Publications by authors named "Patrick M Moriarty"

Article Synopsis
  • Despite the availability of lipoprotein-lowering medications, some high-risk patients with persistent high cholesterol may need alternative treatments like lipoprotein apheresis (LA).
  • LA is particularly beneficial for individuals with familial hypercholesterolemia and not only lowers cholesterol but also improves heart function and reduces inflammation.
  • While studies show LA leads to better cardiovascular outcomes, its use in the U.S. is limited, and more research is needed on its benefits for certain kidney conditions.
View Article and Find Full Text PDF
Article Synopsis
  • The study investigates the relationship between triglyceride levels and the cardiovascular benefits of alirocumab compared to placebo in patients with recent acute coronary syndrome (ACS) who are on statin therapy.
  • Results showed that higher baseline triglyceride levels were linked to an increased risk of major adverse cardiovascular events (MACE), whereas alirocumab significantly lowered LDL cholesterol and reduced MACE risk.
  • While alirocumab led to a notable decrease in triglycerides, the reduction did not correlate with a lower risk of MACE, suggesting baseline triglyceride levels are more important for cardiovascular risk than reductions achieved through treatment.
View Article and Find Full Text PDF

Background: Homozygous familial hypercholesterolemia (HoFH) is a rare genetic disorder characterized by severely elevated low-density lipoprotein cholesterol (LDL-C) levels due to profoundly defective LDL receptor (LDLR) function. Given that severely elevated LDL-C starts in utero, atherosclerosis often presents during childhood or adolescence, creating a largely unmet need for aggressive LDLR-independent lipid-lowering therapies in young patients with HoFH. Here we present the first evaluation of the efficacy and safety of evinacumab, a novel LDLR-independent lipid-lowering therapy, in pediatric patients with HoFH from parts A and B of a 3-part study.

View Article and Find Full Text PDF

Purpose Of Review: Familial hypercholesterolemia (FH) and hyperlipoproteinemia(a) are relatively common disorders, posing a significant health burden due to increased risk of atherosclerotic cardiovascular disease (ASCVD). Development of electronic health record-based strategies with a linkage to the genetic test results has increased awareness, detection, and control of heritable lipid disorders. This review attempts to critically examine available data to provide a summary of the current evidence for lipoprotein apheresis in FH and elevated lipoprotein(a) (Lp(a)).

View Article and Find Full Text PDF
Article Synopsis
  • In 2022, the European Atherosclerosis Society released a consensus statement highlighting the link between lipoprotein(a) [Lp(a)] levels and an increased risk of atherosclerotic cardiovascular disease (ASCVD) and aortic stenosis.
  • A new risk calculator was introduced to help assess an individual's lifetime risk for ASCVD, particularly noting that those with high Lp(a) levels may be at greater risk than previously understood.
  • The statement also offers practical guidance for managing cardiovascular risk based on Lp(a) levels and addresses common questions regarding Lp(a) measurement and treatment options in everyday clinical practice.
View Article and Find Full Text PDF

Background Homozygous familial hypercholesterolemia (HoFH) is a rare, treatment-resistant disorder characterized by early-onset atherosclerotic and aortic valvular cardiovascular disease if left untreated. Contemporary information on HoFH in the United States is lacking, and the extent of underdiagnosis and undertreatment is uncertain. Methods and Results Data were analyzed from 67 children and adults with clinically diagnosed HoFH from the CASCADE (Cascade Screening for Awareness and Detection) FH Registry.

View Article and Find Full Text PDF

Severe hypertriglyceridemia (sHTG) is an established risk factor for acute pancreatitis. Current therapeutic approaches for sHTG are often insufficient to reduce triglycerides and prevent acute pancreatitis. This phase 2 trial ( NCT03452228 ) evaluated evinacumab (angiopoietin-like 3 inhibitor) in three cohorts of patients with sHTG: cohort 1, familial chylomicronemia syndrome with bi-allelic loss-of-function lipoprotein lipase (LPL) pathway mutations (n = 17); cohort 2, multifactorial chylomicronemia syndrome with heterozygous loss-of-function LPL pathway mutations (n = 15); and cohort 3, multifactorial chylomicronemia syndrome without LPL pathway mutations (n = 19).

View Article and Find Full Text PDF

Background: Bempedoic acid, an ATP citrate lyase inhibitor, reduces low-density lipoprotein (LDL) cholesterol levels and is associated with a low incidence of muscle-related adverse events; its effects on cardiovascular outcomes remain uncertain.

