The COLchicine Cardiovascular Outcomes Trial (COLCOT) demonstrated the benefits of targeting inflammation after myocardial infarction (MI). We aimed to determine whether time-to-treatment initiation (TTI) influences the beneficial impact of colchicine. In COLCOT, patients were randomly assigned to receive colchicine or placebo within 30 days post-MI. Time-to-treatment initiation was defined as the length of time between the index MI and the initiation of study medication. The primary efficacy endpoint was a composite of cardiovascular death, resuscitated cardiac arrest, MI, stroke, or urgent hospitalization for angina requiring coronary revascularization. The relationship between endpoints and various TTI (<3, 4–7 and >8 days) was examined using multivariable Cox regression models. Amongst the 4661 patients included in this analysis, there were 1193, 720, and 2748 patients, respectively, in the three TTI strata. After a median follow-up of 22.7 months, there was a significant reduction in the incidence of the primary endpoint for patients in whom colchicine was initiated < Day 3 compared with placebo [hazard ratios (HR) = 0.52, 95% confidence intervals (CI) 0.32–0.84], in contrast to patients in whom colchicine was initiated between Days 4 and 7 (HR = 0.96, 95% CI 0.53–1.75) or > Day 8 (HR = 0.82, 95% CI 0.61–1.11). The beneficial effects of early initiation of colchicine were also demonstrated for urgent hospitalization for angina requiring revascularization (HR = 0.35), all coronary revascularization (HR = 0.63), and the composite of cardiovascular death, resuscitated cardiac arrest, MI, or stroke (HR = 0.55, all P < 0.05). Patients benefit from early, in-hospital initiation of colchicine after MI. COLCOT ClinicalTrials.gov number, NCT02551094.

Background and Aims: Immune checkpoint inhibitors (ICI) are associated with life-threatening myocarditis but milder presentations are increasingly recognized. The same autoimmune process that causes ICI myocarditis can manifest concurrent generalized myositis, myasthenia-like syndrome, and respiratory muscle failure. Prognostic factors for this ‘cardiomyotoxicity’ are lacking. The main aim of this study was to determine predictors and construct a risk score associated with negative outcomes in patients admitted for ICI myocarditis. Methods: A multicentre registry collected data retrospectively from 17 countries between 2014 and 2023. A multivariable Cox regression model was used to determine risk factors for the primary composite outcome: time to severe arrhythmia, heart failure, respiratory muscle failure, and/or cardiomyotoxicity-related death. Covariates included demographics, comorbidities, cardiomuscular symptoms, diagnostics, and treatments. Time-dependent covariates were used, and missing data were imputed. A point-based prognostic risk score was derived and externally validated. Results: In 748 patients (67% male, age 23–94 years), 30-day incidence of the primary composite outcome, cardiomyotoxic death, and overall death were 33%, 13%, and 17%, respectively. By multivariable analysis, the primary composite outcome was associated with active thymoma (hazard ratio [HR] 3.6, 95% confidence interval [CI] 1.7–7.7), presence of cardiomuscular symptoms (HR 2.6 [1.5–4.2]), low QRS voltage on presenting electrocardiogram (HR for ≤0.5 mV vs >1 mV 1.9 [1.1–3.1]), left ventricular ejection fraction (LVEF) < 50% (HR 1.7 [1.1–2.6]), and incremental troponin elevation (HR 1.8 [1.4–2.4], 2.9 [1.8–4.7], and 4.6 [2.3–9.3], for 20, 200, and 2000-fold above upper reference limit, respectively). A prognostic risk score developed using these parameters showed good performance; 30-day primary outcome incidence increased gradually from 4% (risk score = 0) to 81% (risk score ≥ 4). This risk score was externally validated in two independent French and US cohorts. This risk score was used prospectively in the external French cohort to identify low-risk patients who were managed with no immunosuppression resulting in no cardiomyotoxic events. Conclusions: ICI-associated myocarditis can manifest with high morbidity and mortality. Myocarditis severity is associated with magnitude of troponin, thymoma, low QRS voltage, depressed LVEF, and cardiomuscular symptoms. A risk score incorporating these features performed well. Clinical trial registration: NCT04294771 and NCT05454527.

Background and Aims: Colchicine has emerged as a safe and inexpensive anti-inflammatory medication to target the residual risk of cardiovascular events in the secondary prevention of coronary artery disease. Two recently published randomized controlled trials (RCTs) investigating colchicine in the post-stroke and post-myocardial infarction (MI) populations warrant a re-evaluation of colchicine. New evidence was synthesized in a systematic review and meta-analysis to determine the long-term efficacy and safety of colchicine for the secondary prevention of vascular disease. Methods: Randomized controlled trials comparing the incidence of cardiovascular events between patients with clinically manifest vascular disease randomized to colchicine vs. placebo and ≥12-month follow-up were included. The primary efficacy endpoint is major adverse cardiovascular events (MACE) and includes cardiovascular mortality, MI, ischaemic stroke, and urgent coronary revascularization. The DerSimonian and Laird random effects model was used to calculate pooled effect estimates. Results: Six RCTs, with a pooled sample size of 21 800 patients, were included (colchicine n = 10 871; placebo n = 10 929). Over a follow-up of 12–34 months, colchicine reduced the incidence of MACE compared with placebo [pooled hazard ratio .75, 95% confidence interval (CI) .56–.93]. The reduction in cardiovascular events among colchicine patients was driven by reductions in MIs, ischaemic strokes, and urgent coronary revascularizations (P < .05 for all). No differences were detected for safety outcomes (P > .05 for all), including non-cardiovascular deaths (risk ratio 1.08, 95% CI .76–1.54). Conclusions: This updated meta-analysis of RCTs demonstrated a substantial reduction in MACE, MI, ischaemic stroke, and recurrent coronary revascularization with colchicine compared with placebo. Therefore, the results support the use of colchicine to reduce recurrent cardiovascular events.

Although colchicine, a natural product, is one of the oldest drugs still currently available, its possible functions seem to be surprisingly not well-known. Beyond its present medicinal use (gout, familial Mediterranean fever, Behcet’s disease, chondrocalcinosis and other crystal arthritis), numerous other conditions have been recently proposed for the use of this drug, including pericardial diseases. However, colchicine appears as a double-edged sword, with underestimated toxicity and frequent side effects. In this review, we present the main pharmacologic features of this drug, with an emphasis on toxicity and highlight its possible applications in the cardiovascular field.