Lawrence Leiter

Background Ticagrelor reduced major adverse cardiovascular events (MACE) and increased bleeding in patients with type 2 diabetes mellitus (T2DM) and coronary artery disease. Limb events including revascularization, acute limb ischemia (ALI), and amputation are major morbidities in patients with T2DM and atherosclerosis. Objectives This study sought to determine the effect of ticagrelor on limb events. Methods Patients were randomized to ticagrelor or placebo on top of aspirin and followed for a median of 3 years. MACE (cardiovascular death, myocardial infarction, or stroke), limb events (ALI, amputation, revascularization), and bleeding were adjudicated by an independent and blinded clinical events committee. The presence of peripheral artery disease (PAD) was reported at baseline. Results Of 19,220 patients randomized, 1,687 (8.8%) had PAD at baseline. In patients receiving placebo, PAD was …

We thank Dr Jiang and colleagues for their interest in our publication, 1 which demonstrated the long-term safety and tolerability of inclisiran in patients with dyslipidemia. In their letter, Dr Jiang and colleagues noted that the incidence rate of muscle-related safety events with inclisiran was low compared with that reported with statin use in other clinical trial and outpatient settings. Importantly, the inclusion criteria for phase 3 trials with inclisiran specified that patients were receiving a maximally tolerated and stable dose of statins for $30 days before screening, and intolerance to any dose of statin was documented. 2 In a pooled analysis of phase 3 trials, the incidence of myalgia and musculoskeletal pain was similar between the inclisiran and placebo groups. 3

Aims Large outcome trials have demonstrated cardiovascular benefits of selected glucagon-like peptide-1 (GLP-1) receptor agonists. We examined coronary disease outcomes in the Harmony Outcomes trial of the GLP-1 receptor agonist albiglutide. Methods and results Harmony Outcomes was an event-driven, multicenter, double-blind, and placebo-controlled trial involving 9463 patients >40 years of age with type-2 diabetes and established atherosclerotic cardiovascular disease. It tested the effects of albiglutide on the occurrence of a composite primary endpoint, consisting of cardiovascular death, myocardial infarction (MI), or stroke. Within this post-hoc analysis, the effects of albiglutide on MI subtypes and other ischaemic endpoints were analysed. During the median-follow up of 1.6 years, a total of 421 patients (4.5%) experienced at least one MI, with 72 patients …

BackgroundREDUCE-IT (Reduction of Cardiovascular Events with Icosapent Ethyl–Intervention Trial) showed that icosapent ethyl (IPE) reduced major adverse cardiovascular events by 25%. Since the underlying mechanisms for these benefits are not fully understood, the IPE-PREVENTION CardioLink-14 trial (ClinicalTrials.gov: NCT04562467) sought to determine if IPE regulates vascular regenerative (VR) cell content in people with mild to moderate hypertriglyceridemia.MethodsSeventy statin-treated individuals with triglycerides ≥1.50 and <5.6 mmol/L and either atherosclerotic cardiovascular disease or type 2 diabetes with additional cardiovascular risk factors were randomized to IPE (4 g/day) or usual care. VR cells with high aldehyde dehydrogenase activity (ALDHhi) were isolated from blood collected at the baseline and 3-month visits and characterized with lineage-specific cell surface markers. The …

Time to clinical benefit with sotagliflozin in patients with type 2 diabetes and chronic kidney disease: Insights from the SCORED randomized trial Time to clinical benefit with sotagliflozin in patients with type 2 diabetes and chronic kidney disease: Insights from the SCORED randomized trial Eur J Heart Fail. 2024 Apr 17. doi: 10.1002/ejhf.3240. Online ahead of print. Authors Rahul Aggarwal 1 , Deepak L Bhatt 2 , Michael Szarek 3 4 , Lawrence A Leiter 5 , Christopher P Cannon 1 , Renato D Lopes 6 , Michael J Davies 7 , Phillip Banks 7 , Bertram Pitt 8 , Ph Gabriel Steg 9 10 Affiliations 1 Brigham and Women's Hospital Heart and Vascular Center, Harvard Medical School, Boston, MA, USA. 2 Mount Sinai Fuster Heart Hospital, Icahn School of Medicine at Mount Sinai, New York, NY, USA. 3 CPC Clinical Research and University of Colorado Anschutz Medical Campus, Aurora, CO, USA. 4 State University of New York …

BackgroundThe reduction of low-density lipoprotein cholesterol (LDL-C) with evolocumab, a fully human monoclonal antibody inhibitor of proprotein convertase subtilisin/kexin type 9 (PCSK9i), reduces the risk of major adverse cardiovascular events in patients with established atherosclerotic cardiovascular disease (ASCVD) with a prior MI, prior stroke, or symptomatic peripheral artery disease, with no offsetting safety concerns. The effect of evolocumab on CV outcomes in lower risk patients without a history of MI or stroke has not been explored.Study designVESALIUS-CV is a randomized, double-blind, placebo-controlled, global clinical trial designed to evaluate the effect of evolocumab on the risk of major cardiovascular events in patients at high cardiovascular risk but without a prior ischemic event. The study population consists of 12,301 patients with atherosclerosis or high-risk diabetes mellitus without a prior …

BackgroundST2 is involved in inflammation and fibrosis, and its soluble form (sST2) is associated with heart failure (HF) and cardiovascular (CV) outcomes. These associations have not been evaluated in large cohorts of patients (pts) with type 2 diabetes mellitus (T2DM).MethodssST2 was measured at baseline (Ella, Protein Simple) in 14,572 pts enrolled in DECLARE-TIMI 58, a randomized, placebocontrolled trial of dapagliflozin in pts with T2DM with or at high risk for atherosclerotic CV disease (median f/u= 4.2 years). Outcomes included adjudicated CV death (CVD) or hospitalization for HF (HHF) and MACE (CV death, myocardial infarction, or ischemic stroke). Hazard ratios were adjusted for age, sex, race, BMI, hypertension, prevalent CV disease, prior HF, eGFR, hs-cTnT, and NT-proBNP. Comparative effects of dapagliflozin vs. placebo were assessed by baseline sST2 quartiles.ResultsMedian baseline sST2 …

Background and aimsInclisiran, an siRNA therapy, consistently reduces low-density lipoprotein cholesterol (LDL-C) with twice-yearly dosing. Potential cardiovascular benefits of implementing inclisiran at a population level, added to statins, were evaluated through simulation.MethodsFor each participant in the ORION-10 and ORION-11 trials comparing inclisiran with placebo, baseline 10-year cardiovascular risk was estimated using the SMART equation. The time-adjusted LDL-C difference from baseline observed 90–540 days after baseline was assumed to persist and used to estimate potential reduction in 10-year cardiovascular risk. Impact on 500,000 ORION-like individuals was simulated with Monte-Carlo.ResultsMean baseline LDL-C and predicted 10-year major vascular risk among patients randomized to inclisiran (n = 1288) versus placebo (n = 1264) were 2.66 mmol/L versus 2.60 mmol/L and 24.9 …