MétaCan
Menu
Back to cohort
Record W3082704660 · doi:10.1016/j.jacl.2020.08.009

Bempedoic acid safety analysis: Pooled data from four phase 3 clinical trials

2020· article· en· W3082704660 on OpenAlexafffund
Harold Bays, Maciej Banach, Alberico L. Catapano, P. Barton Duell, Antonio M. Gotto, Ulrich Laufs, Lawrence A. Leiter, G.B. John Mancini, Kausik K. Ray, LeAnne T. Bloedon, William J. Sasiela, Zhan Ye, Christie M. Ballantyne

Bibliographic record

VenueJournal of clinical lipidology · 2020
Typearticle
Languageen
FieldMedicine
TopicLipoproteins and Cardiovascular Health
Canadian institutionsUniversity of British ColumbiaUniversity of TorontoSt. Michael's Hospital
FundersAbbott VascularNational Institutes of HealthNovo NordiskMedicines CompanyValeant Pharmaceuticals InternationalNovartisEli Lilly and CompanyAstraZenecaPfizerNIHR Imperial Biomedical Research CentreAmgenBoehringer IngelheimKowa CompanyMeso Scale DiagnosticsSanofiEsperion TherapeuticsMerckAmerican Heart AssociationAmerican Diabetes Association
KeywordsMedicinePlaceboInternal medicineDiscontinuationGastroenterologyAdverse effectmyalgiaUric acid

Abstract

fetched live from OpenAlex

BACKGROUND: An ongoing need exists for safe and effective lipid-lowering therapies (LLTs) for patients unable to achieve desired lipid levels with current treatment options. OBJECTIVE: The objective of this study was to describe the safety profile of bempedoic acid, an oral, first-in-class, adenosine triphosphate (ATP)-citrate lyase inhibitor that significantly reduces low-density lipoprotein cholesterol (LDL-C) levels by 17.4%-28.5% vs placebo. METHODS: This was a pooled analysis of four phase 3, randomized (2:1), double-blind, placebo-controlled studies in patients with hypercholesterolemia who required additional LDL-C lowering, despite stable maximally-tolerated LLT. Patients received 180 mg of bempedoic acid (n = 2424) or placebo (n = 1197) once daily for 12 to 52 weeks. Assessments included treatment-emergent adverse events (TEAEs) and clinical laboratory tests. RESULTS: Of 3621 patients (the median drug exposure: 363 days), exposure-adjusted TEAE rates were 87.1/100 and 82.9/100 person-years (PY) for bempedoic acid and placebo, respectively. No single TEAE influenced the difference in rates. TEAEs leading to discontinuation occurred at rates of 13.4/100 and 8.9/100 PY for bempedoic acid vs placebo, with the most common cause being myalgia, which occurred less frequently with bempedoic acid vs placebo (1.5/100 vs 2.0/100 PY). Rates of myalgia and muscle weakness were comparable vs placebo. Bempedoic acid was associated with mild increases in blood urea nitrogen, creatinine, and uric acid and decreases in hemoglobin. These laboratory abnormalities were apparent by week 4, stable over time, and reversible after treatment cessation. Gout incidence was 1.6/100 vs 0.5/100 PY in the bempedoic acid vs placebo groups. New-onset diabetes/hyperglycemia occurred less frequently with bempedoic acid vs placebo (4.7/100 vs 6.4/100 PY). The safety profile was consistent across subgroups. CONCLUSIONS: Bempedoic acid is generally safe and well tolerated among patients with hypercholesterolemia who require additional LLT.

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)0.020
metaresearch head score (Gemma)0.016
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Meta-analysis · Consensus signal: none
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.020
Threshold uncertainty score0.107

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0200.016
Meta-epidemiology (narrow)0.0030.001
Meta-epidemiology (broad)0.0090.012
Bibliometrics0.0020.002
Science and technology studies0.0010.001
Scholarly communication0.0020.002
Open science0.0010.001
Research integrity0.0020.003
Insufficient payload (model declined to judge)0.0030.001

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 head0.549
GPT teacher head0.566
Teacher spread0.016 · 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 designMeta-analysis
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".

Quick stats

Citations102
Published2020
Admission routes2
Has abstractno

Explore more

Same venueJournal of clinical lipidologySame topicLipoproteins and Cardiovascular HealthFrench-language works237,207