The effect of low-dose colchicine in patients with stable coronary artery disease: The LoDoCo2 trial rationale, design, and baseline characteristics.

Because patients with stable coronary artery disease are at continued risk of major atherosclerotic events despite effective secondary prevention strategies, there is a need to continue to develop additional safe, effective and well-tolerated therapies for secondary prevention of cardiovascular disease. RATIONALE AND DESIGN: The LoDoCo (Low Dose Colchicine) pilot trial showed that the anti-inflammatory drug colchicine 0.5 mg once daily appears safe and effective for secondary prevention of cardiovascular disease. Colchicine's low cost and long-term safety suggest that if its efficacy can be confirmed in a rigorous trial, repurposing it for secondary prevention of cardiovascular disease would have the potential to impact the global burden of cardiovascular disease. LoDoCo2 is an investigator-initiated, international, multicentre, double-blind, event driven trial in which 5522 patients with stable coronary artery disease tolerant to colchicine during a 30-day run-in phase have been randomized to colchicine 0.5 mg daily or matching placebo on a background of optimal medical therapy. The study will have 90% power to detect a 30% reduction in the composite primary endpoint: cardiovascular death, myocardial infarction, ischemic stroke and ischemia-driven coronary revascularization. Adverse events potentially related to the use of colchicine will also be collected, including late gastrointestinal intolerance, neuropathy, myopathy, myositis, and neutropenia. CONCLUSION: The LoDoCo2 Trial will provide information on the efficacy and safety of low-dose colchicine for secondary prevention in patients with stable coronary artery disease.

Nidorf SM ，Fiolet ATL ，Eikelboom JW ，Schut A ，Opstal TSJ ，Bax WA ，Budgeon CA ，Tijssen JGP ，Mosterd A ，Cornel JH ，Thompson PL ，LoDoCo2 Investigators ... -  《-》

[Colchicine in patients with coronary heart disease : LoDoCo2 trial].

Koenig W ，Nitschmann S 《-》

Colchicine in Patients With Chronic Coronary Disease in Relation to Prior Acute Coronary Syndrome.

Colchicine reduces risk of cardiovascular events in patients post-myocardial infarction and in patients with chronic coronary disease. It remains unclear whether this effect is related to the time of onset of treatment following an acute coronary syndrome (ACS). This study investigates risk for major adverse cardiovascular events in relation to history and timing of prior ACS, to determine whether the benefits of colchicine are consistent independent of prior ACS status. The LoDoCo2 (Low-Dose Colchicine 2) trial randomly allocated patients with chronic coronary disease to colchicine 0.5 mg once daily or placebo. The rate of the composite of cardiovascular death, spontaneous myocardial infarction, ischemic stroke, or ischemia-driven coronary revascularization was compared between patients with no prior, recent (6-24 months), remote (2-7 years), or very remote (>7 years) ACS; interaction between ACS status and colchicine treatment effect was assessed. In 5,522 randomized patients, risk of the primary endpoint was independent of prior ACS status. Colchicine consistently reduced the primary endpoint in patients with no prior ACS (incidence: 2.8 vs 3.4 events per 100 person-years; hazard ratio [HR]: 0.81; 95% confidence interval [CI]: 0.52-1.27), recent ACS (incidence: 2.4 vs 3.3 events per 100 person-years; HR: 0.75; 95% CI: 0.51-1.10), remote ACS (incidence: 1.8 vs 3.2 events per 100 person-years, HR: 0.55; 95% CI: 0.37-0.82), and very remote ACS (incidence: 3.0 vs 4.3 events per 100 person-years, HR: 0.70; 95% CI: 0.51-0.96) (P for interaction = 0.59). The benefits of colchicine are consistent irrespective of history and timing of prior ACS. (The LoDoCo2 Trial: Low Dose Colchicine for secondary prevention of cardiovascular disease [LoDoCo2] ACTRN12614000093684).

