Efficacy Of Colchicine In Patients Research Articles

Colchicine and diabetes in patients with chronic coronary artery disease: insights from the LoDoCo2 randomized controlled trial.

Despite optimal treatment, patients with chronic coronary artery disease (CAD) and diabetes mellitus (DM) are at high risk of cardiovascular events, emphasizing the need for new treatment options. The Low-Dose Colchicine 2 (LoDoCo2) trial demonstrated that colchicine reduces cardiovascular risk in patients with chronic CAD. This analysis determines the efficacy of colchicine in patients with chronic CAD and DM as well as the effect of colchicine on the development of new-onset type 2 diabetes mellitus (T2DM). The LoDoCo2 trial randomized 5,522 patients to placebo or colchicine 0.5 mg once daily, with a median follow-up of 28.6 months. The primary composite endpoint was cardiovascular death, spontaneous myocardial infarction, ischemic stroke, or ischemia-driven revascularization. The effect of its treatment in patients with and without DM was evaluated by including an interaction term in the model. A total of 1,007 participants (18.2%) had T2DM at baseline. The adjusted hazard ratio (HR) [(95% confidence interval (CI)] for the primary endpoint in the T2DM group was 1.52 (1.15-2.01, p < 0.01) compared with the group without T2DM. The HR for the treatment effect on the primary endpoint was 0.87 (0.61-1.25) in participants with T2DM and 0.64 (0.51-0.80) in participants without diabetes (pinteraction = 0.14). The incidence of new-onset T2DM was 1.5% (34 out of 2,270) in the colchicine group and 2.2% (49 out of 2,245) in the placebo group (p = 0.10). In conclusion, based on the current evidence, the beneficial effects of colchicine on cardiovascular endpoints are consistent regardless of DM status. The potential benefits of colchicine in preventing new-onset DM need further investigation. These findings are only hypothesis-generating and require larger prospective trials to confirm the results.

Colchicine for cardiovascular medicine: a systematic review and meta-analysis.

Aim: Colchicine, a microtubule-disassembling (antitubulin) agent used for centuries for the treatment of gout and autoimmune diseases, is a drug of growing interest in the cardiovascular field. While in the last decades it has become cornerstone of pericarditis treatment, it has also emerged in the last few years as a promising drug in the management of coronary artery disease, atrial fibrillation and heart failure. This systematic review and meta-analysis aimed to assess the efficacy of colchicine in patients with cardiovascular diseases. Methods: Systematic search in electronic databases (MEDLINE/PubMed, Scopus, BioMed Central, the Cochrane Collaboration Database of Randomized Trials, ClinicalTrials.gov, EMBASE, Google Scholar) was performed to identify randomized controlled trials (RCTs) up to February 2021. Random-effects meta-analysis was performed to assess the risk of cardiovascular events, defined according to clinical setting. Results: Among 15,569 pooled patients from 21 RCTs, colchicine was superior to placebo in the reduction of cardiovascular events. In the setting of pericardial diseases, it was associated with a lower risk of recurrent pericarditis (17 vs 34%, RR=0.50, 95% CI: 0.42-0.60, I2=10%). In other studies assessing coronary artery disease patients, colchicine was associated with a reduced risk of major adverse cardiovascular events (MACE) such as myocardial infarction, stroke, cardiovascular death, coronary revascularisation and hospitalization (6.3 vs 9%, RR=0.67, 95% CI: 0.54-0.84, I2=55). Among patients with atrial fibrillation, it was associated with lower rates of recurrence (20 vs 30%, RR=0.68, 95% CI: 0.58-0.81, I2=0). In the single RCT on heart failure, colchicine was not associated with improved NYHA class. Conclusion: Colchicine is a valuable anti-inflammatory agent for the prevention of cardiovascular events in patients with inflammatory cardiac conditions such as pericardial diseases, coronary artery disease and atrial fibrillation.

Canakinumab is effective in patients with familial Mediterranean fever resistant and intolerant to the colchicine and/or anakinra treatment.

As an autosomal recessive autoinflammatory disease, treatment of Familial Mediterranean fever (FMF) has still gaps. Clinical studies are proving the safety and efficacy of colchicine in patients with FMF. However, there are very limited data on colchicine-resistant patients treated with canakinumab. This study presents the real-life experience of two rheumatology clinics choosing canakinumab in adult patients with FMF resistant to standard therapy. Treatment-resistant FMF patients with validated diagnoses enrolled from two rheumatology clinics. A special database was generated for the study and patients' demographic characteristics, FMF attack characteristics, adverse events seen during treatment, family history, MediterraneanFeVer (MEFV) mutations, and laboratory results recorded. Patients with missing dates were excluded from the analysis. PRAS score is used to assess the disease activity. A total of thirty colchicine and/or anakinra-resistant patients were enrolled to study. Twenty-one patients were female (70%) and the average disease duration was 21years. The time from colchicine to anakinra was 4.27years and the time to canakinumab was 1.52years. Abdominal pain (100%), fever (93.3%), chest pain (56.7%) were the most prevailed findings. Morning stiffness, myalgia, low back pain, chest pain was the predominant musculoskeletal findings. Median colchicine dose was 2mg/day (min-max 0.5-3mg/day). The most common side effect during anakinra treatment, apart from treatment unresponsiveness, was injection site reactions. Before canakinumab treatment, the mean number of attacks was 8.3 in the 24weeks, 4.33 in the third month of canakinumab treatment, and 1.56 at the last visit (p < 0.001). Also, the mean duration of attacks was 67.20h before canakinumab treatment, this period decreased to 18.27h after six months of canakinumab treatment (p < 0.001). Canakinumab is effective and tolerable to reduce attacks in resistant patients with FMF. Laboratory findings and clinical observation reveals that canakinumab can be another treatment option for colchicine and/or anakinra non-responders. Further studies with larger patients are required to validate recent findings with canakinumab.