Methods: We conducted a double-blind, randomized, placebo-controlled trial involving patients who were unable or unwilling to take statins owing to unacceptable adverse effects ("statin-intolerant" patients) and had, or were at high risk for, cardiovascular disease. The patients were assigned to receive oral bempedoic acid, 180 mg daily, or placebo.

View Article and Find Full Text PDF
Article Synopsis
  • Severe hypertriglyceridemia often results from genetic factors, including rare pathogenic variants and common genetic variations assessed via polygenic risk scores (PRS).
  • In a study of 363 patients, those with both pathogenic variants and high PRS had a significantly increased risk of very severe hypertriglyceridemia and acute pancreatitis, compared to those without these genetic risk factors.
  • The findings suggest that genetic testing could be valuable in identifying patients at high risk for pancreatitis, potentially guiding targeted treatment strategies for hypertriglyceridemia.
View Article and Find Full Text PDF

Elevated red blood cell distribution width (RDW) is associated with increased risk for major adverse cardiovascular events (MACE) and death in patients with cardiovascular disease. The ODYSSEY OUTCOMES trial compared alirocumab with placebo in 18,924 patients with recent acute coronary syndrome (ACS) and elevated atherogenic lipoproteins despite optimized statin treatment. This post hoc analysis determined whether RDW independently predicts risk of MACE and death in patients after recent ACS, whether RDW influences MACE reduction with alirocumab, and whether alirocumab treatment affects RDW.

View Article and Find Full Text PDF
Article Synopsis
  • * It recommends testing Lp(a) levels in adults, especially those with a family history of high Lp(a) or premature ASCVD, and suggests aggressive management of cardiovascular risk factors in the absence of specific Lp(a)-lowering therapies.
  • * The statement underscores the need for further research into Lp(a)-lowering treatments while recognizing Lp(a) as a causal risk factor for cardiovascular conditions, reinforcing
View Article and Find Full Text PDF

Purpose Of Review: Lipoprotein (a) [Lp(a)] is a likely causal risk factor for atherosclerotic cardiovascular disease (ASCVD) and aortic valve disease, confirmed by Mendelian randomization. With reliable assays, it has been established that Lp(a) is linearly associated with ASCVD. Current low-density lipoprotein cholesterol (LDL-C) lowering therapies do not or minimally lower Lp(a).

View Article and Find Full Text PDF

Background: Olezarsen is a hepatocyte-targeted, GalNAc-modified antisense oligonucleotide that decreases plasma levels of apolipoprotein C-III (apoC-III) and triglyceride-rich lipoproteins (TRLs).

Objective: To define the effect of olezarsen on NMR-derived lipoprotein particle size and concentration.

Methods: Patients (n=114) with or at risk for atherosclerotic cardiovascular disease and fasting triglycerides ≥200 and <500 mg/dL received olezarsen (10 or 50 mg every 4 weeks, 15 mg every 2 weeks, or 10 mg every week) or saline placebo subcutaneously for 6-12 months.

View Article and Find Full Text PDF

The extent of intervention effects on carotid intima-media thickness (CIMT) can predict the degree of atherosclerotic cardiovascular risk-reduction. We hypothesized that regular lipoprotein apheresis over the course of 10 years might slow down progression of CIMT in patients with severe hypercholesterolemia. This case series describes 10 Caucasian patients (mean age 60 ± 9 years, 70% female, 80% statin intolerant) with a severe hypercholesterolemia phenotype treated with lipoprotein apheresis between 2005 and 2020 (mean duration, 10 ± 4 years).

View Article and Find Full Text PDF

Purpose Of Review: Lipoprotein(a) (Lp[a]) is a likely causal risk factor for atherosclerotic cardiovascular disease (ASCVD) and aortic valve disease, confirmed by Mendelian randomization. With reliable assays, it has been established that Lp(a) is linearly associated with ASCVD. Current low-density lipoprotein cholesterol (LDL-C) lowering therapies do not or minimally lower Lp(a).

View Article and Find Full Text PDF

Compelling evidence supports a causal role for lipoprotein(a) (Lp(a)) in cardiovascular disease. No pharmacotherapies directly targeting Lp(a) are currently available for clinical use. Here we report the discovery and development of olpasiran, a first-in-class, synthetic, double-stranded, N-acetylgalactosamine-conjugated small interfering RNA (siRNA) designed to directly inhibit LPA messenger RNA translation in hepatocytes and potently reduce plasma Lp(a) concentration.