Opstal TSJ ，Fiolet ATL ，van Broekhoven A ，Mosterd A ，Eikelboom JW ，Nidorf SM ，Thompson PL ，Duyvendak M ，van Eck JWM ，van Beek EA ，den Hartog F ，Budgeon CA ，Bax WA ，Tijssen JGP ，El Messaoudi S ，Cornel JH ，LoDoCo2 Trial Investigators ... -  《-》

Low-dose colchicine for the prevention of cardiovascular events after percutaneous coronary intervention: Rationale and design of the COL BE PCI trial.

Patients with coronary artery disease (CAD) remain vulnerable to future major atherosclerotic events after revascularization, despite effective secondary prevention strategies. Inflammation plays a central role in the pathogenesis of CAD and recurrent events. To date, there is no specific anti-inflammatory medicine available with proven effective, cost-efficient, and favorable benefit-risk profile, except for colchicine. Initial studies with colchicine have sparked major interest in targeting atherosclerotic events with anti-inflammatory agents, but further studies are warranted to enforce the role of colchicine role as a major treatment pillar in CAD. Given colchicine's low cost and established acceptable long-term safety profile, confirming its efficacy through a pragmatic trial holds the potential to significantly impact the global burden of cardiovascular disease. The COL BE PCI trial is an investigator-initiated, multicenter, double-blind, event-driven trial. It will enroll 2,770 patients with chronic or acute CAD treated with percutaneous coronary intervention (PCI) at 19 sites in Belgium, applying lenient in- and exclusion criteria and including at least 30% female participants. Patients will be randomized between 2 hours and 5 days post-PCI to receive either colchicine 0.5 mg daily or placebo on top of contemporary optimal medical therapy and without run-in period. All patients will have baseline hsCRP measurements and a Second Manifestations of Arterial Disease (SMART) risk score calculation. The primary endpoint is the time from randomization to the first occurrence of a composite endpoint consisting of all-cause death, spontaneous non-fatal myocardial infarction, non-fatal stroke, or coronary revascularization. The trial is event-driven and will continue until 566 events have been reached, providing 80% power to detect a 21 % reduction in the primary endpoint taking a premature discontinuation of 15% into account. We expect a trial duration of approximately 44 months. The COL BE PCI Trial aims to assess the effectiveness and safety of administering low-dose colchicine for the secondary prevention in patients with both chronic and acute coronary artery disease undergoing PCI. ClinicalTrials.gov: NCT06095765.

De Cock E ，Kautbally S ，Timmermans F ，Bogaerts K ，Hanet C ，Desmet W ，Gurné O ，Vranckx P ，Hiltrop N ，Dujardin K ，Vanduynhoven P ，Vermeersch P ，Pirlet C ，Hermans K ，Van Reet B ，Ferdinande B ，Aminian A ，Dewilde W ，Guédès A ，Simon F ，De Roeck F ，De Vroey F ，Jukema JW ，Sinnaeve P ，Buysschaert I ... -  《-》

Seeing Colchicine in a New Light: Repurposing Low-dose Colchicine for Secondary Prevention of Cardiovascular Disease.

This review presents a modern perspective on the cardiovascular re-purposing of colchicine, the oldest drug in the pharmacopeia other than aspirin that is still in regular use. This article presents a brief overview of colchicine's long history as a medicine, as well as a critical review of safety and efficacy from the results of recent cardiovascular clinical trials. Long-term continuous colchicine use at doses between 0.6 and 2.4 mg has been used to prevent inflammatory flares in patients with gout and familial Mediterranean fever and less commonly employed in a range of other inflammatory conditions. In these settings, lifelong therapy has been found to be safe and well tolerated. Understanding the central role of inflammation in atherosclerosis has led to the search for effective anti-inflammatory agents that can be used continuously in combination with a range of other medications, including lipid-lowering therapies, antiplatelet therapy, and anticoagulants. The results of recent robust randomized clinical trials of low-dose colchicine (0.5 mg daily) in patients with coronary disease recently led the US Food and Drug Administration to approve its use as a new cornerstone therapy for secondary prevention in patients with coronary disease. Several misconceptions regarding the safety and tolerability of low dose colchicine are addressed. Colchicine has emerged from its traditional role in medicine as the prevention of gout flare as the first anti-inflammatory agent to be approved by the US Food and Drug Administration for the secondary prevention of atherosclerosis.

Nidorf SM 《-》