of dementia considering medical records were retrospectively checked over this period. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). Sensitivity analyses were performed to validate our findings. RESULTS: The adjusted hazard ratio (aHR) of dementia for colchicine users was 1.45 (95% CI = 1.05, 1.99) relative to comparison group after adjusting for sex, age, and comorbidities. Sensitivity analysis aiming to minimize underdiagnosed occult dementia at the time of index year yielded consistent positive association. In higher accumulative dose colchicine group (cumulative defined daily dose [cDDD] >30), the aHR of dementia risk for colchicine users was 1.42 (95% CI = 1.03, 1.97) compared with nonusers. For those duration of colchicine use >30 days, the aHR was 1.53 (95% CI = 1.01-2.32) compared to the nonuser group. CONCLUSIONS: A significant risk of dementia was observed in this study in patients with gout using colchicine at higher cDDD and for a longer period. Further research is needed to elucidate the relationship between colchicine, gout, and dementia.


Subject(s)
Colchicine , Dementia , Gout Suppressants , Gout , Humans , Colchicine/adverse effects , Colchicine/therapeutic use , Gout/epidemiology , Gout/drug therapy , Dementia/epidemiology , Dementia/chemically induced , Dementia/diagnosis , Female , Male , Retrospective Studies , Aged , Middle Aged , Gout Suppressants/adverse effects , Risk Factors , Risk Assessment , Time Factors , Taiwan/epidemiology , Adult , Aged, 80 and over , Databases, Factual
2.
Trials ; 25(1): 229, 2024 Apr 03.
Article in English | MEDLINE | ID: mdl-38570873

ABSTRACT

BACKGROUND: To date, colchicine and prednisolone are two effective therapies for the treatment of acute gout but have never been compared directly in a randomized clinical trial. In addition, in previous trials of treating acute gout patients with concomitant comorbidities were often excluded due to contraindications to naproxen. STUDY DESIGN: This pragmatic, prospective, double-blind, double-dummy, parallel-group, randomized, non-inferiority trial compares prednisolone with colchicine in terms of non-inferiority in patients with acute gout. Patients presenting to their general practitioner with acute gout can be included if the gout attack has occurred within the last 2 days. A total of 60 practices in the vicinity of three university medical centers (Greifswald, Göttingen, and Würzburg) participate in the study. The intervention group receives 30 mg prednisolone for 5 days, while the group of standard care receives low-dose colchicine (day 1: 1.5 mg; days 2-5: 1 mg). The first dose of treatment is provided at day 0 when patients present to the general practitioner due to an acute gout attack. From day 0 to day 6, patients will be asked to complete a study diary on daily basis regarding pain quantification. For safety reasons, potential side effects and the course of systolic blood pressure are also assessed. STATISTICAL ANALYSIS PLAN: N = 314 patients have to be recruited to compensate for 10% of dropout and to allow for showing non-inferiority of prednisolone compared to colchicine with a power of 90%. We use permuted block randomization with block sizes of 2, 4, and 6 to avoid imbalanced treatment arms in this multi-center study; patients are randomized in a 1:1 ratio. The absolute level of pain on day 3 (in the last 24 h) is the primary outcome and measured on a numerical rating scale (NRS: 0-10). Using a multiple linear regression model adjusted for age, sex, and pain at baseline, prednisolone is considered non-inferior if the effect estimate including the confidence intervals is lower than a margin of 1 unit on the NRS. Average response to treatment, joint swelling and tenderness, physical function of the joint, and patients' global assessment of treatment success are secondary outcomes. DISCUSSION: The trial will provide evidence from a direct comparison of colchicine and prednisolone regarding their efficacy of pain reduction in acute gout patients of primary care and to indicate possible safety signals. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05698680 first posted on January 26, 2023 (retrospectively registered).


