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Frederick J. Raal Articles

The lipoprotein(a) – LDL cholesterol conundrum

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…

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

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…

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Inclisiran and the ORION Project

Inclisiran and the ORION Project

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

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

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…

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

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…

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

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…

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IMPROVE-IT: Further reassurance on very low LDL cholesterol

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….

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

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…

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Is baseline PCSK9 a determinant of LDL cholesterol lowering with a PCSK9 inhibitor?

Is baseline PCSK9 a determinant of LDL cholesterol lowering with a PCSK9 inhibitor?

Is baseline PCSK9 a determinant of LDL cholesterol lowering with a PCSK9 inhibitor? This report addresses this question by investigating the association between plasma PCSK9 and the LDL cholesterol reduction attained with the PCSK9 inhibitor evolocumab. The authors evaluated pooled data from 3,016 patients (40%…

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First data on familial hypercholesterolaemia in China

First data on familial hypercholesterolaemia in China

Most of the information relating to familial hypercholesterolaemia (FH, inherited high cholesterol) is from Caucasian populations. In Northern Europe, about 1 in 200-250 individuals have FH; results from the US are similar (1,2). However, there are many ‘black holes’ where there is no information on…

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No effect of PCSK9 inhibitors on new-onset diabetes

No effect of PCSK9 inhibitors on new-onset diabetes

Treatment with alirocumab for up to 18 months did not affect the incidence of new-onset diabetes, according to this pooled analysis of Phase III trials from the ODYSSEY programme.  These findings are in line with reports with evolocumab which showed no effect on glycaemic measures…

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PlayIs lipoprotein(a) a cause of clinical familial hypercholesterolaemia?

Is lipoprotein(a) a cause of clinical familial hypercholesterolaemia?

Familial hypercholesterolaemia (FH, inherited high cholesterol) is a common autosomal dominant condition which is characterized by raised LDL cholesterol, family history of dyslipidaemia, and early onset of coronary heart disease. Beyond mutations in the LDLR, APOB and PCSK9 genes, a new study from the University…

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PlayLow LDL-C, PCSK9 and dementia risk?

Low LDL-C, PCSK9 and dementia risk?

An ongoing debate among the experts is whether the very low levels of LDL cholesterol with PCSK9 inhibitor treatment might be associated with neurocognitive events. In fact, the debate predates the PCSK9 inhibitors, with statins linked with cognitive impairment (1-4). However, when the statin data…

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PlayTAUSSIG: Does adding evolocumab reduce cardiovascular events in homozygous FH?

TAUSSIG: Does adding evolocumab reduce cardiovascular events in homozygous FH?

84th European Atherosclerosis Society Congress, 29 May- 1 June, Innsbruck, Austria Patients with homozygous familial hypercholesterolaemia (FH, inherited high cholesterol) are at extremely high risk of premature cardiovascular events due to the burden of elevated LDL cholesterol. Indeed, cardiovascular death at an early age is…

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How do PCSK9-inhibitors reduce lipoprotein(a)?

How do PCSK9-inhibitors reduce lipoprotein(a)?

Beyond lowering LDL cholesterol, PCSK9 inhibition also reduces lipoprotein(a). Prof Derick Raal, University of the Witwatersrand, Johannesburg, South Africa discusses the underlying mechanism. Lipoprotein (a) [Lp(a)] is an LDL-like particle consisting of apolipoprotein(a) [apo(a)] that is disulphide-linked to the apoB moiety of LDL (1). Lp(a)…

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Why PCSK9 inhibitors are needed in FH: SAFEHEART highlights poor LDL cholesterol control

Why PCSK9 inhibitors are needed in FH: SAFEHEART highlights poor LDL cholesterol control

Five-year follow-up data from the Spanish SAFEHEART registry of patients with familial hypercholesterolaemia (FH, inherited high cholesterol) show that attainment of LDL cholesterol is still a major issue. Only 11% attained an LDL-C level of <2.5 mmol/L (100 mg/dl). This was despite increasing maximally tolerated…

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LY3015014: Another PCSK9 monoclonal enters the arena

LY3015014: Another PCSK9 monoclonal enters the arena

Hot on the heels of alirocumab, evolocumab and bococizumab, comes the next PCSK9 monoclonal antibody, LY3015014. In this aaleport, dosing every 4 weeks with LY3015014 resulted in about 50% reduction in LDL cholesterol, comparable to that observed with these other monoclonal antibodies. LY3015014 is a…

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AHA Agenda on FH: Addressing the burden of underdiagnosed and undertreated FH

AHA Agenda on FH: Addressing the burden of underdiagnosed and undertreated FH

Underdiagnosed and undertreated familial hypercholesterolaemia (FH, inherited high cholesterol), is an important contributor to overall coronary heart disease (CHD) death and disability. This issue is clearly highlighted by a study presented at the American Heart Association Scientific Sessions 2015 (1). The investigators used a Markov…

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Stroke risk in heterozygous FH

Stroke risk in heterozygous FH

Are individuals with heterozygous familial hypercholesterolaemia (FH, inherited high cholesterol) at higher risk of stroke? And if so, does statin treatment ameliorate this risk? Results from this meta-analysis suggest this may be the case. Heterozygous FH is undoubtedly associated with an increased risk of premature…

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ODYSSEY 78-week data in heterozygous FH: PCSK9 FORUM Expert view

ODYSSEY 78-week data in heterozygous FH: PCSK9 FORUM Expert view

ESC Congress 2015, 1 September 2015 Familial hypercholesterolaemia (FH, inherited high cholesterol) represents one of the key priorities for PCSK9 monoclonal antibody therapy. This analysis from the ODYSSEY clinical programme with alirocumab, which has the largest group of heterozygous FH patients studied to date, establishes…

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