Zodasiran, an RNAi Therapeutic Targeting ANGPTL3, for Mixed Hyperlipidemia

New England Journal of Medicine, Journal Year: 2024, Volume and Issue: 391(10), P. 913 - 925

Published: May 29, 2024

Angiopoietin-like 3 (ANGPTL3) inhibits lipoprotein and endothelial lipases hepatic uptake of triglyceride-rich remnants.

Language: Английский

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Plozasiran for Managing Persistent Chylomicronemia and Pancreatitis Risk

New England Journal of Medicine, Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 2, 2024

BackgroundPersistent chylomicronemia is a genetic recessive disorder that classically caused by familial syndrome (FCS), but it also has multifactorial causes. The associated with the risk of recurrent acute pancreatitis. Plozasiran small interfering RNA reduces hepatic production apolipoprotein C-III and circulating triglycerides.MethodsIn phase 3 trial, we randomly assigned 75 patients persistent (with or without diagnosis) to receive subcutaneous plozasiran (25 mg 50 mg) placebo every months for 12 months. primary end point was median percent change from baseline in fasting triglyceride level at 10 Key secondary points were mean values months, changes incidence pancreatitis.ResultsAt baseline, 2044 per deciliter. At (the point) −80% 25-mg group, −78% 50-mg −17% group (P<0.001). key showed better results groups than including pancreatitis (odds ratio, 0.17; 95% confidence interval, 0.03 0.94; P=0.03). adverse events similar across groups; most common abdominal pain, nasopharyngitis, headache, nausea. Severe serious less placebo. Hyperglycemia occurred some prediabetes diabetes baseline.ConclusionsPatients who received had significantly lower levels those (Funded Arrowhead Pharmaceuticals; PALISADE ClinicalTrials.gov number, NCT05089084.)

Language: Английский

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Epidemiology and longitudinal course of chylomicronemia: Insights from NHANES and a large health care system

Journal of clinical lipidology, Journal Year: 2025, Volume and Issue: unknown

Published: March 1, 2025

Chylomicronemia is characterized by fasting triglyceride (TG) ≥1000 mg/dL; its longitudinal course not well studied. Using National Health and Nutrition Examination Survey (NHANES) data (1999-2018; n = 21,998), we determined chylomicronemia prevalence temporal trend. Mayo Clinic (4,524,506 TG measurements for 1,294,044 individuals), studied the ascertained persistent (PC), defined as mg/dL in more than half individuals with ≥3 measurements. We used logistic regression to assess factors associated PC. In NHANES, of was 0.20% overall, higher men (0.32%) Hispanics (0.33%). declined from 0.34% 1999-2004 0.11% 2013-2018, while lipid-lowering pharmacotherapy use patients increased 5.3% 51.9%. data, 5618 (0.43%) had at least 1 episode chylomicronemia. Of these, 8.8% (390 4443 measurements) met operational definition <150 mg/dL, 1.3% a diagnosis acute pancreatitis, 0.6% chronic pancreatitis. Respective figures nonpersistent were 12.5% 5.1%, PC 26.2% 11.5%. Younger age, Hispanic ethnicity, prior levels US, ∼500 adults has ∼5500 Individuals have high occurrence pancreatitis may need effective treatment.

Language: Английский

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Impact of remnant cholesterol on short-term and long-term prognosis in patients with prediabetes or diabetes undergoing coronary artery bypass grafting: a large-scale cohort study

Cardiovascular Diabetology, Journal Year: 2025, Volume and Issue: 24(1)

Published: Jan. 8, 2025

Remnant cholesterol (remnant-C) contributes to atherosclerotic cardiovascular disease (ASCVD), particularly in individuals with impaired glucose metabolism. Patients metabolism and ASCVD remain at significant residual risk after coronary artery bypass grafting (CABG). However, the role of remnant-C this population has not yet been investigated. Adult patients prediabetes or diabetes undergoing isolated CABG were consecutively enrolled a longitudinal cohort between 2013 2018. The impact on short-term long-term outcomes was evaluated. included major perioperative complications. adverse cerebrovascular events (MACCEs). Remnant-C analyzed as both categorical continuous variable. Logistic regression, Cox restricted cubic spline analyses performed multivariate adjustments. In terms outcomes, elevated had higher incidence acute kidney injury (AKI) stage 2/3 (high vs. low remnant-C: 3.2% 2.4%; OR: 1.404, 95% CI 1.080-1.824). Each 1-standard deviation (SD) increase associated 16.6% AKI (OR: 1.160, 1.067-1.260). Long-term assessed median follow-up 3.2 years, during which 1,251 (9.3%) experienced MACCEs. 1-SD 6.6% MACCEs (HR: 1.066, 1.012-1.124), 7.1% all-cause death 1.071, 1.008-1.209), an 11.2% myocardial infarction 1.112, 1.011-1.222). These associations remained consistent when treated Importantly, association independent LDL-C levels; levels increased MACCE regardless whether ≤ 2.6 mmol/L > mmol/L. Subgroup analysis indicated that more pronounced insulin-treated patients. is CABG.

