News
First antisense PCSK9 inhibitor terminated
To date, strategies for PCSK inhibition have focused primarily on targeting PCSK9 using monoclonal antibodies, which offer advantages in terms of high potency and specificity, long half-life, and low potential for drug-drug interactions. The potential of antisense inhibition of PCSK9 has been a focus of…
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PCSK9 inhibition: a role in treating sepsis?
Microbial cell walls contain pathogen lipids, such as lipopolysaccharide, which not only act as ligands for innate immune receptors, but also trigger the inflammatory response during sepsis (1). These pathogen lipids are mainly cleared by hepatic uptake, a process which also involves the low-density lipoprotein…
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Peripheral arterial disease affects 1 in 5 FH patients
According to a new study from Brazil, nearly 1 in 5 patients with heterozygous familial hypercholesterolaemia (FH, inherited high cholesterol) have peripheral arterial disease (PAD), as detected by ankle-brachial index (ABI). This prevalence was 6-fold higher than in controls with normal cholesterol. Importantly, more than…
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New Grant Opportunities from the IAS
The International Atherosclerosis Society is pleased to announce that the IAS and Pfizer Independent Grants for Learning & Change are continuing their collaboration on offering new grant opportunities. The current collaborative effort addresses the topic of Lipid Management in High-Risk Patients; specifically, we will…
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FDA approval for alirocumab
Alirocumab is the first PCSK9 inhibitor approved by the US Food and Drug Administration (FDA). In an announcement on Friday 24th July, alirocumab (Praluent®) was approved as an adjunct to diet and maximally tolerated statin therapy for the treatment of adults with heterozygous familial hypercholesterolemia…
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PCSK9 inhibitor evolocumab first approved in Europe
Evolocumab is the first PCSK9 inhibitor to be approved in Europe for the treatment of patients with uncontrolled hypercholesterolaemia who require additional intensive low-density lipoprotein (LDL) cholesterol reduction. This marks the first time that a PCSK9 inhibitor has been approved in the world. Specifically, the…
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Science News: Leptin and PCSK9
Leptin is a cytokine-like hormone that plays a key role in the regulation of energy metabolism, body weight, and lipid metabolism. The effects of leptin on PCSK9 expression were investigated in an animal model (leptin deficient ob/ob mice), as well as in humans with lipodystrophy,…
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DESCARTES: No adverse effect on glycaemic control with evolocumab
Evolocumab was effective and well tolerated over 52 weeks with no adverse signal for glycaemic control or new onset type 2 diabetes in patients with pre-existing dysglycaemia or metabolic syndrome. This analysis from DESCARTES included 120 subjects with type 2 diabetes, 293 with impaired fasting…
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Good news for PCSK9 inhibitors in diabetes patients
Findings reported for both evolocumab and alirocumab indicate promise for the PCSK9 inhibitors in patients with diabetes, with similar reductions in low-density lipoprotein (LDL) cholesterol as in nondiabetic patients. For evolocumab, there was also no difference in efficacy between 2-weekly and monthly regimens. A pooled…
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Start treatment early: Maximise benefit
FH is the most common inherited disease in the world – affecting about 30 million people worldwide – of whom only about 1% have been diagnosed. Therefore, it is critically important there is a global effort to start treatment early to prevent children ever developing…
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Dutch experience – Improving detection and care
In Europe, the Netherlands has proved that a concerted and integrated effort delivers effective detection of families at risk through cascade screening combined with early treatment – including considering statin therapy – in children the prognosis of people with FH is being significantly improved. Dr…
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PCSK9 inhibition and glucose homeostasis: new reassurance from human genetics
INSERM, UMR1087-CNRS UMR6291 & Université de Nantes, Faculté de Médecine, l’Institut du Thorax, and Department of Endocrinology, University Hospital of Nantes, Nantes, France The role of PCSK9 in glucose homeostasis is a critical issue, especially for the PCSK9 inhibitors (1), which are likely to be…
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Safety of LDL-lowering in FH children
One of the questions raised about managing children with familial hypercholesterolaemia (FH, inherited high cholesterol) is the long term safety of cholesterol-lowering treatments. There has been some concern that lowering cholesterol levels could interfere with hormone production and, potentially, future fertility. The current study addressed…
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Is the apoB/ PCSK9 ratio a new index for metabolic risk?
Evidence already implicates a role for elevated apolipoprotein (apo)B levels in the development of dysfunctional white adipose tissue associated with insulin resistance. A new study has shown that lower plasma PCSK9 levels strengthens this association. White adipose tissue plays a key role in the clearance…
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‘High-intensity cholesterol-lowering therapy’ versus ‘high-intensity statin therapy’
Is it time to change the paradigm? Recent guidelines come under scrutiny from Professor Luis Masana, University Rovira and Virgili, Reus-Tarragona, Spain The 2013 American College of Cardiology/American Heart Association (ACC/AHA) guidelines on cholesterol management for cardiovascular disease prevention identified four groups of patients that…
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LDL cholesterol lowering, PCSK9 and neurocognitive effects?
The possibility of neurocognitive effects with low-density lipoprotein (LDL) cholesterol lowering has been much debated. A new study (1) raises this issue again, suggesting increased risk of memory loss during the 30 days following the start of treatment, when comparing statin users and nonusers of…
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K-312: Joint inhibition of PCSK9 and CETP
A novel cholesteryl ester transfer protein (CETP) inhibitor – K-312 – has also been shown to decrease PCSK9 levels, raising the possibility of multi-target approach to low-density lipoprotein (LDL) cholesterol lowering with one agent. K-312 is currently in Phase I development. Preclinical studies using cholesterol-fed…
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LDL treatment choices in everyday practice too conservative
Results from a survey of more than 1,500 patients showed that physicians are too cautious in managing low-density lipoprotein (LDL) cholesterol in high cardiovascular risk patients, even when they are not at goal. The findings are particularly relevant in the light of recent favourable opinions…
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How will PCSK9 inhibitors be used in practice?
Professor Steven Nicholls, Professor of Cardiology at the University of Adelaide and the inaugural SAHMRI Heart Foundation Heart Health Theme Leader at the South Australian Health and Medical Research Institute, Australia, discusses the patients in whom these new treatments will be used initially and speculates…
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New cholesterol lowering drugs in news
The new PCSK9 inhibitors – drugs which reduce LDL-Cholesterol to previously manageable levels – are being reviewed by regulatory authorities worldwide. Why are they creating so much interest? Professor Philip Barter, President of the International Atherosclerosis Society comments.
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