Subject(s)
Arthritis, Gouty , Gout , Humans , Arthritis, Gouty/drug therapy , Colchicine/adverse effects , Gout/diagnosis , Gout/drug therapy , Pain , Prednisolone/adverse effects , Primary Health Care , Prospective Studies , Treatment Outcome , Male , Female
3.
Int Immunopharmacol ; 132: 111967, 2024 May 10.
Article in English | MEDLINE | ID: mdl-38569431

ABSTRACT

OBJECTIVES: Canakinumab, a human monoclonal antibody targeted at interleukin-1 beta, has demonstrated safety and efficacy in preventing familial Mediterranean fever (FMF) attacks among individuals with colchicine-resistant (crFMF). The manufacturer orders prescribe monthly subcutaneous injections. However, a subset of our patients is treated with an "canakinumab on demand " (COD) strategy, with wider intervals between drug administrations. Therefore, we aimed to compare disease activity and drug safety between COD and "canakinumab fixed frequency" (CFF) policies. METHODS: This retrospective study collected data from three Israeli paediatric rheumatology centres, of children with crFMF who were treated with canakinumab. Epidemiological and clinical parameters, cumulative drug dosages, and adverse events were compared between children treated by both policies. RESULTS: Twenty-five (49 %) children were treated according to COD policy and 26 according to CFF policy. Demographic parameters and most of the disease features did not differ significantly between the groups. Both groups showed significant reduction in attacks after canakinumab introduction. The median number (interquartile range) of attacks per month did not differ significantly between the COD and CFF groups (0.33 (0.08, 0.58) and 0.13 (0, 0.5), respectively, p = 0.485 (even though, per definition, COD patients presumably had an attack before receiving the second canakinumab dose). The mean monthly dose was lower for the COD than the CFF group (1.13 ± 1.13 vs. 3.16 ± 1.46 mg/kg, p < 0.001). Adverse events were similar between the groups. CONCLUSION: For individuals with crFMF, COD compared to CFF policy can achieve similar efficacy and safety, with a lower accumulated canakinumab dose, rendering it less immunosuppressive and less expensive.


Subject(s)
Antibodies, Monoclonal, Humanized , Colchicine , Drug Resistance , Familial Mediterranean Fever , Humans , Familial Mediterranean Fever/drug therapy , Antibodies, Monoclonal, Humanized/therapeutic use , Antibodies, Monoclonal, Humanized/adverse effects , Antibodies, Monoclonal, Humanized/administration & dosage , Child , Male , Female , Retrospective Studies , Colchicine/therapeutic use , Colchicine/administration & dosage , Colchicine/adverse effects , Adolescent , Interleukin-1beta/antagonists & inhibitors , Interleukin-1beta/immunology , Treatment Outcome , Child, Preschool , Israel , Drug Administration Schedule
4.
Eur Heart J ; 45(18): 1596-1601, 2024 May 13.
Article in English | MEDLINE | ID: mdl-38596868

ABSTRACT

Low-dose colchicine (0.5 mg daily) is now FDA-approved for secondary prevention in patients with coronary disease and will be increasingly prescribed in clinical practice. In this State-of-the-Art Review, data were collated from contemporary systemic reviews of case reports, drug registries, and placebo-controlled trials that assessed specific issues of safety related to the continuous use of colchicine in a range of clinical settings to inform physicians, pharmacists, and patients of the absolute risks of continuous use of low-dose colchicine, including among individuals taking statin therapy. Based upon these collective data, it is concluded that aside mild diarrhoea on initiation of colchicine that typically subsides in the vast majority of patients within a week of therapy, continuous use of low-dose colchicine is well tolerated and very safe. It does not affect renal, liver, or cognitive function, has no adverse effects on bleeding, wound healing, fertility, or pregnancy, and does not increase risks of cancer, serious infection, or cause-specific mortality. When appropriately prescribed to patients without significant renal or hepatic impairment, reports of myelosuppression, myotoxicity, and serious drug-drug interactions are rare and no more frequent than placebo, including in patients taking statin therapy. Physicians, pharmacists, and patients can be reassured that in the absence of significant renal or hepatic impairment continuous use of low-dose colchicine can be used safely in patients with atherosclerosis for the purpose of reducing cardiovascular risk.


