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

IntroductionDespite 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).MethodsThe 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.ResultsA 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).DiscussionIn 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

Electronic health record-based facilitation of familial hypercholesterolaemia detection: Sensitivity of different algorithms in genetically confirmed patients

Familial hypercholesterolaemia (FH) is a disorder of LDL-cholesterol clearance, resulting in increased risk of cardiovascular disease. Recently, we developed a Dutch Lipid Clinic Network (DLCN) criteria-based algorithm to facilitate FH detection in electronic health records (EHR). In this study, we investigated the sensitivity of this and other algorithms in a genetically confirmed FH population. All patients with a healthcare insurance-related coded diagnosis of ‘primary dyslipidaemia’ between 2018-2020 were assessed for genetically confirmed FH. Data were extracted at the time of genetic confirmation of FH (T1) and during the first visit in 2018-2020 (T2). We assessed the sensitivity of algorithms on T1 and T2 for DLCN≥6 and compared to other algorithms (FAMCAT, MEDPED, and Simon Broome [SB]) using EHR-coded data and using all available data (i.e., including non-coded free text). 208 patients with genetically confirmed FH were included. The sensitivity (95% CI) on T1 and T2 with EHR-coded data for DLCN≥6 was 19% (14-25%) and 22% (17-28%), respectively. When using all available data, the sensitivity for DLCN≥6 was 26% (20-32%) on T1 and 28% (22-34%) on T2. For FAMCAT, the sensitivity with EHR-coded data on T1 was 74% (67-79%) and 32% (26-39%) on T2, whilst sensitivity with all available data was 81% on T1 (75-86%) and 45% (39-52%) on T2. For MEDPED and SB, using all available data, the sensitivity on T1 was 31% (25-37%) and 17% (13-23%), respectively. The FAMCAT algorithm had significantly better sensitivity than DLCN, MEDPED, and SB. FAMCAT has the best potential for FH case-finding using EHRs

The Effect of Years-Long Exposure to Low-Dose Colchicine on Renal and Liver Function and Blood Creatine Kinase Levels: Safety Insights from the Low-Dose Colchicine 2 (LoDoCo2) Trial

Background and Objective: The Low-Dose Colchicine-2 (LoDoCo2) trial showed that 2–4 years exposure to colchicine 0.5 mg once daily reduced the risk of cardiovascular events in patients with chronic coronary artery disease. The potential effect of years-long exposure to colchicine on renal or liver function and creatine kinase (CK) has not been systematically evaluated and was investigated in this LoDoCo2 substudy. Methods: Blood samples drawn from 1776 participants at the close-out visit of the LoDoCo2 trial were used to measure markers of renal function (creatinine, blood urea nitrogen [BUN]), liver function (alanine aminotransferase [ALT], γ-glutamyl transferase [GGT], bilirubin and albumin), and CK. Renal and liver function as well as hyperCKemia (elevated CK) were categorized to the degree of elevation biomarkers as mild, mild/moderate, moderate/severe, and marked elevations. Results: In total, 1776 participants (mean age 66.5 years, 72% male) contributed to this analysis, with a median exposure to trial medication of 32.7 months. Compared with placebo, colchicine was not associated with changes in creatinine and BUN but was associated with elevations in ALT (30 U/L vs. 26 U/L; p  5–10 × upper limit of normal [ULN]) in both treatment groups, and 6 (0.7%) colchicine-treated vs. 2 (0.2%) placebo-treated participants had moderate to marked CK elevations (> 5–10 × ULN). Conclusion: In chronic coronary artery disease, 2–4 years of exposure to colchicine 0.5 mg once daily was associated with small elevations in ALT and CK, but was not associated with changes in renal function. Trial Registration: https://www.anzctr.org.au; ACTRN12614000093684, 24 January 2014

Datasheet1_Colchicine and diabetes in patients with chronic coronary artery disease: insights from the LoDoCo2 randomized controlled trial.docx

IntroductionDespite 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).MethodsThe 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.ResultsA 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 interaction = 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).DiscussionIn 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.</p