Cost-effectiveness of low-dose colchicine in patients with chronic coronary disease in the netherlands.

AIMS: Recent trials have shown that low-dose colchicine (0.5 mg once daily) reduces major cardiovascular events in patients with acute and chronic coronary syndromes. We aimed to estimate the cost-effectiveness of low-dose colchicine therapy in patients with chronic coronary disease when added to standard background therapy. METHODS AND RESULTS: This Markov cohort cost-effectiveness model used estimates of therapy effectiveness, transition probabilities, costs and quality of life obtained from the Low-dose Colchicine 2 (LoDoCo2) trial, as well as meta-analyses and public sources. In this trial, Low-dose colchicine was added to standard of care and compared to placebo. The main outcomes were cardiovascular events including myocardial infarction, stroke and coronary revascularisation, quality-adjusted life-year (QALY), the cost per QALY gained (incremental cost-effectiveness ratio), and net monetary benefit. In the model, low-dose colchicine therapy yielded 0.04 additional QALYs compared with standard of care at an incremental cost of €455 from a societal perspective and €729 from a healthcare perspective, resulting in a cost per QALY gained of €12,176/QALY from a societal perspective and €19,499/QALY from a healthcare perspective. Net monetary benefit was €1,414 from a societal perspective and €1,140 from a healthcare perspective. Low-dose colchicine has a 96% and 94% chance of being cost effective, from respectively a societal and healthcare perspective when using a willingness to pay of €50,000/QALY. Net monetary benefit would decrease below zero when annual low-dose colchicine costs would exceed an annual cost of €221 per patient. CONCLUSION: Adding low-dose colchicine to standard of care in patients with chronic coronary disease is cost-effective according to commonly accepted thresholds in Europe and Australia and compares favourably in cost-effectiveness to other drugs used in chronic coronary disease.

Colchicine: an affordable anti-inflammatory agent for atherosclerosis.

PURPOSE OF REVIEW: Inflammation has been shown to be central to the development and progression of atherosclerosis. Despite detailed understanding of its central role and the cellular dynamics, which contribute to atherosclerotic inflammation, there has been slow progress in finding suitable agents to treat it. The recent CANTOS trial showed that the interleukin-1ß inhibitor canakinumab can improve outcomes after acute coronary syndromes. Being a monoclonal antibody, it is expensive and inconvenient to administer for long-term treatment. This review summarizes recent work in finding effective, affordable alternatives to canakinumab. RECENT FINDINGS: Statin drugs have anti-inflammatory properties but separating their LDL lowering effect from their anti-inflammatory effect has been difficult. Drugs acting on targets outside of the interleukin-1ß (IL-1ß) pathway have been tested without finding a suitable candidate. Following the proof of principle provided by the success of canakinumab, other candidates targeting the IL-1ß pathway are undergoing detailed evaluation. The most likely candidates are low-dose methotrexate and low-dose colchicine. The potential mechanisms and ongoing clinical trials are described. SUMMARY: Targeting the IL-1ß pathway has already been successful with canakinumab but its expense and inconvenience of administration may limit its widespread uptake for controlling inflammation in atherosclerosis. Low-dose methotrexate and low-dose colchicine are affordable and more accessible alternatives, currently undergoing detailed evaluation for safety and efficacy in large randomized controlled trials.

Targeting the unstable plaque in acute coronary syndromes.

BACKGROUND: Rupture or erosion of an unstable atherosclerotic plaque is the typical pathology and usual cause of acute coronary syndromes. Despite detailed understanding of the processes of lipid accumulation, thinning of the fibrous cap, and inflammation leading to plaque instability, there are no strategies in clinical use that uniquely target the unstable plaque. OBJECTIVE: A critical review of recent publications on potential therapies that could be used to stabilize unstable plaque. METHODS: We searched PubMed, other literature databases, drug development sites, and clinical trial registries to retrieve clinical studies on anti-inflammatory and lipid-modulating therapies that could be used to stabilize unstable atherosclerotic plaque. RESULTS: Multiple experimental targets involving lipid and inflammatory pathways have the potential to stabilize the plaque and expand the armamentarium against coronary artery disease. Randomized clinical trials of darapladib, methotrexate, canakinumab, and colchicine are well advanced to establish if plaque stabilization is feasible and effective in patients with acute coronary syndromes. CONCLUSIONS: Although there are still no agents in clinical use for plaque stabilization, there are important advances in understanding plaque instability and several encouraging approaches are being evaluated in Phase III clinical trials.