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Reducing residual risk: Are cholesterol crystals the next target?

Reducing residual risk: Are cholesterol crystals the next target?

Professor John Chapman  Sorbonne University, Pitié-Salpetrière University Hospital, National Institute for Health and Medical Research (INSERM), Paris France Cardiovascular disease is the worldwide leading cause of mortality, responsible for about one-third of all deaths (1). Much of this burden is attributable to atherosclerotic cardiovascular disease…

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Trial with CRISPR PCSK9 treatment underway

Trial with CRISPR PCSK9 treatment underway

The first trial of VERVE-101, a novel gene editing treatment that permanently turns off the PCSK9 gene in the liver to lower LDL cholesterol, is now underway in New Zealand (NCT05398029)(1). The trial is recruiting patients with heterozygous familial hypercholesterolaemia (FH) caused by an LDLR…

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Do PCSK9 inhibitors have a role in sepsis?

Do PCSK9 inhibitors have a role in sepsis?

Sepsis poses a major global burden affecting over 50 million people and contributing to over 11 million deaths (2017 data) (1). Even among people who survive, many endure substantial reduction in physical, emotional and cognitive quality of life. Current management strategies focus on early aggressive…

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RACING trial: Do we need to rethink LDL-lowering strategies in Asian high-risk patients?

RACING trial: Do we need to rethink LDL-lowering strategies in Asian high-risk patients?

Guidelines recommend maximal tolerable statin therapy as the foundation of LDL cholesterol lowering in patients with atherosclerotic cardiovascular disease (ASCVD), ideally in combination with non-statin therapeutic options (1,2). While this strategy is undoubtedly effective, there may be concerns regarding possible side effects with high-intensity statin…

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More reassurance on the safety of PCSK9 inhibitors

More reassurance on the safety of PCSK9 inhibitors

The latest analysis of the Food and Drug Administration’s adverse event reporting system (FAERS) reinforced the safety of alirocumab and evolocumab. The FAERS is a database containing information on adverse event and medication error reports submitted to the Food and Drug Administration, which supports post-marketing…

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Circulating PCSK9 in children: A potential marker of cardiovascular risk?

Circulating PCSK9 in children: A potential marker of cardiovascular risk?

Results from a study in Lebanese school children show an association between circulating PCSK9 levels and plasma concentration of total, LDL and non-HDL cholesterol, suggesting that measuring PCSK9 levels may have potential as a predictor of cardiovascular risk. Dyslipidaemia is highly prevalent in Lebanon among…

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More insights from ODYSSEY OUTCOMES

More insights from ODYSSEY OUTCOMES

Greatest absolute benefit from PCSK9 inhibition in highest risk patients Two recent analyses from ODYSSEY OUTCOMES show that acute coronary syndrome (ACS) patients at highest risk, including those with a history of recurrent cardiovascular events, or with several metabolic risk factors, gain the most absolute…

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ODYSSEY OUTCOMES analysis: A case for first-line use of statin-PCSK9 inhibitor in ACS?

ODYSSEY OUTCOMES analysis: A case for first-line use of statin-PCSK9 inhibitor in ACS?

In this latest analysis from ODYSSEY OUTCOMES, combination treatment with alirocumab on top of optimised statin therapy allowed >90% of acute coronary syndrome (ACS) patients to achieve guideline-recommended LDL cholesterol goals, far greater than that anticipated with ezetimibe. The 2019 European Society of Cardiology/European Atherosclerosis…

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Real-world use of PCSK9 inhibitors: latest insights

Real-world use of PCSK9 inhibitors: latest insights

News from the European Atherosclerosis Society 90th Congress, 22-25 May 2022, Milan, Italy Alirocumab or evolocumab showed a comparable efficacy and safety profile as that reported in clinical trials, according to a meta-analysis of over 28,000 patients prescribed either PCSK9 inhibitor in a real-world clinical…

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EAS FH Studies Collaboration: missed opportunities to identify FH early

EAS FH Studies Collaboration: missed opportunities to identify FH early

News from the European Atherosclerosis Society 90th Congress, 22-25 May 2022, Milan, Italy Familial hypercholesterolaemia (FH) is characterised by high cholesterol levels from birth, which if untreated confer a risk of accelerated atherosclerotic cardiovascular disease (1). Early identification of children with FH and initiation of…

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Why combination LDL-lowering therapy is mandated by guidelines for very high-risk patients: insights from DA VINCI

Why combination LDL-lowering therapy is mandated by guidelines for very high-risk patients: insights from DA VINCI