Subject(s)
Colchicine , Colchicine/administration & dosage , Colchicine/adverse effects , Humans , Atherosclerosis/drug therapy , Atherosclerosis/prevention & control , Drug Interactions , Female , Hydroxymethylglutaryl-CoA Reductase Inhibitors/administration & dosage , Hydroxymethylglutaryl-CoA Reductase Inhibitors/adverse effects , Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use
5.
Int J Cardiol ; 406: 132068, 2024 Jul 01.
Article in English | MEDLINE | ID: mdl-38648916

ABSTRACT

BACKGROUND: Atrial fibrillation (AF), the most common arrhythmia, is closely related to inflammation. Colchicine has the potent anti-inflammatory effects. Several randomized clinical trials (RCTs) have evaluated the efficacy and safety of colchicine in the prevention of AF but the results are inconsistent. OBJECTIVE: The purpose of our study was to evaluate the impact of colchicine on AF. METHOD AND RESULTS: PubMed, EMBASE, Web of Science, Cochrane Library and ClinicalTrials.gov were searched for related studies until Jan 8, 2024. A total of 17 studies including 16,238 participants were included. Compared to the placebo group, there were fewer incidences of AF in the colchicine group (RR: 0.75, 95%CI: 0.68-0.83, P < 0.001). The incidence of overall adverse events and overall gastrointestinal intolerance did not differ significantly between the two groups. However, diarrhea, nausea, and discontinuation occurred more frequently in patients treated with colchicine. CONCLUSION: Colchicine can prevent patients from the incidence of AF, regardless of the mean age of patients, type of atrial fibrillation, maintenance dose, duration of colchicine use, cumulative daily dose, and follow-up time with more diarrhea, nausea and discontinuation. These adverse events can be avoided by low doses (0.5 mg once daily) and long period time of colchicine use.


Subject(s)
Atrial Fibrillation , Colchicine , Randomized Controlled Trials as Topic , Colchicine/therapeutic use , Colchicine/adverse effects , Atrial Fibrillation/prevention & control , Atrial Fibrillation/drug therapy , Humans , Randomized Controlled Trials as Topic/methods , Treatment Outcome
6.
Int J Cardiovasc Imaging ; 40(4): 945-948, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38558330

ABSTRACT

In the last century, there has been more than enough research that proved the association of high lipid and glucose levels with cardiovascular disease, thus establishing the current well-known traditional cardiovascular risk factors such as dyslipidemia, diabetes, and metabolic syndrome. Hence, these cardiovascular risk factors are target therapy for glucose and lipid-lowering agents to prevent adverse cardiovascular events. However, despite controlling the lipid and glucose levels, some studies demonstrated the subclinical atherosclerosis suggesting that these cardiovascular risk factors alone cannot account for the entire atherosclerosis burden. In the last years, large-scale clinical trials demonstrated the operation of the inflammatory pathway in atherosclerotic cardiovascular disease (ASCVD) by the immune system, both the innate (neutrophils, macrophages) and adaptive (T cell and other lymphocytes) limbs, contribute to atherosclerosis and atherothrombosis. In this regard, some studies that use antiinflammatory therapy targeting the immune system by modulating or blocking interleukins, also known as anti-cytokine therapy, have been shown to reduce the risk of adverse cardiovascular events in patients with previous coronary artery disease. In this regard, the U.S. Food and Drug Administration (FDA) approved the use of colchicine 0.5 mg once daily for reducing cardiovascular events in patients who have established ASCVD and high residual systemic inflammation. Therefore, measuring the systemic inflammation can improve the cardiovascular risk assessment and identify the subsets of patients that will benefit from anti-cytokine therapy after diagnosis of ASCVD or after myocardial revascularization.


Subject(s)
Anti-Inflammatory Agents , Biomarkers , Blood Glucose , Cytokines , Heart Disease Risk Factors , Inflammation Mediators , Inflammation , Triglycerides , Humans , Anti-Inflammatory Agents/therapeutic use , Anti-Inflammatory Agents/adverse effects , Atherosclerosis/immunology , Atherosclerosis/drug therapy , Atherosclerosis/blood , Biomarkers/blood , Blood Glucose/drug effects , Blood Glucose/metabolism , Cardiovascular Diseases/prevention & control , Cardiovascular Diseases/immunology , Colchicine/therapeutic use , Colchicine/adverse effects , Cytokines/blood , Cytokines/metabolism , Inflammation/immunology , Inflammation/drug therapy , Inflammation/blood , Inflammation Mediators/blood , Inflammation Mediators/metabolism , Risk Assessment , Risk Factors , Treatment Outcome , Triglycerides/blood
7.
Open Heart ; 11(1)2024 Mar 15.
Article in English | MEDLINE | ID: mdl-38490715

