Targeting with Olezarsen in Moderate Hypertriglyceridemia.

Background: Highly effective therapies to reduce triglyceride levels are lacking. Olezarsen is an -acetylgalactosamine-conjugated antisense oligonucleotide that targets the messenger RNA of apolipoprotein C-III, which inhibits triglyceride clearance.

Methods: In this phase 3, international, double-blind, randomized, placebo-controlled trial, we enrolled patients with moderate hypertriglyceridemia (triglyceride level, 150 to 499 mg per deciliter) and elevated cardiovascular risk or with severe hypertriglyceridemia (triglyceride level, ≥500 mg per deciliter) and randomly assigned them in a 1:3 ratio to a 50-mg or 80-mg cohort.

Impact of Optical Coherence Tomography-Based Post-PCI Physiology Assessment to Predict Clinical Outcomes: An ILUMIEN-IV Substudy.

Background: A novel optical coherence tomography (OCT)-based physiology assessment technique, virtual flow reserve (VFR), has been demonstrated to perform as a reliable surrogate for invasive physiology.

Objectives: The authors sought to examine the performance of post-percutaneous coronary intervention (PCI) VFR as a predictor of 2-year clinical outcomes independent from the OCT-based minimal stent area (MSA).

Methods: The ILUMIEN IV (Optical Coherence Tomography [OCT] Guided Coronary Stent Implantation Compared With Angiography: A Multicenter Randomized Trial in PCI) trial prospectively recruited 2,487 patients with diabetes or high-risk coronary lesions randomizing to OCT- vs angiography-guided drug-eluting stent implantation.

Olezarsen in patients with hypertriglyceridemia at high cardiovascular risk: Rationale and design of the Essence-TIMI 73b trial.

Background: Elevated triglycerides are an important risk factor for atherosclerosis. However, the magnitude of triglyceride lowering with currently available therapies is modest and the impact of triglyceride-lowering on atherosclerosis remains undefined. Olezarsen is an antisense oligonucleotide (ASO) targeting mRNA for apolipoprotein C-III (apoC-III), an inhibitor of triglyceride clearance.

Design and rationale of the CORE-TIMI 72a and CORE2-TIMI 72b trials of olezarsen in patients with severe hypertriglyceridemia.

Background: Severe hypertriglyceridemia (HTG), defined as a serum triglyceride (TG) concentration ≥500 mg/dl, is present in approximately 1 in every 100 individuals and carries direct clinical consequences, including pancreatitis, which can be life-threatening. Olezarsen is an investigational antisense oligonucleotide targeted to the mRNA for apolipoprotein C-III (apoC-III), a protein known to impair TG clearance by inhibiting lipoprotein lipase and the hepatic uptake of triglyceride-rich remnants. No dedicated trial has tested olezarsen in patients with severe HTG.

Management of Coronary Stent Underexpansion.

Coronary stent underexpansion is an important problem and limitation of percutaneous coronary intervention, adversely affecting both short- and long-term patient outcomes. Stent underexpansion occurs when a stent fails to expand adequately compared with the adjacent reference segment, resulting in inadequate luminal gain. Multiple studies suggest that stent underexpansion is associated with increased risks of in-stent restenosis, stent thrombosis, and myocardial infarction, resulting in recurrent symptoms, readmissions, repeat interventions, and increased mortality.

Epistaxis Versus Nonepistaxis Bleeding in Anticoagulated Patients With Atrial Fibrillation: Results From the ENGAGE AF-TIMI 48 Trial.

Background: Epistaxis is common with antithrombotic therapy and is often troublesome to patients, yet its frequency, severity, and outcomes are poorly characterized.

Methods And Results: Effective Anticoagulation with Factor Xa Next Generation in Atrial Fibrillation-Thrombolysis in Myocardial Infarction 48 (ENGAGE AF-TIMI 48) randomized 21 105 patients with atrial fibrillation and CHADS2 risk score ≥2 to higher-dose edoxaban regimen (60 mg daily, dose-reduced to 30 mg), lower-dose edoxaban regimen (30 mg, dose reduced to 15 mg, daily), or warfarin. Bleeds were adjudicated using International Society on Thrombosis and Haemostasis criteria.

RapidBrachyIVBT: A dosimetry software for patient-specific intravascular brachytherapy dose calculations on optical coherence tomography images.

Background: Coronary artery disease is the most common form of cardiovascular disease. It is caused by excess plaque along the arterial wall, blocking blood flow to the heart (stenosis). A percutaneous coronary intervention widens the arterial wall with the inflation of a balloon inside the lesion area and leaves behind a metal stent to prevent re-narrowing of the artery (restenosis).

ISR vs De Novo Lesion Treatment During OCT-Guided PCI: Insights From the LightLab Initiative.

Background: Long-term outcomes after percutaneous coronary intervention (PCI) for in-stent restenosis (ISR) are poor, yet limited granular procedural data exist evaluating lesion assessment, vessel treatment, and acute procedural outcomes.

Methods: The LightLab Initiative was a multicenter, prospective, observational study with contemporaneous procedural data collection during PCI procedures. Data were collected during PCIs performed by 48 interventional cardiologists at 17 US hospitals (2019-2021).

Application of the Win Ratio Method in the ENGAGE AF-TIMI 48 Trial Comparing Edoxaban With Warfarin in Patients With Atrial Fibrillation.

Background: Cardiovascular trials often use a composite end point and a time-to-first event model. We sought to compare edoxaban versus warfarin using the win ratio, which offers data complementary to time-to-first event analysis, emphasizing the most severe clinical events.

