News

Peptide-based anti-PCSK9 vaccines around the corner?

Monoclonal antibody therapy to PCSK9 has been first off the block for PCSK9 therapeutics. Extensive clinical trial evidence has shown that these agents are effective, consistently lowering LDL cholesterol by 50-60%, alone or in combination with statin therapy, with no adverse signal to date. However,…

News from AHA Scientific Sessions 2014 – Heterozygous FH: Do we need a genetic diagnosis?

There was debate regarding the merits of genotype versus phenotype for diagnosis of heterozygous FH among the avenue of lipid posters.  In this report based on data from the RUTHERFORD-1 and -2 studies, the accuracy of clinical and genetic diagnosis was compared in patients with…

AHA Scientific Sessions – TAUSSIG analysis: Homozygous FH patients on lipid apheresis

Treatment with PCSK9 monoclonal antibody therapy results in further LDL-C lowering in patients with homozygous familial hypercholesterolaemia (FH ) receiving lipid apheresis, provided that they have at least one LDL receptor-defective mutation, according to data from the Trial Assessing Long-Term Use of PCSK9 Inhibition in…

AHA Scientific Sessions 2014: The Editors view of Day 1

PCSK9 Forum Editor Professor Derick Raal, University of the Witwatersrand, South Africa, discusses the take home messages from the Day 1 Latebreaker Trials IMPROVE-IT After much debate, IMPROVE-IT showed a significant benefit – although only just – with 6.4% reduction (p=0.016) in the primary outcome…

News from AHA Scientific Sessions Latebreakers IMPROVE-IT: support for the lower is better hypothesis

Results from IMPROVE-IT reaffirm the LDL hypothesis that ‘lower is better’.  As incremental benefit on cardiovascular outcomes was seen with the addition of non-statin therapy, IMPROVE-IT bodes well for the PCSK9-targeted therapies. The IMPROVE-IT trial has been the subject of much speculation over the last…

News from AHA 2014 ODYSSEY ALTERNATIVE in statin-intolerant patients

Alirocumab shows efficacy in statin intolerant patient with fewer muscle-related adverse events than atorvastatin. There was virtually no myalgia among patients who continued on open-label alirocumab, reinforcing that the fear of allocation to statin has had an enormous effect in the blinded study phase. Statin…

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…

Not only lower BUT but SOONER is better

2014 FH Global Summit: 13-14 October, New York, USA FH is highly treatable: lowering LDL-C helps in managing the disease process. Clearly, the focus for FH care needs to move from the acute setting to prevention. Identifying FH sooner rather than later is optimal for…

Overturning the 1%…Bridging the gaps in care

2014 FH Global Summit: 13-14 October, New York, USA: Familial hypercholesterolaemia (FH) is a major clinical challenge for the 21st century. The European Atherosclerosis Society Consensus Panel has already made the case for FH being one of the most common inherited conditions, affecting about one…

Mind the Gap: How can we address the challenges in FH?

2014 FH Global Summit: 13-14 October, New York, USA Screening for FH needs new impetus. Family history and an elevated LDL-C are the two key screening criteria for suspected FH. The obvious role for screening for suspected FH lies with primary care. Insights from the…

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…

Rationale for TESLA and results

Low density lipoprotein cholesterol (LDL-C) can be significantly reduced in patients with a serious genetic disorder – homozygous familial hypercholesterolaemia (FH) – when a PCSK9 inhibitor evolocumab is added to statins and other lipid-lowering medications. Professor Frederick Raal explains the results of the TESLA study.

R46L variant: an important modifier of the FH phenotype?

Carriage of the PCSK9 R46L loss of function mutation in FH patients appears to counteract the effects of FH-causing LDL receptor mutations, leading an improved phenotype and protection against coronary heart disease. 46L is the most common occurring in exon 1 of the PCSK9 gene,…

Very low LDL-C levels and risk for haemorrhagic complications after ischaemic stroke: should we be worried with PCSK9-targeted therapy?

Results from this experimental model suggests that PCSK9 inhibition is unlikely to increase the risk of haemorrhagic complications after ischaemic stroke. Haemorrhagic transformation, a spectrum of ischaemia-related brain haemorrhage, is a complication of acute ischaemic stroke that occurs in 10-40% of patients, and is associated…

Take home messages from ACC2014

Results of studies presented in 2014, show that PCSK9 inhibitors: 1) very effectively reduce low density lipoprotein cholesterol (LDL-C); and 2) show consistently predictable safety profiles. The positive results of short-term studies are now being reported in longer terms and larger clinical studies, Dr Evan…

Do PCSK9 loss of function mutations have direct effects on atherogenesis?

Identification of PCSK9 loss of function (LOF) mutations has been a key driver for the development of PCSK9-targeted therapies. LOF mutations in the PCSK9 gene lead to an increase in the number of LDL receptors on the surface of liver cells, resulting in an increase…

ODYSSEY long term

Low density lipoprotein cholesterol (LDL-C) was reduced by 60% in patients treated an investigational PCSK9 inhibitor, Alirocumab in addition to statin therapy, for about 52 weeks in the ODYSSEY study. The lead investigator, Professor Jennifer Robinson discusses how this was translated into a reduction in…

What are the gaps in knowledge about the PCSK9 inhibitors

ODYSSEY FH and patient unmet needs

Less than 1% of people with familial hypercholesterolaemia (FH), the commonest genetic disorder in the world are diagnosed. As FH patients have significantly elevated levels of low-density lipoprotein cholesterol (LDL-C) their consequent risk of cardiovascular death is greatly increased. Therefore, the results of the ODYSSEY…

ODYSSEY FHI FHII

Fewer than 80% of familial hypercholesterolaemia (FH) patients achieved an LDL-C level of