Frederick J. Raal Articles

PCSK9 inhibition with a novel fusion protein

Reports from the 20th Virtual Closed Scientific Expert Meeting of the Editorial Board  Frederick Raal

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…

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)….

ESC 2021 Inclisiran in polyvascular disease

Polyvascular disease is a severe manifestation of atherosclerotic cardiovascular disease and an independent predictor of increased risk of cardiovascular events. Prof Derick Raal (University of the Witwatersrand, Johannesburg, South Africa) discusses findings from post hoc analyses from the ORION-9, -10 and -11 trials with the…

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

PCSK9 inhibitors and cognition back in the news

PCSK9 inhibitors and cognition back in the news Two recent reports have again raised the question of a possible link between the long-term effects of PCSK9 inhibition and cognitive adverse effects.  In the first report from the UK BioBank (1), the association of genetic variants…

No age limits for treating high cholesterol?

Prof Derick Raal (University of the Witwatersrand, Johannesburg, South Africa) discusses the latest evidence on this contentious question. Atherosclerosis is a progressive disease in which LDL cholesterol is a major driver. Supported by incontrovertible evidence that LDL is causal for atherosclerotic cardiovascular disease (ASCVD)(1,2), current…

HAUSER-RCT with evolocumab: what role in children with FH?

PCSK9 Forum Editor Professor Derick Raal (University of the Witwatersrand, Johannesburg, South Africa) comments on the findings of the HASUER-RCT study and potential implications for patient care. HAUSER-RCT is an important study for the care of children and adolescents with familial hypercholesterolaemia (FH). The study…

PCSK9 inhibition, low LDL cholesterol and lack of cognitive impairment: QED?

Prof Derick Raal, University of the Witwatersrand, Johannesburg, South Africa, discusses the latest data from FOURIER regarding cognitive safety. What is the take home message for clinicians? Clinicians have long been concerned about ‘going too low’ when prescribing lipid-lowering therapy. A key issue is whether…

Monogenic versus polygenic familial hypercholesterolaemia: how does cardiovascular risk compare?

Professor Derick Raal, University of the Witwatersrand, Johannesburg, South Africa Familial hypercholesterolaemia (FH, inherited high cholesterol) is one of the most common inherited disorders, affecting approximately one in every 250 people or over 30 million people worldwide.  FH is usually caused by pathogenic variants in…

Inclisiran: The Phase 3 trial

Reports from the 10th Closed Expert Meeting of the PCSK9 Education and Research Forum Frederick Raal 

Surfing the PCSK9 wave of discovery

Prof Derick Raal (University of Witwatersrand, Johannesburg, South Africa) gives his perspective on the newest ‘PCSK9 kids on the block’ amidst the wave of PCSK9 discovery. In 2012, there was the first clinical evidence of dramatic reductions in LDL cholesterol by inhibiting PCSK9 with monoclonal…

The lipoprotein(a) – LDL cholesterol conundrum

Prof Derick Raal, University of the Witwatersrand, Johannesburg, South Africa The last decade has seen a resurgence of interest in lipoprotein(a) [Lp(a)], the mysterious brother of LDL (low-density lipoprotein). Indeed, there is now established evidence that Lp(a) is an independent risk factor for cardiovascular disease…

Study shows no effect of circulating PCSK9 on beta-cell function

Uncertainties persist about the effect of PCSK9 deficiency on glucose homeostasis. Mendelian randomization studies have indicated a potential risk for new-onset diabetes mellitus, although data from clinical trials suggest rates are similar to those observed with statin (with or without ezetimibe).1-4 This experimental study aimed…

Inclisiran and the ORION Project

Reports from the 8th Expert Meeting of PCSK9 Forum Frederick Raal

New WOSCOPS analysis: Treat – don’t wait – if high LDL-C without heart disease

This important study confirms and supports the benefit of LDL cholesterol lowering with statin therapy for the primary prevention of atherosclerotic cardiovascular disease (ASCVD), especially in individuals with LDL cholesterol levels above 190 mg/dl (~5 mmol/L). ‘We need to start early and to treat more…

Treatment with evolocumab avoids the use of lipoprotein apheresis in high risk patients

Lipoprotein apheresis is an option in very high risk patients with uncontrolled LDL cholesterol levels despite maximally tolerated lipid lowering therapy. Typically, patients include those with severe familial hypercholesterolaemia (FH, inherited high cholesterol). Yet, while lipoprotein apheresis is effective in reducing LDL cholesterol there are…

Registry data gives insights into the real-world use of PCSK9 inhibitors

To date, evidence for the efficacy and safety of the PCSK9 monoclonal antibodies has been based on clinical trial experience. This report from a Dutch registry provides information relating to the use of these agents for management of patients with familial hypercholesterolaemia (FH, inherited high…

IMPROVE-IT: Further reassurance on very low LDL cholesterol

In a pre-specified analysis of IMPROVE-IT (Improved Reduction of Outcomes: Vytorin Efficacy International Trial), patients with LDL cholesterol < 30mg/dL or <0.78 mmol/l after 1 month on treatment had a similar safety profile and fewer cardiovascular events over 6 years than those at higher levels….

Are very low LDL-C levels on a PCSK9 inhibitor safe?

One of the key concerns of clinicians is whether the very low LDL cholesterol levels attained on a PCSK9 inhibitor are safe. Such concerns have been sparked by a recent meta-analysis which suggested a signal for adverse neurocognitive effects (1). These concerns were investigated in…