Article Archive
Highlights Report: 2014 FH Global Summit
The FH Global Summit offers a unique opportunity for all players in the healthcare arena, academia, government and patient advocacy groups, to act together to catalyse progress in FH care. Sooner not later: Children are the driver for improving FH care Top of the agenda…
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Unmet clinical needs in cholesterol lowering
Recent decades has seen marked improvement in reducing rates of heart disease and stroke (cardiovascular disease), particularly in developed nations.1 High levels of low-density lipoprotein cholesterol (LDL-C), or ‘bad cholesterol’ are considered a major risk factor for cardiovascular disease. International guidelines state that reduction of…
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PCSK9 inhibition
A raised level of low-density lipoprotein cholesterol (LDL-C) is one of the most important risk factors for cardiovascular disease. Despite success in recent decades in lowering LDL-C with statins and other lipid-lowering drugs, considerable risk remains for future cardiovascular events even in people who are…
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Familial hypercholesterolaemia (FH)
Why is cholesterol important? Cholesterol, with other fats such as triglycerides, plays a vital role in the structure and function of cells. However, too much cholesterol in the blood (hypercholesterolaemia) is a risk factor for early heart disease, heart attack and stroke. Cholesterol is transported…
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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…
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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…
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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;…
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RUTHERFORD-2 in brief
RUTHERFORD-2 was a large, randomised, placebo-controlled trial of the PCSK9 inhibitor, evolocumab, in 331 patients with heterozygous familial hypercholesterolaemia (mean LDL-C at baseline 3.9-4.2 mmol/L). All were on statins and 62% were also on ezetimibe. FH-causing mutations were identified in 80% of patients, most were…
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PCSK9 inhibitors and FH: future for standard of care?
Two recent trials in FH patients – RUTHERFORD-2 and TESLA – have raised the focus of the PCSK9 inhibitors in FH. In an accompanying Lancet editorial, Profs. Raul Santos (Sao Paulo, Brazil) and Gerald Watts (Perth, Australia) have intimidated that PCSK9 inhibitors might represent the…
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Heterogeneity in FH: What are the implications for management?
According to Professor Frederick Raal, South Africa, irrespective of genotype, what matters is reducing the LDL-C burden with lipid-lowering therapy. Familial hypercholesterolemia (FH) is an autosomal co-dominant disorder usually resulting from mutations in the LDL receptor (LDLR) gene characterised by elevated levels of LDL-cholesterol (LDL-C)…
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Alirocumab and Lp(a): Pooled analysis of Phase II trials
Alirocumab 150 mg every 2 weeks reduced Lp(a) by 30% compared with placebo, based on a pooled analysis of 3 phase II trials in patients treated with background lipid-lowering treatment.1 These findings were consistent with a pooled analysis of evolocumab phase II trials,2 suggesting a…
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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…
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How can we optimise PCSK9-targeted therapies?
Highly relevant to these discussions was how to optimise the use of PCSK9-targeted therapies, discussed from both European (Professor Luís Masana, University Rovira and Virgili, Reus-Tarragona, Spain) and North American (Professor Henry Ginsberg, Columbia University, New York, USA) perspectives, from the guidelines perspectives. There are…
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Evidence for the effects of PCSK9 beyond the liver
Evidence for the effects of PCSK9 beyond the liver was discussed by Professor Bertrand Cariou, INSERM UMR1087, l’Institut du Thorax, Nantes, France. A seminal paper showed that PCSK9 exerts hypocholesterolaemic effects via action in both the liver and intestine; in the latter case, PCSK9 modulates…
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Why new NLA guidelines for dyslipidaemia? A view from the authors
The US National Lipid Association (NLA) has just released recommendations for management of dyslipidaemia. Matthew K. Ito, Professor of Pharmacy Practice, Portland, Oregon and one of the lead authors, discusses thinking behind these recommendations, and what are the implications for clinicians. • Why has the…
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Reducing the burden of Disease and Death from Familial Hypercholesterolemia: A Call to Action
Familial hypercholesterolemia (FH) is a genetic disease characterized by substantial elevations of low-density lipoprotein cholesterol, unrelated to diet or lifestyle. Untreated FH patients have 20 times the risk of developing coronary artery disease, compared to the general population. Estimates indicate that as many as 1…
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ODYSSEY trials at ESC Congress Hotline
ESC Congress 2014: Lipids Hotline: ODYSSEY TRIALS Prof Alberto Zambon, University of Padua, Italy discusses the four ODYSSEY trials with the PCSK9 inhibitor alirocumab presented at ESC Congress Hotline Sunday. Addition of a new investigational agent – Alirocumab – to high doses of statins result…
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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…
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IMPROVE-IT: will it prove anything?
Professor Anthony S. Wierzbicki, London UK Comments on the IMPROVE-IT debate Cardiovascular disease (CVD) guidelines are emphasising the use of clinical outcome data on major vascular events (American Heart Association/American College of Cardiology)1 or hard CVD events alone (UK NICE)2 . They have begun to…
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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)?…
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