ABSTRACT

AIM: Anakinra, an anti IL-1 agent targeting IL-1 alfa and beta, is available for the treatment of recurrent pericarditis in cases with corticosteroid dependence and colchicine resistance after failure of conventional therapies. However, it is unclear if the combination with colchicine, a non-specific inhibitor of the inflammasome targeting the same inflammatory pathway of IL-1, could provide additional benefit to prevent further recurrences. The aim of the present observational study is to assess whether the addition of colchicine on top of anakinra could prolong the time to first recurrence and prevent recurrences better than anakinra alone. METHODS: International, all-comers, multicentre, retrospective observational cohort study analysing all consecutive patients treated with anakinra for corticosteroid-dependent and colchicine-resistant recurrent pericarditis. The efficacy endpoint was recurrence rate and the time to the first recurrence. RESULTS: A total of 256 patients (mean age 45.0±15.4 years, 65.6% females, 80.9% with idiopathic/viral aetiology) were included. 64 (25.0%) were treated with anakinra as monotherapy while 192 (75.0%) with both anakinra and colchicine. After a follow-up of 12 months, 56 (21.9%) patients had recurrences. Patients treated with colchicine added to anakinra had a lower incidence of recurrences (respectively, 18.8% vs 31.3%; p=0.036) and a longer event-free survival (p=0.025). In multivariable analysis, colchicine use prevented recurrences (HR 0.52, 95% CI 0.29 to 0.91; p=0.021). CONCLUSIONS: The addition of colchicine on top of anakinra treatment could be helpful to reduce recurrences and prolong the recurrence-free survival.


Subject(s)
Interleukin 1 Receptor Antagonist Protein , Pericarditis , Female , Humans , Adult , Middle Aged , Male , Interleukin 1 Receptor Antagonist Protein/adverse effects , Retrospective Studies , Colchicine/adverse effects , Adrenal Cortex Hormones , Pericarditis/diagnosis , Pericarditis/drug therapy , Pericarditis/chemically induced , Interleukin-1
8.
J Interv Cardiol ; 2024: 8646351, 2024.
Article in English | MEDLINE | ID: mdl-38505729

ABSTRACT

Background: Colchicine has shown potential cardioprotective effects owing to its broad anti-inflammatory properties. We performed a meta-analysis to assess its safety and efficacy in secondary prevention in patients with established coronary artery disease (CAD). Methods: We searched Ovid Healthstar, MEDLINE, and Embase (inception to May 2022) for randomized controlled trials (RCTs) evaluating the cardiovascular effects of colchicine compared with placebo or usual care in patients with CAD. Study-level data on efficacy and safety outcomes were pooled using the Peto method. The primary outcome was the composite of cardiovascular (CV) death, myocardial infarction (MI), or stroke. Results: A total of 8 RCTs were included with a follow-up duration of ≥1 month, comprising a total of 12,151 patients. Compared with placebo or usual care, colchicine was associated with a significant risk reduction in the primary outcome (odds ratio (OR) 0.70, 95% CI 0.60 to 0.83, P < 0.0001; I2 = 52%). Risks of MI (OR 0.75, 95% CI 0.62 to 0.91, P = 0.003; I2 = 33%), stroke (OR 0.47, 95% CI 0.30 to 0.74, P = 0.001; I2 = 0%), and unplanned coronary revascularization (OR 0.67, 95% CI 0.55 to 0.82, P = 0.0001; I2 = 58%) were all reduced in the colchicine group. Rates of CV and all-cause mortality did not differ between the two groups, but there was an increase in noncardiac deaths with colchicine (OR 1.54, 95% CI 1.10 to 2.15, P = 0.01; I2 = 51%). The occurrence of all other adverse events was similar between the two groups, including GI reactions (OR 1.06, 95% CI 0.94 to 1.20, P = 0.35; I2 = 42%) and infections (OR 1.04, 95% CI 0.84 to 1.28, P = 0.74; I2 = 53%). Conclusions: Colchicine therapy may reduce the risk of future cardiovascular events in patients with established CAD; however, there remains a concern about non-CV mortality. Further trials are underway that will shed light on non-CV mortality and colchicine NCT03048825, and NCT02898610.