News from the European Atherosclerosis Society 90th Congress, 22-25 May 2022, Milan, Italy According to a simulation study using the DA VINCI data (1), combination LDL-lowering therapy including a PCSK9 inhibitor would result in ~90% of very high-risk patients achieving LDL cholesterol goal, as defined…

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ETESIAN: Phase 2b trial of PCSK9 antisense oligonucleotide

ETESIAN: Phase 2b trial of PCSK9 antisense oligonucleotide

News from the European Atherosclerosis Society 90th Congress, 22-25 May 2022, Milan, Italy In this study, AZD8233 (ION 449) reduced LDL cholesterol by over 70% on top of statin in patients with dyslipidaemia. The findings follow an initial report at the American College of Cardiology…

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News from ACC.22 – New insights from ORION-10 and ORION-11: inclisiran effective in post-MI patients

News from ACC.22 – New insights from ORION-10 and ORION-11: inclisiran effective in post-MI patients

Inclisiran was effective in lowering LDL cholesterol and generally well tolerated in patients with a prior myocardial infarction (MI), irrespective of the timing of MI, according to latest data from the ORION-10 and ORION-11 studies. Inclisiran is a small interfering ribonucleic acid (siRNA) therapeutic targeting…

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News from ACC.22 late breaking trials: Results from the APOLLO trial with new RNA therapeutic

News from ACC.22 late breaking trials: Results from the APOLLO trial with new RNA therapeutic

Results from the APOLLO trial showed that single doses of SLN360, an investigational short interfering RNA (siRNA), resulted in dose-dependent lowering of plasma lipoprotein(a) [Lp(a)] concentration in adults with high Lp(a) and no pre-existing cardiovascular disease. The trial was simultaneously published in the Journal of…

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News from ACC.22 – Long-term data from HAUSER-OLE in paediatric familial hypercholesterolaemia

News from ACC.22 – Long-term data from HAUSER-OLE in paediatric familial hypercholesterolaemia

Results from the HAUSER Open-Label Extension Study (HAUSER-OLE) (1) show that treatment with evolocumab was well tolerated, safe, and led to substantial reduction in LDL cholesterol in children with heterozygous familial hypercholesterolaemia (FH). As previously reported on PCSK9 Forum, HAUSER-RCT evaluated the efficacy and safety…

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News from ACC.22 late breaking trials: PACMAN-AMI delivers

News from ACC.22 late breaking trials: PACMAN-AMI delivers

Results from the PACMAN-AMI (Effects of the PCSK9 Antibody Alirocumab on Coronary Atherosclerosis in Patients With Acute Myocardial Infarction) trial using multimodality coronary imaging demonstrate the benefit of starting intensive lipid lowering in the acute setting of acute myocardial infarction (AMI). PCSK9 inhibition on top…

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Consider familial hypercholesterolaemia in young heart attack survivors

Consider familial hypercholesterolaemia in young heart attack survivors

Familial hypercholesterolaemia (FH) was more than 30-fold more prevalent among young people surviving an acute coronary syndrome (ACS) compared with the general population, according to this French report. These findings reinforce the need to investigate the possibility of FH in these individuals. Heterozygous FH is…

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Lessons from the HEYMANS registry: do we need to lower LDL thresholds for initiating a PCSK9 inhibitor?

Lessons from the HEYMANS registry: do we need to lower LDL thresholds for initiating a PCSK9 inhibitor?

Insights from the HEYMANS registry show that criteria for initiation of the PCSK9 inhibitor in real-world practice are far from optimal. The 2019 European Society of Cardiology/European Atherosclerosis Society (ESC/EAS) guidelines for management of dyslipidaemia underline the need for combination therapy in high-risk individuals to…

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New trials: Inclisiran investigated in adolescents with familial hypercholesterolaemia

New trials: Inclisiran investigated in adolescents with familial hypercholesterolaemia

Trials of PCSK9-targeted therapies have predominantly focused on adults at increased cardiovascular risk due to elevated LDL cholesterol levels. In the setting of familial hypercholesterolaemia (FH), in which individuals have elevated LDL cholesterol levels from birth, it makes sense to prioritize initiation of treatment in…

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Update from FOURIER: Evolocumab provides benefit in patients with prior PCI

Update from FOURIER: Evolocumab provides benefit in patients with prior PCI

In this latest analysis from FOURIER (Further Cardiovascular Outcomes Research With PCSK9 Inhibition in Subjects With Elevated Risk) (1), evolocumab treatment was associated with significant clinical benefit in patients with prior percutaneous coronary intervention (PCI), who are at high residual risk for multiple types of…

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