Methods: ENGAGE AF-TIMI 48 (Effective Anticoagulation With Factor Xa Next Generation in Atrial Fibrillation-Thrombolysis in Myocardial Infarction 48) was a double-blind, randomized trial in which patients with atrial fibrillation were assigned 1:1:1 to a higher dose edoxaban regimen (60/30 mg daily), a lower dose edoxaban regimen (30/15 mg daily), or warfarin.

Olezarsen for Hypertriglyceridemia in Patients at High Cardiovascular Risk.

Background: Reducing the levels of triglycerides and triglyceride-rich lipoproteins remains an unmet clinical need. Olezarsen is an antisense oligonucleotide targeting messenger RNA for apolipoprotein C-III (APOC3), a genetically validated target for triglyceride lowering.

Methods: In this phase 2b, randomized, controlled trial, we assigned adults either with moderate hypertriglyceridemia (triglyceride level, 150 to 499 mg per deciliter) and elevated cardiovascular risk or with severe hypertriglyceridemia (triglyceride level, ≥500 mg per deciliter) in a 1:1 ratio to either a 50-mg or 80-mg cohort.

Reductions in remnant cholesterol and VLDL cholesterol through inhibition of ANGPTL3 protein synthesis: an analysis from the TRANSLATE-TIMI 70 trial.

Aims: Remnant cholesterol and very low-density lipoprotein cholesterol (VLDL-C) are increasingly recognized risk factors for atherosclerotic disease with few therapeutic options. Angiopoietin-like 3 (ANGPTL3), a key protein in the metabolism of triglyceride-rich lipoproteins, is a promising target.

Methods And Results: TRANSLATE-TIMI 70 was a double-blind, placebo-controlled randomized trial testing seven dose regimens of vupanorsen, an antisense oligonucleotide against ANGPTL3, in adults with non-HDL-C ≥ 100 mg/dL and triglycerides 150-500 mg/dL.

Percutaneous Coronary Intervention Versus Coronary Artery Bypass Grafting in Patients With Left Main Disease With and Without Diabetes: Findings From a Pooled Analysis of 4 Randomized Clinical Trials.

Background: Diabetes may be associated with differential outcomes in patients undergoing left main coronary revascularization with percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG). The aim of this study was to investigate outcomes in patients with left main disease with and without diabetes randomized to PCI versus CABG.

Methods: Individual patient data were pooled from 4 trials (SYNTAX [Synergy Between PCI With Taxus and Cardiac Surgery], PRECOMBAT [Premier of Randomized Comparison of Bypass Surgery Versus Angioplasty Using Sirolimus-Eluting Stent in Patients With Left Main Coronary Artery Disease], NOBLE [Nordic-Baltic-British Left Main Revascularisation Study], and EXCEL [Evaluation of XIENCE Versus Coronary Artery Bypass Surgery for Effectiveness of Left Main Revascularization]) that randomized patients with left main disease to PCI or CABG.

Hepatic fat changes with antisense oligonucleotide therapy targeting ANGPTL3.

Background: Angiopoietin-like protein 3 (ANGPTL3) is a novel therapeutic target for hyperlipidemia. Vupanorsen, an antisense oligonucleotide targeting ANGPTL3, reduced triglycerides up to 57% in a phase 2b trial, but caused dose-dependent increases in hepatic fat fraction (HFF).

Objective: To determine the degree of HFF progression with escalating doses of vupanorsen, differential HFF increases in key patient subgroups, and the correlation between changes in HFF and liver enzymes.

Percutaneous Coronary Intervention vs Coronary Artery Bypass Graft Surgery for Left Main Disease in Patients With and Without Acute Coronary Syndromes: A Pooled Analysis of 4 Randomized Clinical Trials.

Importance: Patients with left main coronary artery disease presenting with an acute coronary syndrome (ACS) represent a high-risk and understudied subgroup of patients with atherosclerosis.

Objective: To assess clinical outcomes after PCI vs CABG in patients with left main disease with vs without ACS.

Design, Setting, And Participants: Data were pooled from 4 trials comparing PCI with drug-eluting stents vs CABG in patients with left main disease who were considered equally suitable candidates for either strategy (SYNTAX, PRECOMBAT, NOBLE, and EXCEL).

OCT utilization: Summary statistics from the LightLab clinical initiative.

Objectives: The study describes the evolution of optical coherence tomography (OCT) adoption and performance during percutaneous coronary intervention (PCI) following implementation of a standardized LightLab (LL) workflow.

Background: The purpose of the LL Clinical Initiative was to evaluate the impact of a standardized workflow on physician efficiency, decision making, and image quality.

Methods: The LL Clinical Initiative is a multicenter, prospective, observational clinical program.

Randomized, Placebo-Controlled Phase 2b Study to Evaluate the Safety and Efficacy of Recombinant Human Lecithin Cholesterol Acyltransferase in Acute ST-Segment-Elevation Myocardial Infarction: Results of REAL-TIMI 63B.

Background: High-density lipoprotein plays a key role in reverse cholesterol transport. In addition, high-density lipoprotein particles may be cardioprotective and reduce infarct size in the setting of myocardial injury. Lecithin-cholesterol acyltransferase is a rate-limiting enzyme in reverse cholesterol transport.

Biomarker Prediction of Complex Coronary Revascularization Procedures in the FOURIER Trial.

Background: Biomarkers are known to predict major adverse cardiovascular events. However, the association of biomarkers with complex coronary revascularization procedures or high-risk coronary anatomy at the time of revascularization is not understood.

Objectives: We examined the associations between baseline biomarkers and major coronary events (MCE) and complex revascularization procedures.