Article Archive

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…

RUTHERFORD-2 slide deck now available

What are the gaps in knowledge about the PCSK9 inhibitors

Alirocumab

A 24-Week Study of Alirocumab as Monotherapy versus Ezetimibe: The First Phase 3 Data of a Proprotein Convertase Subtilisin/Kexin Type 9 Inhibitor One Year Open-Label Treatment with Alirocumab 150 mg Every Two Weeks in Heterozygous Familial Hypercholesterolemic Patients Effects of Alirocumab, a Fully Human Monoclonal…

Will PCSK9 monoclonal antibody therapy replace other classes of drug currently used in combination therapy both in FH and non-FH indications?

Frederick J. Raal FRCP, FRCPC, FCP(SA), Cert Endo, MMED, PhD Professor and Head, Division of Endocrinology & Metabolism Director, Carbohydrate and Lipid Metabolism Research Unit University of the Witwatersrand, South Africa Elevated LDL-cholesterol(LDL-C) is considered to be the pivotal causative factor for atherosclerosis and LDL-C…

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)…

PCSK9 inhibition in diabetes and metabolic syndrome: an analysis from OSLER

New findings, reported at the 2014 American Diabetes Association 74th Scientific Sessions,1 show thattreatment with the PCSK9 monoclonal antibody evolocumab reduced plasma levels of  low-density lipoprotein cholesterol (LDL-C) in hypercholesterolaemic patients with dysglycaemia or metabolic syndrome, without worsening glucose control. Lead author, Dr Robert R…

Rationale and Design of the Familial Hypercholesterolemia Foundation CAscade SCreening for Awareness and Detection

Familial hypercholesterolemia (FH) is a hereditary condition caused by various genetic mutations that lead to significantly elevated low-density lipoprotein cholesterol levels and resulting in a 20-fold increased lifetime risk for premature cardiovascular disease. Although its prevalence in the United States is 1 in 300 to…

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…

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…

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…

What does PCSK9 monoclonal antibody therapy offer to reduce residual CV risk?

Anthony S. Wierzbicki DM, DPhil, FRCPath Consultant, Department of Metabolic Medicine/Chemical Pathology Guy’s & St Thomas’ Hospitals St Thomas’ Hospital, London UK E-mail: [email protected] Cardiovascular disease (CVD) remains the greatest cause of world morbidity and mortality. Rates of CVD have decreased in parallel with reductions…

The role of PCSK9 inhibitors in FH

Monoclonal antibodies targeting PCSK9 have been shown to reduce low density lipoprotein cholesterol (LDL-C) by 30-40% in patients with familial hypercholesterolaemia (FH) who still have LDL receptors. Studies also show that the investigational drug, evolocumab was well tolerated, Dr Dirk Blom said.

Updates from the literature

Norsworthy PJ, Vandrovcova J, Thomas ER, Campbell A, Kerr SM, Biggs J, Game L, Soutar AK, Smith BH, Dominiczak AF, Porteous DJ, Morris AD, Scotland G, Aitman TJ: Targeted genetic testing for familial hypercholesterolaemia using next generation sequencing: a population-based study. BMC.Med.Genet. 2014, 15:70. Abstract:…

Why we need new approaches

Undoubtedly, LDL cholesterol is the priority target for intervention to reduce the risk of cardiovascular disease (CVD), as reaffirmed by the recent ACC/AHA guidelines for cholesterol management.1 Statins are at the cornerstone of lipid-modifying therapy. However, as recommended targets for LDL cholesterol have fallen as…

Is there a need for a unified definition for FH?

2014 FH Global Summit: 13-14 October, New York, USA: FH is clearly underdiagnosed and undertreated in the majority of countries.1 Given this status quo, would the development of a unified global definition of FH offer advantages for detection, management and health policy? In the FH…

Do the PCSK9 inhibitors have pleiotropic effects?

Experimental studies show that significant reductions in low density lipoprotein cholesterol (LDL-C) will significantly reduce inflammation which is important in Atherosclerosis (narrowing of the arteries) says Professor Erik Stroes.

Lp(a) and FH

Certain conditions, notably familial hypercholesterolaemia (FH), are associated with increased Lp(a) levels. The mechanism of this is so far undefined and may not directly involve the LDL receptor pathway. Holmes DT, Schick BA, Humphries KH, Frohlich J. Lipoprotein(a) is an independent risk factor for cardiovascular…

Lp(a) and CV risk

In epidemiological studies, levels of Lp(a) >125 nmol/L (~50 mg/dL), the 80th percentile for most populations, showed a consistent and independent positive association with CVD risk.1,2  Additionally, a large Mendelian randomisation study showed that a genetically determined doubling of Lp(a) was associated with a 22%…

About Lp(a)

Lipoprotein(a) [Lp(a)] is an LDL-like plasma lipoprotein rich in cholesterol. Lp(a) differs from LDL as it contains an additional protein, apolipoprotein(a) [apo(a)], which is attached via a single disulphide bond. Apo(a) itself comprises a series of loop structures called kringles, named after a Danish pastry….