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Abstract 14267: Evinacumab Lowers LDL-C in Patients With Homozygous Familial Hypercholesterolemia Irrespective of Background Lipid-lowering Medication

2020· article· en· W3103690900 on OpenAlexaff
Frederick J. Raal, Robert S. Rosenson, Laurens F. Reeskamp, G. Kees Hovingh, John J.P. Kastelein, Paolo Rubba, Shazia Ali, Poulabi Banerjee, Kuo‐Chen Chan, Nagwa Khilla, Jennifer McGinniss, Robert Pordy, Yi Zhang, Daniel Gaudet

Bibliographic record

VenueCirculation · 2020
Typearticle
Languageen
FieldMedicine
TopicLipid metabolism and disorders
Canadian institutionsUniversité de MontréalUniversité du Québec à Chicoutimi
Fundersnot available
KeywordsMedicineEzetimibePCSK9Familial hypercholesterolemiaPlaceboInternal medicineStatinAlirocumabClinical endpointGastroenterologyRandomized controlled trialCholesterolLipoproteinLDL receptor

Abstract

fetched live from OpenAlex

Background: Homozygous familial hypercholesterolemia (HoFH) is characterized by very premature atherosclerotic cardiovascular disease due to profoundly elevated levels of LDL-C. Attempts to lower LDL-C in patients with HoFH often require multiple lipid-lowering medications (LLMs). Evinacumab, an angiopoietin-like protein 3 inhibitor, has been shown to reduce LDL-C in patients with HoFH by approximately 50% when added to maximally tolerated background LLMs. Objective: In this post-hoc analysis we assessed efficacy of evinacumab in patients with HoFH according to background LLM type. Methods: This was a double-blind, placebo-controlled, 24-week phase 3 trial (NCT03399786) that randomized patients 2:1 to receive intravenous (IV) evinacumab 15 mg/kg (n=43) or IV placebo (n=22) every 4 weeks. The effect of background LLMs on the efficacy of evinacumab to lower LDL-C was assessed for the following subgroups: high intensity-statin, low-intensity statins, lomitapide, triple therapy (ezetimibe + PCSK9 inhibitor + statin), and quadruple therapy (triple therapy + lomitapide). Primary endpoint was % LDL-C reduction from baseline to week 24. Results: At baseline, 55.4% (evinacumab, 58.1%; placebo, 50.0%) of HoFH patients were on triple therapy. Overall, 93.8% were on statins (76.9% on high intensity statins). Across LLM subgroups, mean baseline LDL-C levels ranged from 166.8 mg/dL to 281.8 mg/dL (Table). From baseline to week 24, marked reductions in LDL-C occurred with evinacumab treatment, which were observed in all groups: quadruple therapy (66.8%), triple therapy (56.0%), lomitapide (49.6%), high-intensity statins (48.6%) and low-intensity statins (41.0%). Evinacumab was generally well-tolerated. Conclusions: Evinacumab substantially lowers LDL-C levels in patients with HoFH irrespective of background LLM.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame machine prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.

metaresearch head score (Codex)0.001
metaresearch head score (Gemma)0.001
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: none
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.005
Threshold uncertainty score0.016

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0010.001
Meta-epidemiology (narrow)0.0010.000
Meta-epidemiology (broad)0.0020.001
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0010.000
Open science0.0000.000
Research integrity0.0010.001
Insufficient payload (model declined to judge)0.0050.001

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.019
GPT teacher head0.250
Teacher spread0.231 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designObservational
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

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Citations2
Published2020
Admission routes1
Has abstractyes

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