News
FOURIER: Evolocumab cuts MACE risk in those with obesity and ASCVD
The PCSK9 inhibitor evolocumab reduces the risk of major adverse cardiovascular events (MACE) in individuals with obesity and atherosclerotic cardiovascular disease (ASCVD), suggests a prespecified post-hoc analysis from the FOURIER trial. While it is known that evolocumab decreases the risk of MACE, the relationship between…
read more »
American College of Cardiology emphasises PCSK9 inhibitor role for PAD in diabetes
A new consensus statement from the American College of Cardiology (ACC) on the management of peripheral artery disease (PAD) in adults with diabetes has highlighted the role of PCSK9 inhibitors and bempedoic acid in lowering the risk of cardiovascular events and adverse limb outcomes. In…
read more »
US FDA approves novel PCSK9 inhibitor lerodalcibep for hypercholesterolaemia
The US Food and Drug Administration has approved the third generation PCSK9 inhibitor lerodalcibep-liga (Lerochol) for use in high-risk adults with elevated low-density lipoprotein cholesterol (LDL-C). Approval for the drug was granted in mid-December for patients with hypercholesterolemia, including heterozygous familial hypercholesterolemia. Lerodalcibep is a…
read more »
Study sheds light on how PCSK9 promotes LDLR degradation
The transmembrane protein low-density lipoprotein receptor (LDLR) is crucial in removing circulating low-density lipoprotein cholesterol (LDL-C) into the endosomes of a cell, where it is broken down, with LDLR returning to the cell surface. LDLR undergoes multiple such rounds of internalisation and recycling. When PCSK9…
read more »
CORALreef Lipids: Positive phase 3 trial results for enlicitide decanoate
The oral PCSK9 inhibitor, enlicitide decanoate, has shown positive topline results in the phase 3 CORALreef Lipids trial, according to its manufacturer Merck. Enlicitide decanoate, given as a daily pill, achieved all its primary and secondary endpoints in adults with hypercholesterolaemia on moderate and high…
read more »
PCSK9 targeting therapies safe and effective in FH, highlights meta-analysis
Treatments targeting PCSK9 significantly reduce low density lipoprotein cholesterol (LDL-C) and are well-tolerated in both adults and children with familial hypercholesterolaemia (FH), found a new meta-analysis. The systematic review and analysis, published in the journal Open Heart, included 4,282 adult and paediatric patients from 23…
read more »
FDA broadens evolocumab approval to include increased risk of MACE
The US Food and Drug Administration (FDA) has expanded the approved use of PCSK9 inhibitor, Repatha (evolocumab), to include adults at increased risk of major adverse cardiovascular events (MACE) because of uncontrolled levels of low density lipoprotein cholesterol (LDL-C). The change, made in August according…
read more »
VICTORION-Difference: Inclisiran effective for LDL-C in high CV risk patients
Inclisiran therapy brought more patients with hypercholesterolaemia at high or very high risk of cardiovascular (CV) events to early and sustained LDL-C goals with fewer adverse muscle symptoms than placebo when given in addition to individualised lipid-lowering treatments, showed a large, multicentre phase IV trial….
read more »
NEWTON-CABG CardioLink 5: Is evolocumab effective in graft vein disease?
Cholesterol-lowering by evolocumab did not reduce graft vein disease in patients in the two years following coronary artery bypass surgery, according to new findings. Results from the NEWTON-CABG CardioLink 5 trial were unveiled by principal investigator Professor Subodh Verma from St. Michael’s Hospital in Toronto,…
read more »
V-MONO trial of inclisiran monotherapy meets primary endpoints
The Phase 3 V-MONO study of inclisiran monotherapy in patients at low or moderate risk of atherosclerotic cardiovascular disease (ASCVD) has met its primary endpoints. Top-line data show that inclisiran treatment resulted in a clinically meaningful and statistically significant reduction in LDL-C compared to placebo…
read more »
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…
read more »
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…
read more »
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…
read more »
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…
read more »
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…
read more »
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…
read more »
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…
read more »
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…
read more »
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…
read more »
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…
read more »