Safety and Efficacy of Colchicine in Patients with Stable CAD and ACS: A Systematic Review and Meta-analysis.

Evidence from recent trials has shown conflicting results in terms of the utility of colchicine in patients with coronary artery disease (CAD). Multiple databases were queried to identify all randomized controlled trials (RCTs) comparing the merits of colchicine in patients with acute coronary syndrome (ACS) or stable CAD. The pooled relative risk ratio (RR) of major adverse cardiovascular events (MACE), its components, and gastrointestinal (GI) adverse events were computed using a random-effect model. Ten RCTs comprising a total of 12,761 patients were identified. At a median follow-up of 12 months, there was a significantly lower risk of MACE [RR 0.66, 95% confidence interval (CI) 0.45-96], ACS (RR 0.66, 95% CI 0.45-0.96), ischemic stroke (RR 0.42, 95% CI 0.22-0.81), and need for revascularization (RR 0.61, 95% CI 0.42-90) in patients receiving colchicine compared with placebo. A subgroup analysis based on the clinical presentation showed that the significantly lower incidence of MACE and stroke were driven by the patients presenting with ACS. The use of colchicine in patients with stable CAD did not reduce the incidence of MACE (RR 0.55, 95% CI 0.28-1.09), ACS (RR 0.52, 95% CI 0.25-1.08), or stroke (RR 0.61, 95% CI 0.33-1.13). There was no significant difference in the relative risk of cardiac arrest, ACS, cardiovascular mortality, and all-cause mortality between the two groups in both ACS and stable CAD populations. The risk of GI adverse events was significantly higher in patients receiving colchicine (RR 2.10, 95% CI 1.12-3.95). In patients presenting with ACS, low-dose colchicine might reduce the incidence of MACE, stroke, and the need for revascularization at long follow-up durations. Colchicine might offer no benefits in reducing the risk of ischemic events in patients with stable angina.

Safety and Efficacy of Colchicine in Patients With Coronary Artery Disease: A Systematic Review and Meta-Analysis

BackgroundGiven current evidence, the use of colchicine for the prevention of adverse cardiovascular events in patients with coronary artery disease (CAD) remains controversial. MethodsMultiple databases were queried to identify studies comparing the safety and efficacy of colchicine in patients with acute coronary syndrome (ACS) or stable angina. The relative risk (RR) of major adverse cardiovascular events (MACE) and gastrointestinal (GI) adverse events were calculated using a random-effect model. ResultsSix clinical trials comprising a total of 5820 patients were identified. The pooled RR of MACE (0.64, 95% confidence interval (CI) 0.36–1.14, p = 0.13), ACS (0.62, 95% CI 0.27–1.41, p = 0.25), cardiac arrest (0.74, 95% CI 0.26–2.14, p = 0.58), stent restenosis (0.71, 95% CI 0.41–1.23, p = 0.22) and mortality (0.95, 95% CI 0.63–1.42, p = 0.79) with colchicine was not significantly different from placebo or control groups. The overall RR of revascularization (0.53, 95% CI 0.34–0.83, p = 0.005) and stroke (0.26, 95% CI 0.11–0.62, p = 0.002) was significantly lower while the net RR of GI adverse events was significantly higher (HR 2.66, 95% CI 1.21–5.87, p = 0.02) in the colchicine group. Propensity matched cohort, sensitivity and subgroup analysis based on adjusted MACE and dosages of colchicine all mirrored the overall results. ConclusionIn patients with CAD presenting with an acute coronary syndrome or stable angina, colchicine might offer no significant reduction in MACE and could potentially be harmful due to a significantly higher risk of GI-related adverse events.