View Article and Find Full Text PDF

Aims: Hypertriglyceridaemia is associated with increased risk of cardiovascular events. This clinical trial evaluated olezarsen, an N-acetyl-galactosamine-conjugated antisense oligonucleotide targeted to hepatic APOC3 mRNA to inhibit apolipoprotein C-III (apoC-III) production, in lowering triglyceride levels in patients at high risk for or with established cardiovascular disease.

Methods And Results: A randomized, double-blind, placebo-controlled, dose-ranging study was conducted in 114 patients with fasting serum triglycerides 200-500 mg/dL (2.

View Article and Find Full Text PDF
Article Synopsis
  • Thrombosis significantly impacts mortality for COVID-19 patients, and it may be linked to hypercoagulability driven by interleukin (IL)-6, which also raises lipoprotein(a) [Lp(a)] levels.
  • In a study of 219 hospitalized COVID-19 patients, researchers found that Lp(a) increased by an average of 16.9 mg/dl, with higher increases correlating with a greater incidence of venous thromboembolism (VTE) events.
  • The study concluded that elevated Lp(a) levels are closely associated with VTE in COVID-19 patients, suggesting that increased Lp(a) may contribute to a higher risk of thrombotic events during hospitalization.
View Article and Find Full Text PDF

Importance: Intense interest exists in novel ω-3 formulations with high bioavailability to reduce blood triglyceride (TG) levels.

Objective: To determine the phase 3 efficacy and safety of a naturally derived krill oil with eicosapentaenoic acid and docosahexaenoic acid as both phospholipid esters (PLs) and free fatty acids (FFAs) (ω-3-PL/FFA [CaPre]), measured by fasting TG levels and other lipid parameters in severe hypertriglyceridemia.

Design, Setting, And Participants: This study pooled the results of 2 identical randomized, double-blind, placebo-controlled trials.

View Article and Find Full Text PDF

Background: Volanesorsen is an antisense oligonucleotide that targets hepatic apolipoprotein C-III synthesis and reduces plasma triglyceride concentration. The aim of this study was to explore the safety and efficacy of volanesorsen in patients with multifactorial chylomicronaemia syndrome.

Methods: The COMPASS trial was a randomised, placebo-controlled, double-blind, phase 3 study done at 38 international clinical sites in Canada, France, Germany, the Netherlands, UK, and USA.

View Article and Find Full Text PDF

Lipoprotein(a) [Lp(a)] has risen to the level of an accepted cardiovascular disease risk factor, but final proof of causality awaits a randomized trial of Lp(a) lowering. Inhibiting apolipoprotein(a) production in the hepatocyte with ribonucleic acid therapeutics has emerged as an elegant and effective solution to reduce plasma Lp(a) levels. Phase 2 clinical trials have shown that the antisense oligonucleotide pelacarsen reduced mean Lp(a) levels by 80%, allowing 98% of subjects to reach on-treatment levels of <125 nmol/l (∼50 mg/dl).

View Article and Find Full Text PDF

Background: Lipoprotein apheresis (LA) tolerability is a key factor for the utilization of this therapy. Common reactions to LA are hypotension and nausea. Serious reactions include severe hypotension and anaphylactoid reactions (0.

View Article and Find Full Text PDF

Purpose Of Review: Summarize recent recommendations on clinical management of adults and youth with elevated lipoprotein(a) [Lp(a)] who are at-risk of or affected by cardiovascular disease (CVD).

Recent Findings: There is ample evidence to support elevated Lp(a) levels, present in approximately 20% of the general population, as a causal, independent risk factor for CVD and its role as a significant risk enhancer. Several guidelines and position statements have been published to assist in the identification, treatment and follow-up of adults with elevated levels of Lp(a).

View Article and Find Full Text PDF

Although statins play a pivotal role in the prevention of atherosclerotic cardiovascular disease, many patients fail to achieve recommended lipid levels due to statin-associated muscle symptoms. Bempedoic acid is an oral pro-drug that is activated in the liver and inhibits cholesterol synthesis in hepatocytes, but is not activated in skeletal muscle which has the potential to avoid muscle-related adverse events. Accordingly, this agent effectively lowers atherogenic lipoproteins in patients who experience statin-associated muscle symptoms.

View Article and Find Full Text PDF