Expert views

Lerodalcibep: What does LIBerate-HeFH tell us?

The Phase 3 LIBerate-HeFH trial showed that lerodalcibep significantly reduced LDL-cholesterol (LDL-C) in patients with heterozygous familial hypercholesterolaemia (HeFH) on background stable lipid lowering therapy (LLT). Professor Derick Raal discusses the data and explains what the results mean to practising clinicians. Lerodalcibep (LIB-003) consists of…

Verve-101: Where are we up to with PCSK9 gene editing?

VERVE-101 is a novel CRISPR base editing agent designed to knock out expression of the PCSK9 gene by changing a single DNA base, thereby turning off PCSK9 protein production in hepatocytes and lowering LDL-C. VERVE-101 consists of an mRNA for an adenine base editor and…

Apo(a) size and PAD revascularisation outcomes: What’s the link?

High Lp(a) increases the risk of peripheral arterial disease (PAD) and adverse limb events,1 and apo(a) is an essential component of Lp(a). Apo(a) is expressed as large and small isoforms, and small size is associated with higher Lp(a) levels and greater risk of cardiovascular disease.2,3…

Lepodisiran: What progress towards Lp(a) reduction?

Lepodisiran (LY3819469) is a short interfering RNA (siRNA) targeted at the mRNA for apolipoprotein A (apoA) – an essential component of lipoprotein a (Lp(a)). Elevated levels of Lp(a) are associated with atherosclerotic cardiovascular disease (ASCVD) and aortic stenosis, and Lp(a) measurement is recommended at least…

What’s new on the horizon for lipoprotein(a) therapies?

For too long an enigma, lipoprotein(a) [Lp(a)] has now taken centre stage on the strength of epidemiologic and genetic studies showing that an elevated Lp(a) level is a causal risk factor for cardiovascular disease. However, there is a major obstacle to the management of high…

What can we learn from the Homozygous Familial Hypercholesterolaemia International Clinical Collaboration registry?

Homozygous familial hypercholesterolaemia (HoFH) is the most severe presentation of this inherited lipid disorder, characterised by accelerated premature atherosclerotic cardiovascular disease due to the burden of extremely elevated LDL cholesterol levels from birth. Insights into management, however, are limited due to the rarity of the…

What does the future hold for CRISPR base editing of PCSK9?

Kiran Musunuru, Professor and Genetics Researcher at University of Pennsylvania, USA discusses the prospects for a one-shot “vaccination” against heart attacks, the leading cause of death worldwide. CRISPR (clustered regularly interspaced short palindromic repeats) gene editing has evolved rapidly to allow for testing in a…

Will evinacumab eliminate the need for LDL-apheresis in patients with homozygous FH?

Professor Derick Raal (University of the Witwatersrand, Johannesburg, South Africa) gives his view. Evinacumab is a remarkable therapy for individuals with homozygous familial hypercholesterolaemia (HoFH) and can result in a further 60% reduction in LDL cholesterol levels on top of aggressive lipid lowering therapy (1)….

LDL cholesterol lowering and effects on plaque: what can we learn from INTENSITY-HIGH?

INTENSITY-HIGH: Investigating the Lowest Threshold of Vascular Benefits from LDL Cholesterol Lowering with a PCSK9 mAb Inhibitor (Alirocumab) in Patients with Stable Cardiovascular Disease The landmark PCSK9 inhibitor trials – FOURIER and ODYSSEY OUTCOMES – established the cardiovascular benefits of lowering LDL cholesterol to very…

Combination therapy in familial hypercholesterolaemia: what can we gain from novel agents?

VIDEO: Do we treat high LDL-C in the ‘healthy’ elderly?