News
Does PCSK9 inhibition have effects beyond lipid lowering?
While retention of LDL within the arterial wall is critical in the initiation of atherosclerosis (1), the immune/inflammatory component should not be discounted. Indeed, migration of monocytes into the arterial wall contributes to arterial inflammation and atherosclerosis progression. This might suggest that intensive reduction of…
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Cardiovascular risk in familial hypercholesterolaemia: Consider also the presence of subclinical disease
Inclusion of ultrasound evaluation for carotid plaques may have relevance in assessment of cardiovascular risk in familial hypercholesterolemia (FH, inherited high cholesterol) beyond LDL cholesterol and family history of premature coronary heart disease, according to this Italian study. In total, the study included 263 patients…
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How many familial hypercholesterolemia patients are eligible for PCSK9 inhibition?
Familial hypercholesterolemia (FH, inherited high cholesterol) is a high cardiovascular risk condition. Despite this, the extent of undertreatment is well recognized, with less than one in 5 patients attaining LDL cholesterol goal on maximally tolerated statin plus ezetimibe therapy (1). With the availability of PCSK9…
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ADA 2017: Alirocumab shows benefit in diabetes patients
Data from the ODYSSEY trials, including a pooled analysis of nearly 1,000 patients, reported at the American Diabetes Association (ADA) 2017 Scientific Sessions showed that alirocumab was effective in type 1 and 2 diabetes patients, including those with mixed dyslipidaemia, with no impact on HbA1c….
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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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ODYSSEY-DM-INSULIN: alirocumab in type 1 and 2 diabetes
This phase III study is addressing unanswered questions relating to the efficacy of the PCSK9 inhibition in insulin-treated patients with type 1 or type 2 diabetes and high cardiovascular risk. Briefly, this randomized, double-blind, placebo-controlled, multicentre study plans to enrol 400 patients with type 2…
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No increase in dementia risk with low LDL cholesterol levels due to genetic variants
There has been controversy regarding a possible link between low LDL cholesterol levels and risk for neurological disease given that cholesterol is a major constituent of the myelin encircling neurons in the brain. The results of this Mendelian randomization study, however, refutes an association between…
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Statin intolerance – 50% higher risk of recurrent heart attack in statin intolerant patients
Debated in the literature (1-3), statin intolerance is very much a hot topic at the moment. This new report highlights the detrimental effects on cardiovascular outcome in patients with statin intolerance. Statin-associated muscle symptoms (SAMS) are the most common clinical manifestation of statin intolerance. The…
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Dr Peter Lansberg: What does FOURIER mean for FH patients?
PCSK9 Forum News Editor, Dr Peter Lansberg (Academic Medical Center, Amsterdam, the Netherlands) discusses what the landmark results of FOURIER and SPIRE-2 will mean for the management of patients with familial hypercholesterolaemia (FH, inherited high cholesterol). SPIRE-2 is clearly relevant given that this study also…
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Evinacumab, ANGPTL3 inhibitor, awarded breakthrough status by FDA
This monoclonal antibody to angiopoietin-like protein 3 (ANGPTL3), an inhibitor of lipoprotein lipase and endothelial lipase, is targeted to homozygous familial hypercholesterolaemia (FH, inherited high cholesterol), the most severe form of FH. The award of breakthrough status by the Food and Drugs Administration reflects the…
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Dr Brian Ference sets the record straight on questions about benefit in FOURIER
In discussions at ACC.2017, some have suggested that the results of FOURIER were less than anticipated from the meta-analysis of statin trials by the Cholesterol Treatment Trialists’ Collaboration (CTTC) (1). PCSK9 Forum Editor Dr Brian Ference (Division of Cardiovascular Medicine, Wayne State University School of…
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Events are the driver in PCSK9 cardiovascular outcomes trials
A recurrent question at ACC.2017 was why FOURIER had a short duration of follow-up, given the average duration of the statin trials was typically in the region of 4-5 years. This debate has been fanned by colourful but misinformed reports in the investment media (1).’…
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SPIRE trials: Bococizumab was insufficiently humanized for long-term use
The development of bococizumab, the third of the PCSK9 monoclonal antibodies, was discontinued by Pfizer in early November (1). Insights from a late breaker trial presentation provide some answers why this might be the case. SPIRE programme: lipid lowering trials The SPIRE program included 6…
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SPIRE-2: Cardiovascular benefit in very high risk patients
Evidence from the two cardiovascular outcomes studies with bococizumab, notably SPIRE-2, added to the buzz around FOURIER. According to PCSK9 Forum Editor Professor Philip Barter (University of New South Wales, Sydney, Australia): ‘Despite follow-up being short due to termination of the development of bococizumab, SPIRE-2…
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A landmark day for PCSK9 inhibition
What a landmark day for lipid lowering. All eyes were focused on FOURIER at the first of the late-breaking clinical trial sessions at ACC.2017. And the results didn’t disappoint. In patients with stable cardiovascular disease on maximally tolerated statin therapy, evolocumab treatment lowered LDL cholesterol…
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Countdown to FOURIER: What are the implications for patients?
Countdown to FOURIER: What are the implications for patients? PCSK9 Forum Editor Professor Anthony Wierzbicki gives his view.
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Countdown to FOURIER: Are very low levels of LDL cholesterol safe?
A view from PCSK9 Forum Editor Dr Peter Lansberg (Academic Medical Center, Amsterdam, the Netherlands) Comment relates to: Giugliano RP, Wiviott SD, Blazing MA et al. Long-term Safety and Efficacy of Achieving Very Low Levels of Low-Density Lipoprotein Cholesterol A Prespecified Analysis of the IMPROVE-IT…
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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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Cumulative 4-year OSLER data look good, sustained LDL lowering
In this report from OSLER (Open-Label Study of Long-term Evaluation Against LDL-C), covering the longest exposure to PCSK9 inhibitors to date, there was no decrease in the LDL cholesterol lowering response to evolocumab treatment over time, and no signal for any increase in adverse events….
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Looking to FOURIER: What do the trials tell us about LDL lowering and cardiovascular events?
Presentation of full results from the FOURIER cardiovascular outcomes trial with the PCSK9 monoclonal antibody evolocumab is imminent. Here, PCSK9 Forum Editor Professor Anthony Wierzbicki (Guy’s and St Thomas’ NHS Foundation Trust, London UK) looks back over more than 25 years of trials of LDL…
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