Subject(s)
Cardiovascular Diseases , Coronary Artery Disease , Myocardial Infarction , Stroke , Humans , Cardiovascular Diseases/prevention & control , Colchicine/adverse effects , Secondary Prevention , Randomized Controlled Trials as Topic , Myocardial Infarction/epidemiology , Stroke/prevention & control , Stroke/epidemiology , Coronary Artery Disease/drug therapy
9.
Arterioscler Thromb Vasc Biol ; 44(5): 1031-1041, 2024 May.
Article in English | MEDLINE | ID: mdl-38511324

ABSTRACT

Colchicine-an anti-inflammatory alkaloid-has assumed an important role in the management of cardiovascular inflammation ≈3500 years after its first medicinal use in ancient Egypt. Primarily used in high doses for the treatment of acute gout flares during the 20th century, research in the early 21st century demonstrated that low-dose colchicine effectively treats acute gout attacks, lowers the risk of recurrent pericarditis, and can add to secondary prevention of major adverse cardiovascular events. As the first Food and Drug Administration-approved targeted anti-inflammatory cardiovascular therapy, colchicine currently has a unique role in the management of atherosclerotic cardiovascular disease. The safe use of colchicine requires careful monitoring for drug-drug interactions, changes in kidney and liver function, and counseling regarding gastrointestinal upset. Future research should elucidate the mechanisms of anti-inflammatory effects of colchicine relevant to atherosclerosis, the potential role of colchicine in primary prevention, in other cardiometabolic conditions, colchicine's safety in cardiovascular patients, and opportunities for individualizing colchicine therapy using clinical and molecular diagnostics.


Subject(s)
Cardiovascular Diseases , Colchicine , Humans , Anti-Inflammatory Agents/therapeutic use , Anti-Inflammatory Agents/adverse effects , Cardiovascular Diseases/drug therapy , Cardiovascular Diseases/prevention & control , Colchicine/therapeutic use , Colchicine/adverse effects , Drug Interactions , Gout Suppressants/therapeutic use , Gout Suppressants/adverse effects , Treatment Outcome
10.
Arthritis Care Res (Hoboken) ; 76(6): 871-881, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38303574

ABSTRACT

OBJECTIVE: We systematically examined comparative gout flare risk after initiation or escalation of different urate-lowering therapies (ULTs), comparative flare risk with and without concomitant flare prophylaxis, adverse event rates associated with flare prophylaxis, and optimal duration of flare prophylaxis. METHODS: We searched the Medline, Embase, Web of Science, and Cochrane databases and clinical trial registries from inception to November 2021 for trials investigating adults with gout initiating or escalating ULT. We performed random effects network meta-analyses and calculated risk ratios (RRs) between treatments. Bias was assessed using the revised Cochrane risk-of-bias tool. RESULTS: We identified 3,775 records, of which 29 publications (27 trials) were included. When compared to placebo plus prophylaxis, the RR of flares ranged from 1.08 (95% confidence interval [CI] 0.87-1.33) for febuxostat 40 mg plus prophylaxis to RR 2.65 [95% CI 1.58-4.45] for febuxostat 80 mg plus lesinurad 400 mg plus prophylaxis. Compared to ULT alone, the RR of flares was lower for ULT plus rilonacept 160 mg (RR 0.35 [95% CI 0.25-0.50]), ULT plus rilonacept 80 mg (RR 0.43 [95% CI 0.31-0.60]) and ULT plus colchicine (RR 0.50 [95% CI 0.35-0.72]). There was limited evidence for other flare prophylaxis and on prophylaxis harms and optimal duration. Primarily because of missing outcome data and bias in the selection of reported results, 71.4% and 63.4% of studies were assessed as high risk of bias for flares and adverse events, respectively. CONCLUSION: The RR of flares when introducing ULT varies depending on ULT drug and dosing strategies. There were limited data on ULT escalation. Flare prophylaxis with colchicine and rilonacept reduces flare incidence. More research is required on the harms and optimal duration of prophylaxis.


