News
Do men respond better to PCSK9 inhibition than women?
Accumulating evidence from real-world studies suggests that men may get a greater reduction in LDL-cholesterol (LDL-C) with a PCSK9 inhibitor than women.1,2 However, questions have been raised about whether women are less aggressively treated than men.2 Results of a meta-analysis of six real-world studies with…
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New clues to PCSK9-LDL receptor degradation mechanism
Fresh insights into the molecular mechanism for the degradation of the PCSK9-LDL receptor (LDLR) complex are provided in a new study published in Molecular Metabolism (1). Researchers led by Professor Nabil Seidah (Université de Montréal, Canada) had previously suggested that the M2 subdomain of the C-terminal Cys/His-rich-domain…
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CLEAR OUTCOMES: Topline data show bempedoic acid reduces cardiovascular events
In a press release (1), Esperion announced that the landmark Cholesterol Lowering via Bempedoic acid, an ACL-Inhibiting Regimen (CLEAR) Outcomes trial has met the primary endpoint, with a statistically significant and clinically meaningful reduction in the primary endpoint. This was a 4-part composite of major…
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Lipoprotein(a) and atrial fibrillation – Is there a link?
PCSK9 Forum Co-editors Professors John Chapman and Henry Ginsberg discuss recent data. Atrial fibrillation (AF) is the most common arrhythmia, affecting about 0.5% (circa one in 200) of the worldwide population (1). Moreover, as populations age, prevalence has increased dramatically (2). Due to the associated risk…
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ORION-3: 4-year data with inclisiran
News from the American Heart Association Scientific Sessions 2022 Results from ORION-3, the 4-year open-label extension of the ORION-1 trial (1), showed sustained reduction in LDL cholesterol levels with a favourable safety profile. ORION-1 (ClinicalTrials.gov, NCT02597127) randomized 501 subjects with atherosclerotic cardiovascular disease (ASCVD) or…
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OCEAN(a)-DOSE: Olpasiran shows substantial lipoprotein(a) reduction
News from the American Heart Association Scientific Sessions 2022 In the OCEAN(a)-DOSE trial, treatment with olpasiran, a small interfering RNA (siRNA) agent targeting apolipoprotein(a), reduced lipoprotein(a) [Lp(a)] by up to 100%. The study was simultaneously published in the New England Journal of Medicine (1). In…
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How much reduction of Lp(a) is needed to translate into major clinical benefit? Setting the scene: Focus on PCSK9 inhibitors
Reports from the 17th Virtual Closed Scientific Expert Meeting of the Editorial Board Pia Kamstrup
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EPIC-STEMI: Early alirocumab shows benefit in STEMI patients
EPIC-STEMI (Effects of Acute, Rapid Lowering of Low-Density Lipoprotein Cholesterol with Alirocumab in Patients with ST Segment Elevation Myocardial Infarction Undergoing Primary PCI) showed that starting a PCSK9 inhibitor in the acute setting of STEMI (ST-segment elevation myocardial infarction) provided additional benefit in lowering LDL…
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PCSK9 inhibitors: effects beyond LDL cholesterol lowering
Real-world data from the LIPID-REAL registry show that treatment with a PCSK9 inhibitor was associated with reduction in remnant cholesterol, with greater benefit among patients with higher levels (1). PCSK9 inhibitors are highly efficacious in lowering LDL cholesterol by over 50%, irrespective of baseline lipid…
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FOURIER-OLE: Long-term evolocumab treatment further reduced cardiovascular events
Long-term treatment with evolocumab (on top of intense statin therapy) further reduced cardiovascular events in patients with stable atherosclerotic cardiovascular disease (ASCVD) who previously completed the landmark FOURIER study. Evolocumab treatment was also well tolerated. The results from this open-label extension study (FOURIER-OLE) were published…
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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
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?
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?
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
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?
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
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?
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
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
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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