News
PACMAN-AMI sub study provides further insights on PCSK9i plaque effects
Treating patients with non-obstructive lesions after acute myocardial infarction (AMI) with alirocumab leads to significant regression of angiographic diameter stenosis (DS%) but does not affect quantitative flow rate (QFR), according to results of a prespecified substudy of PACMAN-AMI (NCT03067844).1 This has led the trial investigators…
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AT-TARGET-IT: Real world data show high adherence to PCSK9 inhibitors
Real world data from the AT-TARGET-IT multicentre, observational registry in Italy have shown substantial reductions in LDL-cholesterol (LDL-C) and high levels of LDL-C target achievement with PCSK9 inhibitors (PCSK9i), leading to very high adherence and therapy persistence.1 Recently reported results from 798 patients enrolled in…
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Genetic variants in PCSK9 gene not linked to heart failure
New data which do not show any association between PCSK9 loss-of-function variants and changes in cardiac structure or function, or heart failure (HF), are providing reassuring evidence in relation to PCSK9 inhibition.1 The results, reported in JAMA Cardiology, come from a nested case-control study of…
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Do men respond better to PCSK9 inhibition than women?
Accumulating evidence from real-world studies suggests that men may get a greater reduction in LDL-cholesterol (LDL-C) with a PCSK9 inhibitor than women.1,2 However, questions have been raised about whether women are less aggressively treated than men.2 Results of a meta-analysis of six real-world studies with…
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New clues to PCSK9-LDL receptor degradation mechanism
Fresh insights into the molecular mechanism for the degradation of the PCSK9-LDL receptor (LDLR) complex are provided in a new study published in Molecular Metabolism (1). Researchers led by Professor Nabil Seidah (Université de Montréal, Canada) had previously suggested that the M2 subdomain of the C-terminal Cys/His-rich-domain…
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CLEAR OUTCOMES: Topline data show bempedoic acid reduces cardiovascular events
In a press release (1), Esperion announced that the landmark Cholesterol Lowering via Bempedoic acid, an ACL-Inhibiting Regimen (CLEAR) Outcomes trial has met the primary endpoint, with a statistically significant and clinically meaningful reduction in the primary endpoint. This was a 4-part composite of major…
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Lipoprotein(a) and atrial fibrillation – Is there a link?
PCSK9 Forum Co-editors Professors John Chapman and Henry Ginsberg discuss recent data. Atrial fibrillation (AF) is the most common arrhythmia, affecting about 0.5% (circa one in 200) of the worldwide population (1). Moreover, as populations age, prevalence has increased dramatically (2). Due to the associated risk…
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OCEAN(a)-DOSE: Olpasiran shows substantial lipoprotein(a) reduction
News from the American Heart Association Scientific Sessions 2022 In the OCEAN(a)-DOSE trial, treatment with olpasiran, a small interfering RNA (siRNA) agent targeting apolipoprotein(a), reduced lipoprotein(a) [Lp(a)] by up to 100%. The study was simultaneously published in the New England Journal of Medicine (1). In…
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Reducing residual risk: Are cholesterol crystals the next target?
Professor John Chapman Sorbonne University, Pitié-Salpetrière University Hospital, National Institute for Health and Medical Research (INSERM), Paris France Cardiovascular disease is the worldwide leading cause of mortality, responsible for about one-third of all deaths (1). Much of this burden is attributable to atherosclerotic cardiovascular disease…
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Trial with CRISPR PCSK9 treatment underway
The first trial of VERVE-101, a novel gene editing treatment that permanently turns off the PCSK9 gene in the liver to lower LDL cholesterol, is now underway in New Zealand (NCT05398029)(1). The trial is recruiting patients with heterozygous familial hypercholesterolaemia (FH) caused by an LDLR…
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Do PCSK9 inhibitors have a role in sepsis?
Sepsis poses a major global burden affecting over 50 million people and contributing to over 11 million deaths (2017 data) (1). Even among people who survive, many endure substantial reduction in physical, emotional and cognitive quality of life. Current management strategies focus on early aggressive…
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RACING trial: Do we need to rethink LDL-lowering strategies in Asian high-risk patients?
Guidelines recommend maximal tolerable statin therapy as the foundation of LDL cholesterol lowering in patients with atherosclerotic cardiovascular disease (ASCVD), ideally in combination with non-statin therapeutic options (1,2). While this strategy is undoubtedly effective, there may be concerns regarding possible side effects with high-intensity statin…
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More reassurance on the safety of PCSK9 inhibitors
The latest analysis of the Food and Drug Administration’s adverse event reporting system (FAERS) reinforced the safety of alirocumab and evolocumab. The FAERS is a database containing information on adverse event and medication error reports submitted to the Food and Drug Administration, which supports post-marketing…
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News from ACC.22 – New insights from ORION-10 and ORION-11: inclisiran effective in post-MI patients
Inclisiran was effective in lowering LDL cholesterol and generally well tolerated in patients with a prior myocardial infarction (MI), irrespective of the timing of MI, according to latest data from the ORION-10 and ORION-11 studies. Inclisiran is a small interfering ribonucleic acid (siRNA) therapeutic targeting…
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News from ACC.22 late breaking trials: Results from the APOLLO trial with new RNA therapeutic
Results from the APOLLO trial showed that single doses of SLN360, an investigational short interfering RNA (siRNA), resulted in dose-dependent lowering of plasma lipoprotein(a) [Lp(a)] concentration in adults with high Lp(a) and no pre-existing cardiovascular disease. The trial was simultaneously published in the Journal of…
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News from ACC.22 – Long-term data from HAUSER-OLE in paediatric familial hypercholesterolaemia
Results from the HAUSER Open-Label Extension Study (HAUSER-OLE) (1) show that treatment with evolocumab was well tolerated, safe, and led to substantial reduction in LDL cholesterol in children with heterozygous familial hypercholesterolaemia (FH). As previously reported on PCSK9 Forum, HAUSER-RCT evaluated the efficacy and safety…
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Consider familial hypercholesterolaemia in young heart attack survivors
Familial hypercholesterolaemia (FH) was more than 30-fold more prevalent among young people surviving an acute coronary syndrome (ACS) compared with the general population, according to this French report. These findings reinforce the need to investigate the possibility of FH in these individuals. Heterozygous FH is…
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Lessons from the HEYMANS registry: do we need to lower LDL thresholds for initiating a PCSK9 inhibitor?
Insights from the HEYMANS registry show that criteria for initiation of the PCSK9 inhibitor in real-world practice are far from optimal. The 2019 European Society of Cardiology/European Atherosclerosis Society (ESC/EAS) guidelines for management of dyslipidaemia underline the need for combination therapy in high-risk individuals to…
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New trials: Inclisiran investigated in adolescents with familial hypercholesterolaemia
Trials of PCSK9-targeted therapies have predominantly focused on adults at increased cardiovascular risk due to elevated LDL cholesterol levels. In the setting of familial hypercholesterolaemia (FH), in which individuals have elevated LDL cholesterol levels from birth, it makes sense to prioritize initiation of treatment in…
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Update from FOURIER: Evolocumab provides benefit in patients with prior PCI
In this latest analysis from FOURIER (Further Cardiovascular Outcomes Research With PCSK9 Inhibition in Subjects With Elevated Risk) (1), evolocumab treatment was associated with significant clinical benefit in patients with prior percutaneous coronary intervention (PCI), who are at high residual risk for multiple types of…
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