Language: Английский

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Current and Emerging Treatment Options for Hypertriglyceridemia: State-of-the-Art Review

Pharmaceuticals, Journal Year: 2025, Volume and Issue: 18(2), P. 147 - 147

Published: Jan. 23, 2025

Hypertriglyceridemia (HTG) is associated with a residual risk of atherosclerotic cardiovascular disease. Extremely elevated triglyceride (TG) concentrations, particularly due to familial chylomicronemia syndrome (FCS), pose for acute pancreatitis. Standard therapies statins, fibrates, omega-3 fatty acids, and niacin may be insufficient reduce TG levels improve clinical outcomes in patients HTG. Novel antisense oligonucleotides small interfering ribonucleic acids target the key modulators TG-rich lipoprotein catabolism. Among apolipoprotein C-III (apoC-III) inhibitors, olezarsen plozasiran appear safer alternatives volanesorsen regarding drug-induced thrombocytopenia FCS or severe After failure vupanorsen, new angiopoietin-like protein 3 (ANGPTL3) inhibitor, zodasiran, demonstrated potential decrease moderate Meanwhile, fibroblast growth factor 21 (FGF21) analog, pegozafermin, became another candidate treatment This comprehensive review outlines pharmacological targets metabolism, discusses international guidelines, summarizes latest evidence from trials provide insight into current emerging options primary

Language: Английский

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Novel RNA-Based Therapies in the Management of Dyslipidemias

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(3), P. 1026 - 1026

Published: Jan. 25, 2025

Pharmaceutical advancements and an improved understanding of pathophysiology have enabled innovative therapies for chronic conditions like dyslipidemia. This condition is marked by abnormalities in lipid homeostasis. Nucleic acid therapeutics, including antisense oligonucleotides small interfering RNAs, are novel management strategies that silence genes targeting mRNA. Antisense modify mRNA to inhibit protein production, whereas RNAs induce degradation via the RNA-induced silencing complex (RISC), thus offering promising treatments dyslipidemia atherosclerotic cardiovascular disease. Chemical modifications improve their stability targeting. RNA-based PCSK9, Lp(a), ApoC-III, ANGPTL3 hold transformative potential treating effectively. article discusses latest data from completed ongoing trials on RNA dyslipidemia, inclisiran, pelacarsen, olpasiran, zerlasiran, lepodisiran, volanesorsen, olezarsen, plozasiran, zodasiran, solbinsiran. Each therapy targets specific molecules while also significantly impacting other parameters. The results these indicate improvements risk reduction, with studies expected further refine role agents effective management.

Language: Английский

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Familial chylomicronemia syndrome and treatments to target hepatic APOC3 mRNA

Atherosclerosis, Journal Year: 2025, Volume and Issue: unknown, P. 119114 - 119114

Published: Jan. 1, 2025

Language: Английский

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Association of remnant cholesterol with unhealthy lifestyle and risk of coronary heart disease: a population-based cohort study

The Lancet Regional Health - Europe, Journal Year: 2025, Volume and Issue: unknown, P. 101223 - 101223

Published: Feb. 1, 2025

SummaryBackgroundUnhealthy lifestyle is a major risk factor for coronary heart disease, which may be explained by elevated remnant cholesterol. However, this question remains incompletely clarified. In study, we aimed to investigate whether cholesterol explains part of the excess myocardial infarction and disease in individuals with unhealthy lifestyle.MethodsWe included 104,867 (58,286 women 46,581 men) from Copenhagen General Population Study free at examination. During median follow-up 9.2 years, 2484 developed 3570 disease. To understand due on used mediation analyses.FindingsCurrent smoking, low physical activity, adherence dietary guidelines were all associated higher levels For current 15% (95% confidence interval: 9.7%–20%) 16% (11%–21%) Corresponding values activity 20% (13%–27%) 21% (15%–28%), 12% (6.6%–18%) 14% (8.0%–19%), respectively. Results similar men separately analyses where each additionally adjusted other three factors.InterpretationElevated an lifestyle. Clinically, these novel findings underline importance both promotion healthy primary prevention disease.FundingIndependent Research Fund Denmark; Johan Boserup Lise Boserups Grant; Medical Council.

Language: Английский

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Discordance Analyses Comparing LDL Cholesterol, Non-HDL Cholesterol, and Apolipoprotein B for Cardiovascular Risk Estimation

Atherosclerosis, Journal Year: 2025, Volume and Issue: 403, P. 119139 - 119139

Published: Feb. 18, 2025

Language: Английский

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The Year in Cardiovascular Medicine 2024: the top 10 papers in dyslipidaemias

European Heart Journal, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 30, 2025

Graphical AbstractThe top 10 papers in dyslipidaemias:Left hand side shows the lipid/lipopprotein targets and right what are new developments related to lipoprotein as discussed text.Open tabDownload slide

Language: Английский

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