Colchicina administrada en el primer episodio de pericarditis aguda idiopática: estudio multicéntrico abierto y aleatorizado

Introduction and objectivesThere is a paucity of information about the real benefit of colchicine administration in the first episode of acute idiopathic pericarditis (AIP). The main objective of the present study was to assess the real efficacy of colchicine in patients with AIP who did not receive corticosteroids. MethodsRandomized multicenter open-label study. Patients with a first episode of AIP (not secondary to cardiac injury or connective tissue disease) were randomized into 2 groups: group A received conventional anti-inflammatory treatment plus colchicine for 3 months, and group B received conventional anti-inflammatory treatment only. None of the patients received corticosteroids. The primary endpoint was the appearance of recurrent episodes of pericarditis. The secondary endpoint was the time to first recurrence. Follow-up was extended to 24 months. ResultsA total of 110 patients (83.6% men, age 44±18.3 years) were randomized to group A (n=59) and group B (n=51). No differences were found in baseline demographics or in the clinical features of the index episode or in the type of anti-inflammatory treatment administered in both groups. The follow-up was completed by 102 patients (92.7%). No differences were found in the rate of recurrent pericarditis between groups (12 patients [10.9%]; group A vs group B, 13.5% vs 7.8%; P=.34). The time to first recurrence (group A vs group B, 9.6±9.0 vs 8.3±10.5 months; P=.80) did not differ between groups. ConclusionsAmong patients with a first episode of AIP who had not received corticosteroids, the addition of colchicine to conventional anti-inflammatory treatment does not seem to reduce the recurrence rate. Clinical trial registration: URL: https://www.clinicaltrialsregister.eu. Identifier: EudraCT 2009-011258-16.Full English text available from:www.revespcardiol.org/en

Colchicine Administered in the First Episode of Acute Idiopathic Pericarditis: A Randomized Multicenter Open-label Study.

There is a paucity of information about the real benefit of colchicine administration in the first episode of acute idiopathic pericarditis (AIP). The main objective of the present study was to assess the real efficacy of colchicine in patients with AIP who did not receive corticosteroids. Randomized multicenter open-label study. Patients with a first episode of AIP (not secondary to cardiac injury or connective tissue disease) were randomized into 2 groups: group A received conventional anti-inflammatory treatment plus colchicine for 3 months, and groupB received conventional anti-inflammatory treatment only. None of the patients received corticosteroids. The primary endpoint was the appearance of recurrent episodes of pericarditis. The secondary endpoint was the time to first recurrence. Follow-up was extended to 24 months. A total of 110 patients (83.6%men, age 44±18.3years) were randomized to groupA (n=59) and groupB (n=51). No differences were found in baseline demographics or in the clinical features of the index episode or in the type of anti-inflammatory treatment administered in both groups. The follow-up was completed by 102patients (92.7%). No differences were found in the rate of recurrent pericarditis between groups (12 patients [10.9%]; groupA vs group B, 13.5% vs 7.8%; P=.34). The time to first recurrence (groupA vs group B, 9.6±9.0 vs 8.3±10.5months; P=.80) did not differ between groups. Among patients with a first episode of AIP who had not received corticosteroids, the addition of colchicine to conventional anti-inflammatory treatment does not seem to reduce the recurrence rate. URL: https://www.clinicaltrialsregister.eu. Identifier: EudraCT 2009-011258-16.

Colchicine is effective for short-term treatment of slow transit constipation: a double-blind placebo-controlled clinical trial

Although colchicine has been tested in clinical trials for treatment of constipation, the index groups in those trials were composed of special patient groups with developmental neuromuscular defects or failed surgical management. The aim of this study is to investigate the efficacy of colchicine in patients with refractory slow transit constipation. Sixty patients with chief complaint of chronic constipation due to slow transit consented to be included in the double-blind placebo-controlled clinical trial. These patients were randomly divided into two groups (each containing 30 patients) to receive either colchicine, 1 mg QD, (group A) or placebo (group B) for 2 months. At the end of the study, Knowles-Eccersly-Scot symptom (KESS, a valid technique to assist in the diagnosis and evaluation of symptoms in constipation) scores were compared between the case and control groups. The mean KESS score measured at the end of 2 months was 11.67 +/- 3.91 for colchicine and 18.66 +/- 3.72 for placebo group (p = 0.0001). This trial shows that low-dose colchicine is effective in treatment of slow transit constipation.

Efficacy of colchicine in patients with primary biliary cirrhosis poorly responsive to ursodiol and methotrexate

Objective Approximately 20–30% of patients with primary biliary cirrhosis (PBC) respond fully to treatment with ursodeoxycholic acid (UDCA). The rest have progressive disease and eventually develop cirrhosis and liver failure. More effective treatment is needed. Methotrexate improved biochemical tests of liver function and liver histology in patients with PBC who had failed to respond to UDCA in one report and induced sustained biochemical and histological remission in another. The role of colchicine in PBC is unclear. We describe three patients with symptomatic PBC who responded very well to the addition of colchicine after they had failed to respond to UDCA alone and in combination with methotrexate. We suggest that colchicine should be tried in PBC patients who clearly fail to respond to UDCA. Methods Three patients with symptomatic biopsy-proven, antimitochondrial antibody-positive PBC failed to respond to UDCA and then to the addition of methotrexate. Colchicine was eventually added to the regimen. Symptoms, biochemical tests of liver function, and percutaneous liver biopsies were done at baseline, after treatment with UDCA, UDCA plus methotrexate, and UDCA plus methotrexate plus colchicine. Results All three patients responded after colchicine was added to UDCA and methotrexate. Symptoms, biochemical tests of liver function, and liver histology improved in all, and blood tests normalized in two. Conclusions Colchicine may be effective treatment in some symptomatic patients with PBC who respond incompletely to UDCA alone or in combination with methotrexate. Colchicine may be tried in such patients.