Subject(s)
Gout Suppressants , Gout , Network Meta-Analysis , Symptom Flare Up , Uric Acid , Humans , Gout/drug therapy , Gout/blood , Gout Suppressants/therapeutic use , Gout Suppressants/adverse effects , Gout Suppressants/administration & dosage , Uric Acid/blood , Risk Assessment , Colchicine/therapeutic use , Colchicine/adverse effects , Colchicine/administration & dosage , Febuxostat/therapeutic use , Febuxostat/administration & dosage , Febuxostat/adverse effects , Treatment Outcome , Risk Factors , Drug Therapy, Combination , Recombinant Fusion Proteins
11.
Heart ; 110(10): 735-739, 2024 Apr 25.
Article in English | MEDLINE | ID: mdl-38238076

ABSTRACT

OBJECTIVE: Clinical trials have evaluated the efficacy and safety of colchicine only in simple pericarditis, excluding cases of concomitant myocarditis. The aim of this paper is to evaluate the efficacy and safety of colchicine for the treatment of the first attack of acute pericarditis with concomitant myocardial involvement. METHODS: Double-centre retrospective cohort study analysing consecutive patients admitted for first attack of pericarditis with myocarditis and treated with or without colchicine. The primary efficacy end point was the time to the first recurrence. Propensity score matching was used to generate two groups of patients with similar baseline characteristics. Colchicine-associated side effects were analysed as safety end-point. RESULTS: A total of 175 patients (mean age 46.2±20.1 years, 25.1% females, 88.6% with idiopathic/viral aetiology) were included. Seventy-nine (45.1%) patients were treated with colchicine. After a median follow-up of 25.3 (IQR 8.3-45.6) months, 58 (33.1%) patients had recurrences. The propensity score generated two groups of 73 patients with similar baseline characteristics but the use of colchicine. Patients treated with colchicine had a lower incidence of recurrences (respectively, 19.2% vs 43.8%; p=0.001) and a longer event-free survival (p=0.005). In multivariable analysis, women (HR 1.97, 95% CI 1.04 to 3.73; p=0.037) and corticosteroid use (HR 2.27, 95% CI 1.15 to 4.47; p=0.018) were independent risk factors for recurrences. Colchicine-associated side effects were mild and occurred in 3 (1.7%) patients. CONCLUSION: In patients with first attack of pericarditis associated with myocardial involvement, colchicine was safe and efficacious for the reduction of recurrences.


Subject(s)
Colchicine , Myocarditis , Pericarditis , Recurrence , Adult , Female , Humans , Male , Middle Aged , Acute Disease , Colchicine/therapeutic use , Colchicine/adverse effects , Disease-Free Survival , Myocarditis/drug therapy , Pericarditis/drug therapy , Propensity Score , Retrospective Studies , Treatment Outcome , Tubulin Modulators/therapeutic use , Tubulin Modulators/adverse effects
12.
Diabetes Care ; 47(3): 467-470, 2024 Mar 01.
Article in English | MEDLINE | ID: mdl-38181203

ABSTRACT

OBJECTIVE: The cardiovascular benefits of low-dose colchicine have been demonstrated in patients with coronary disease. Its effects were evaluated in this prespecified analysis in patients with type 2 diabetes (T2D) from the Colchicine Cardiovascular Outcomes Trial (COLCOT). RESEARCH DESIGN AND METHODS: COLCOT was a randomized, double-blinded trial of colchicine, 0.5 mg daily, versus placebo initiated within 30 days after a myocardial infarction. RESULTS: There were 959 patients with T2D enrolled and monitored for a median of 22.6 months. A primary end point event occurred in 8.7% of patients in the colchicine group and in 13.1% in the placebo group (hazard ratio 0.65; 95% CI 0.44-0.96; P = 0.03). Nausea was reported in 2.7% and 0.8% in the study groups (P = 0.03), and pneumonia occurred in 2.4% and 0.4% (P = 0.008). CONCLUSIONS: Among patients with T2D and a recent myocardial infarction, colchicine, 0.5 mg daily, leads to a large reduction of cardiovascular events. These results support the conduct of the COLCOT-T2D trial in primary prevention.


Subject(s)
Cardiovascular System , Coronary Artery Disease , Diabetes Mellitus, Type 2 , Myocardial Infarction , Humans , Colchicine/therapeutic use , Colchicine/adverse effects , Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/drug therapy , Diabetes Mellitus, Type 2/chemically induced , Myocardial Infarction/drug therapy , Myocardial Infarction/prevention & control , Coronary Artery Disease/drug therapy
13.
Ann Intern Med ; 177(1): JC3, 2024 01.
Article in English | MEDLINE | ID: mdl-38163371

ABSTRACT

SOURCE CITATION: Conen D, Ke Wang M, Popova E, et al; COP-AF Investigators. Effect of colchicine on perioperative atrial fibrillation and myocardial injury after non-cardiac surgery in patients undergoing major thoracic surgery (COP-AF): an international randomised trial. Lancet. 2023;402:1627-1635. 37640035.


