Article Archive

Professor Gerald Watts discusses the 10 countries project in FH

The International Atherosclerosis Society has begun a study in Asia and the Pacific Rim to provide the first comprehensive investigation of the worlds commonest genetic disorder, familial hypercholesterolaemia (FH) in the region. FH results in very high levels of low density lipoprotein cholesterol (LDL-C) and…

Rising to the Challenge: Implementing Models of Care in FH

Winthrop Professor Gerald F. Watts DSc PhD MD FRACP FRCP, Lipid Disorders Clinic, Cardiovascular Medicine, Royal Perth Hospital School of Medicine and Pharmacology, University of Western Australia. GPO Box X2213, Perth, WA 6847, Australia; E-mail: [email protected] While several guidelines, mostly based on expert opinion, have…

PCSK9: Opportunities for personalised medicine?

Personalised medicine shifts the focus from a ‘one-size-fits-all’ to patient-centred alternatives. This undoubtedly benefits both patients and healthcare budgets. Such an approach has already been integrated into other disciplines, such as oncology. Is such a strategy also relevant in the management of familial hypercholesterolaemia (FH)?…

What are the current unmet needs?

Despite statins, there are significantly unmet clinical needs in cholesterol lowering treatment. Statin do not effectively treat more than 50% of people with Familial Hypercholesterolaemia (FH) and other patients have intolerable side effects, says Professor Erik Stroes.

For which patients would you expect the PCSK9 monoclonal antibodies to be most useful?

Michel Farnier MD PhD Point Medical, Dijon, France Proprotein convertase subtilisin kexin type 9 (PCSK9) plays a key role in low-density lipoprotein (LDL) metabolism, mainly by enhancing degradation of LDL receptors in the liver. PCSK9 is a secreted protein and acts by reducing the amount…

Statins and plaque burden

The clinical benefit of LDL cholesterol lowering with statins has been conclusively demonstrated with a wealth of experience from primary and secondary prevention clinical trials.1,2 In addition, imaging studies have shown that statins have a favourable effect on atherosclerosis progression, either stabilising or even decreasing…

FH in the statin era: we need to do better

Despite the availability of generic statin therapy, cardiovascular disease accounts for 50% of all deaths in FH patients. Clinicians need to do better, argues Eric Bruckert, Institut E3M et IHU cardiométabolique (ICAN), Hôpital Pitié Salpêtrière, Paris, France. Familial hypercholesterolemia (FH) is a severe condition, which…

Unmet needs in children with FH

Identification and treatment to reduce low density lipoprotein cholesterol (LDL-C) of children with familial hypercholesterolaemia (FH) is vital to reduce the risk of cardiovascular death in early adulthood. FH is the most common genetic disorder in the world. Parents and healthcare professionals need to be…

FH detection in primary care: how can we do better?

FH is clearly underdiagnosed and undertreated.1  The question is how to best to address this challenge. FH is one of the most common genetically transmitted conditions, with about 1 in 200-250 people affected.1,2 In the UK, this translates to about 300,000 people affected ; however,…

Improving the management of the FH patient

Professor Raul Santos from Brazil says that the new therapies which inhibit PCSK9 to significantly reduce low density Lipoprotein Cholesterol (LDL-C) when given in addition to other cholesterol lowering drugs offer a very important advance in reducing cardiovascular risk in people with Familial Hypercholesterolemia (FH).

Lowering LDL-C : at what level would this impact the benefit vs. risk ratio?

Emeritus Research Professor, Institut de recherches cliniques de Montréal (IRCM), Canada Potent inhibitors of pro-protein convertase-subtilisin-kexin-9 (PCSK9) have the capacity to reduce plasma low-density lipoprotein cholesterol (LDL-C) to unprecedentedly low levels, especially if combined with statins. This discovery raises several important questions; how low should…

Do the PCSK9 monoclonal antibodies have neurocognitive adverse effects?

Evolocumab

ACC 2014 March 29th  MENDEL-2: http://www.pcsk9forum.org/mendel-2-2/ DESCARTES: http://www.pcsk9forum.org/descartes-durable-ldl-c-lowering-with-evolocumab/ RUTHERFORD-2: http://www.pcsk9forum.org/acc-2014-rutherford-2-evolocumab-in-heterozygous-fh/ LAPLACE-2: http://www.pcsk9forum.org/acc-2014-latebreaker-laplace-2-evolocumb-effective-in-patients-on-high-and-moderate-intensity-statins/ GAUSS-2: http://www.pcsk9forum.org/acc-2014-latebreaker-gauss-2-evolocumab-addresses-unmet-needs-in-statin-intolerance/  

Lipoprotein apheresis lowers plasma PCSK9

Lipoprotein apheresis is clearly important in the management of severe familial hyperchoelsterolaemia (FH). However, its use is not without practical and cost limitations. Evidence that lipoprotein apheresis has an additional benefit in lowering plasma PCSK9 levels, beyond effects on low-density lipoprotein cholesterol (LDL-C), suggests that…

PCSK9: From discovery to therapeutic applications

PUBMED abstract: http://www.ncbi.nlm.nih.gov/pubmed/24373748

Latest IMPROVE-IT commentary

PCSK9 monoclonal antibody therapy: pharmacodynamics, efficacy and safety

Webcast Prof Evan Stein, University of Cincinnati Medical Center, Cincinnati, Ohio, USA overviews the clinical development of PCSK9 monoclonal antibody therapy Report from State-of-the-Art PCSK9 Science: Current understanding and therapeutic perspectives Prof Evan Stein discusses the pharmacodynamics of the two most advanced PCSK9 monoclonal antibody…

TESLA in brief

TESLA was a randomised, double-blind, placebo-controlled trial of the PCSK9 inhibitor, evolocumab, in 50 patients (49 received treatment) with homozygous FH (mean LDL-C at baseline 9.0 mmol/L). All were on statins and 91% also received ezetimibe. LDL receptor mutations were identified in 45 (92%) patients;…

Mechanistic insights from PCSK9 LOF mutations

Mechanistic insights from PCSK9 LOF mutations with a particular focus on data from the Copenhagen studies, were discussed by Professor Anne Tybjaerg-Hansen, Rigshospitalet, Copenhagen University Hospital, and University of Copenhagen, Denmark. Seminal studies showed that carriage of LOF mutations was associated reduction in LDL cholesterol…

FH

2021: Integrated Guidance for Enhancing the Care of Familial Hypercholesterolaemia in Australia https://pubmed.ncbi.nlm.nih.gov/33309206/ 2021: Update of the Brazilian Guideline for Familial Hypercholesterolemia https://pubmed.ncbi.nlm.nih.gov/34709306/ 2019: NICE. Familial hypercholesterolaemia: identification and management https://www.guidelines.co.uk/genetic-conditions/nice-fh-guideline/453843.article 2018: Canadian Cardiovascular Society Position Statement on Familial Hypercholesterolemia: Update 2018 https://pubmed.ncbi.nlm.nih.gov/30527143/ 2017: Guidelines…