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25th January 2022
Colchicine use in patients with coronary artery disease undergoing a percutaneous intervention, significantly reduced the incidence of major adverse cardiovascular events (MACE) according to a meta-analysis by a team from the University of Oxford, UK.
Coronary artery disease is characterised by atherosclerotic plaque accumulation in the epicardial arteries and can be managed with various interventions including lifestyle modification, pharmacological therapies and invasive interventions, all of which are designed to achieve disease stabilisation or regression. One particular intervention is percutaneous coronary intervention (PCI) and defined as a non-surgical, invasive procedure which seeks to relieve the narrowing or occlusion of the coronary artery and improve blood supply to the ischaemic tissue.
The importance of inflammation in the pathogenesis of coronary artery disease was established many years ago and during PCI, damage to the endothelial layer after stent implantation can also lead to a further inflammatory response. Moreover, the presence of residual inflammation can increase the risk of subsequent complications such as a myocardial infarction therefore highlighting the importance of minimising inflammation to improve patient outcomes.
Colchicine use represents a low cost anti-inflammatory agent and there is evidence that they drug has beneficial effects as a secondary preventative measure, especially after a myocardial infarction. Nevertheless, the value of colchicine use as an adjunctive intervention to PCI to prevent cardiovascular events remains unclear and was the objective of the current analysis.
The team undertook a systematic review and meta-analysis for studies that compared the efficacy of colchicine use to either no use or placebo in patients undergoing PCI and which reported on MACE. The primary outcome measures were the MACE and which included outcomes including in-stent restenosis (ISR), repeat vessel revascularisation, stent thrombosis, stroke and all cause mortality.
A total of 7 trials including 6660 participants with a mean age of 60.9 years (3347 assigned to colchicine use) and a follow-up time ranging from 3 days to 22.6 months were analysed.
The incidence of MACE was 7.08% in those assigned to colchicine use and 9.15% in the control arm, leading to a significant reduction in MACE (risk ratio, RR = 0.73, 95% CI 0.61 – 0.87, p = 0.0003) and with little evidence of heterogeneity across the analysis.
Use of colchicine was associated with a significant reduction in stent thrombosis (RR = 0.50), repeat vessel revascularisation (RR = 0.47) and stroke (RR = 0.50). However, there was no significant difference in all-cause mortality (RR = 1.12, 95% CI 0.49 – 2.58, p = 0.79).
The authors calculated the number needed to treat with colchicine to prevent one episode of MACE to be 41. They concluded that colchicine use significantly reduced the risk of MACE in patients with coronary artery disease undergoing PCI and called for future trials to further evaluate the value of colchicine with different types of stents and alternative dosing regimes.
Aw KL et al. Colchicine for symptomatic coronary artery disease after percutaneous coronary intervention Open Heart 2022
28th May 2021
Infection with COVID-19 has been found to be associated with raised levels of systemic inflammatory markers such as C-reactive protein (CRP), interleukin-6 (IL-6) and other cytokines. In addition, data have revealed how engagement of protein platforms (inflammasomes) and in particular, the nucleotide binding domain-like pyrin domain 3 (NLRP3) inflammasome, is strongly associated with disease severity.
The anti-inflammatory gout drug, colchicine, is known to inhibit the NLRP3 inflammasome and may therefore be of value in the treatment of patients hospitalised with COVID-19. The randomised evaluation of COVID-19 therapy (RECOVERY) trial aims to evaluate a number of therapeutic options for the management of hospitalised patients infected with COVID-19. The RECOVERY group have investigated several different treatments and recently examined the use of colchicine. For the present trial, patients were randomised 1:1 to usual care or usual care plus colchicine at a dose of 1mg after randomisation, followed by 500mcg 12 hours later and then 500mcg twice daily (orally or via nasogastric tube) for 10 days or until discharged from hospital. However, although patients were randomised, this was an open label trial, hence both treating clinicians and patients were not masked to treatment allocation although the study steering group and investigated were masked to outcome data during the trial. The primary outcome was all-cause mortality and assessed at 28 days post-randomisation. Secondary outcomes included time to hospital discharge and the need for invasive mechanical ventilation.
A total of 5610 patients with a mean age of 63.4 years (31% female) and of predominately (77%) White ethnicity, were randomised to colchicine and 5730 to usual care. The median duration of treatment with colchicine was 6 days and use of all other treatments was similar between the two groups. The proportion of patients allocated to colchicine who achieved the primary outcome was not different to placebo (21%) and the median time to hospital discharge was 10 days and again, similar between the two groups. Moreover, an equal number of patients progressed to invasive mechanical ventilation (70%).
In discussing these findings, the authors commented on how the use of colchicine had no impact on mortality, duration of hospitalisation or the need for mechanical ventilation. Additionally, this effect was evidence across all ages, ethnic groups and irrespective of symptom duration prior to randomisation. They also speculated that the anti-inflammatory properties of colchicine were either inadequate or did not sufficiently target the pathways induced by COVID-19 and concluded that the drug was of no benefit to those hospitalised with COVID-19.
RECOVERY Collaborative Group. Colchicine in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial. MedRxiv 2021