Subject(s)
Atrial Fibrillation , Thoracic Surgery , Humans , Colchicine/adverse effects , Postoperative Complications/prevention & control , Atrial Fibrillation/drug therapy , Atrial Fibrillation/etiology , Atrial Fibrillation/prevention & control
14.
Open Heart ; 11(1)2024 Jan 17.
Article in English | MEDLINE | ID: mdl-38233042

ABSTRACT

OBJECTIVE: In the COVERT-MI randomised placebo-controlled trial, oral administration of high-dose colchicine at the time of reperfusion and for 5 days in acute ST-elevated myocardial infarction did not reduce infarct size but was associated with a significant increase in left ventricular thrombus (LVT) in comparison to placebo. We aimed to assess the 1-year clinical outcomes of the study population. METHODS: This study is a follow-up analysis of the COVERT-MI study on prespecified secondary clinical endpoints at 1 year. The primary endpoint of this study was a composite of major adverse cardiovascular events (MACEs), including all-cause death, acute coronary syndromes, heart failure events, ischaemic strokes, sustained ventricular arrhythmias and acute kidney injury at 1-year follow-up. The quality of life (QOL) and the drug therapy prescription were also assessed. RESULTS: At 1 year, 192 patients (101 patients in the colchicine group, 91 in the placebo group) were followed up. Seventy-six (39.6%) MACEs were reported in the study population. There was no significant difference regarding the number of MACEs between groups: 36 (35.6%) in the colchicine group and 40 (44.1%) in the placebo group (p=0.3). There were no differences in the occurrence of ischaemic strokes between the colchicine group and the control group (3 (3%) vs 2 (2.2%), respectively, p=0.99). There was a trend towards fewer heart failure events in the colchicine group compared with the placebo group (12 (11.9%) vs 18 (19.8%), p=0.20). There was no significant difference in QOL scores at 1 year (75.8±15.7 vs 72.7±16.2 respectively, p=0.18). CONCLUSIONS: There was no significant difference between the colchicine and placebo groups at 1 year regarding MACEs, especially concerning deaths or ischaemic strokes. No excess of ischaemic adverse events was observed despite the initial increase in LVT in the colchicine group. TRIAL REGISTRATION NUMBER: NCT0315681.


Subject(s)
Heart Failure , Ischemic Stroke , Myocardial Infarction , Humans , Colchicine/adverse effects , Follow-Up Studies , Quality of Life , Myocardial Infarction/diagnosis , Myocardial Infarction/drug therapy
16.
RMD Open ; 10(1)2024 Jan 31.
Article in English | MEDLINE | ID: mdl-38296804

ABSTRACT

INTRODUCTION: Colchicine, commonly used in gout flare, is contraindicated in severe chronic kidney disease (CKD) (estimated glomerular filtration rate <30 mL/min). However, in this context, there are few alternatives, and colchicine use persists. We evaluated the tolerance of colchicine and its efficacy in patients with severe CKD. PATIENTS AND METHODS: All prescriptions of colchicine for managing crystal-induced arthritis flare (gout or calcium pyrophosphate deposition (CPPD) disease) in a hospitalised patient with severe CKD were screened from September 2020 to September 2021. After patient consent and treatment information, clinical and biological safety and efficacy data were prospectively collected from day 1 (D1) to D11. RESULTS: We included 54 patients (median age 75 years (IQR 67-83)) with 62 colchicine prescriptions (cases). Twelve (22%) patients were on dialysis. The main reason for hospitalisation was heart failure (31.5%), acute renal failure (22.2%), infection (18.5%) or an acute joint episode (9.3%). In total, 59.3% of patients had diabetes. The prescriptions concerned 58 cases of gout flares, 1 case of CPPD and 3 cases of both. Initial colchicine dosages were ≤0.5 mg/day in 47/62 (75.8%) cases; no dosage exceeded 1 mg/day (median duration of 6 days (IQR 3-11)). Colchicine was well tolerated in 47/61 (77%) cases. No serious adverse event was reported. Colchicine was considered completely effective by the medical team in 48/58 (83%) of cases. CONCLUSION: The use of colchicine, at reduced doses, was mostly effective to treat crystal-induced arthritis flare in 54 patients with severe CKD and was well tolerated, without any serious adverse events.


Subject(s)
Chondrocalcinosis , Gout , Renal Insufficiency, Chronic , Humans , Aged , Colchicine/adverse effects , Gout/complications , Gout/drug therapy , Symptom Flare Up , Chondrocalcinosis/chemically induced , Chondrocalcinosis/drug therapy , Renal Insufficiency, Chronic/complications , Renal Insufficiency, Chronic/drug therapy
17.
Food Funct ; 15(3): 1671-1688, 2024 Feb 05.
Article in English | MEDLINE | ID: mdl-38251779

ABSTRACT

Gout flares have emerged as a significant public health concern. Colchicine (COL) is a first-line and standard drug for treating gout flares. However, its clinical use is limited due to various adverse effects. Besides, COL fails to adequately meet the needs of patients, particularly young patients. In this study, we investigate the therapeutic administration of Lactobacillus paracasei GY-1 (GY-1) to overcome the limitations of COL. Our results demonstrate that GY-1 attenuates COL toxicity in terms of body weight loss, decreased feed intake, mortality, reduced locomotor activity, colon shortening, increased oxidative stress, histological damage, and impaired gut permeability. Meanwhile, we demonstrate that GY-1 enhances the therapeutic effect for gout flares when combined with COL, as evidenced by the reduction in paw swelling, decreased levels of proinflammatory cytokines including IL-1ß and TNF-α, and an increase in the anti-inflammatory cytokine IL-10. Additionally, the absolute quantification of the gut microbiota shows that GY-1 restores the gut microbiota imbalance caused by COL. Furthermore, GY-1 reduces the abundance of 4 Alistipes species and 6 Porphyromonadaceae species, which may be responsible for toxicity alleviation. At the same time, GY-1 increases the abundance of Bacteroides sartorii and Enterococcus sp., which may contribute to its therapeutic efficacy. This study demonstrates the feasibility of developing probiotic-based adjuvant therapy or bacteriotherapy for treating gout flares. To our knowledge, GY-1 is the first probiotic that could be used as an alternative synergetic agent with COL for the therapeutic treatment of gout flares.


Subject(s)
Gout , Lacticaseibacillus paracasei , Humans , Gout/drug therapy , Colchicine/adverse effects , Symptom Flare Up , Gout Suppressants , Cytokines
18.
J Cardiovasc Pharmacol ; 83(3): 265-270, 2024 Mar 01.
Article in English | MEDLINE | ID: mdl-38181213

ABSTRACT

ABSTRACT: The role of colchicine for the prevention of postoperative atrial fibrillation (POAF) after cardiothoracic surgery is not well-established. We aimed to evaluate its potential in preventing POAF using data from randomized controlled trials (RCTs). A literature search was performed to identify studies reporting POAF as an outcome after cardiac or thoracic surgery in adult patients randomized to either colchicine or placebo. Primary outcome measured was incidence of POAF. Secondary outcomes included gastrointestinal (GI) adverse effects, sepsis, and length of stay. Subgroup analyses based on treatment durations and type of surgery were also performed, as well as regression analyses to control for covariates. We identified a total of 5377 patients (colchicine = 2,689, placebo = 2688). Although colchicine use was associated with a significantly reduced risk of POAF, risk of GI adverse effects were significantly higher. The rates of infection and length of stay were similar across the groups. Subgroup analyses showed that colchicine was effective for POAF prevention in cardiac surgery, but not in thoracic surgery. Prevention of POAF and incidence of GI adverse effects were similar in short-term and long-term colchicine treatment. Colchicine significantly reduces the incidence of POAF in patients undergoing cardiac surgery, but not in thoracic surgery.


Subject(s)
Atrial Fibrillation , Cardiac Surgical Procedures , Adult , Humans , Atrial Fibrillation/diagnosis , Atrial Fibrillation/epidemiology , Atrial Fibrillation/etiology , Colchicine/adverse effects , Postoperative Complications/epidemiology , Postoperative Complications/prevention & control , Randomized Controlled Trials as Topic , Cardiac Surgical Procedures/adverse effects
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