Evidence map›Paper›PMID 37954898›Full record

ArticleCritical care explorations2023

Pharmacologic and Genetic Downregulation of Proprotein Convertase Subtilisin/Kexin Type 9 and Survival From Sepsis.

Patrick R Lawler, Garen Manvelian, Alida Coppi, Amy Damask, Michael N Cantor, Manuel A R Ferreira, Charles Paulding, Nilanjana Banerjee, Dadong Li, Susan Jorgensen and 30 more

Registry-linked trialOpen access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Critical care explorations, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It reports registered trial NCT01663402. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
0.2field-weighted citation impact, top 39% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT01663402 phase3completed

A Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Study to Evaluate the Effect of Alirocumab (SAR236553/REGN727) on the Occurrence of Cardiovascular Events in Patients Who Have Recently Experienced an Acute Coronary Syndrome

Ran2012Enrolled18,924Registered outcomes15Posted comparisons6ConditionsAtherosclerotic Cardiovascular DiseaseArmsAlirocumab, LMT, Placebo
Open the trial in the graph
3 · Its place in the literature

Who cites it

0 citing papers in PubMed, 1 citations in OpenAlex.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

40 authors at 15 institutions in 7 countries.

Patrick R LawlerDepartment of Medicine, McGill University Health Centre, McGill University, Montreal, QC, Canada.
Garen ManvelianRegeneron Pharmaceuticals, Inc., Tarrytown, NY.
Alida CoppiRegeneron Pharmaceuticals, Inc., Tarrytown, NY.
Amy DamaskRegeneron Genetics Center, Tarrytown, NY.
Michael N CantorRegeneron Genetics Center, Tarrytown, NY.
Manuel A R FerreiraRegeneron Genetics Center, Tarrytown, NY.
Charles PauldingRegeneron Genetics Center, Tarrytown, NY.
Nilanjana BanerjeeRegeneron Genetics Center, Tarrytown, NY.
Dadong LiRegeneron Genetics Center, Tarrytown, NY.
Susan JorgensenRegeneron Pharmaceuticals, Inc., Tarrytown, NY.
Richa AttreRegeneron Pharmaceuticals, Inc., Tarrytown, NY.
David J CareyDepartment of Molecular and Functional Genomics, Geisinger Medical Center, Danville, PA.
Kristi KrebsEstonian Genome Centre, Institute of Genomics, University of Tartu, Tartu, Estonia.
Lili MilaniEstonian Genome Centre, Institute of Genomics, University of Tartu, Tartu, Estonia.
Kristian HveemK.G. Jebsen Center for Genetic Epidemiology, Department of Public Health and Nursing, NTNU, Norwegian University of Science and Technology, Trondheim, Norway.
Jan K DamåsGemini Center for Sepsis Research, Department of Circulation and Medical Imaging, NTNU, Norwegian University of Science and Technology, Trondheim, Norway.
Erik SolligårdGemini Center for Sepsis Research, Department of Circulation and Medical Imaging, NTNU, Norwegian University of Science and Technology, Trondheim, Norway.
Stefan StenderDepartment of Clinical Biochemistry, Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark.
Anne Tybjærg-HansenDepartment of Clinical Biochemistry, Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark.
Børge G NordestgaardDepartment of Clinical Biochemistry, Copenhagen University Hospital - Herlev Gentofte, University of Copenhagen, Copenhagen, Denmark.
Tamara Hernandez-BeeftinkResearch Unit, Hospital Universitario N.S. de Candelaria, Universidad de La Laguna, Santa Cruz de Tenerife, Spain.
Tormod RogneGemini Center for Sepsis Research, Department of Circulation and Medical Imaging, NTNU, Norwegian University of Science and Technology, Trondheim, Norway.
Carlos FloresResearch Unit, Hospital Universitario N.S. de Candelaria, Universidad de La Laguna, Santa Cruz de Tenerife, Spain.
Jesús VillarResearch Unit, Hospital Universitario de Gran Canaria Dr. Negrin, Las Palmas de Gran Canaria, Spain.
Keith R WalleyCentre for Heart Lung Innovation, University of British Columbia, Vancouver, BC, Canada.
Vincent X LiuKaiser Permanente Northern California, Division of Research, Oakland, CA.
Alison E FohnerKaiser Permanente Northern California, Division of Research, Oakland, CA.
Luca A LottaRegeneron Genetics Center, Tarrytown, NY.
Christos A KyratsousRegeneron Pharmaceuticals, Inc., Tarrytown, NY.
Mark W SleemanRegeneron Pharmaceuticals, Inc., Tarrytown, NY.
Michel ScemamaSanofi, Chilly-Mazarin, France.
Richard DelGizziRegeneron Pharmaceuticals, Inc., Tarrytown, NY.
Robert PordyRegeneron Pharmaceuticals, Inc., Tarrytown, NY.
Julie E HorowitzRegeneron Genetics Center, Tarrytown, NY.
Aris BarasRegeneron Pharmaceuticals, Inc., Tarrytown, NY.
Greg S MartinPulmonary, Allergy, Critical Care and Sleep Medicine, Emory University, Atlanta, GA.
Philippe Gabriel StegUniversité de Paris, INSERM U-1148 F75018 Paris, France and Assistance Publique-Hôpitaux de Paris, Paris, France.
Gregory G SchwartzDivision of Cardiology, University of Colorado School of Medicine, Aurora, CA.
Michael SzarekDivision of Cardiology, University of Colorado School of Medicine, Aurora, CA.
Shaun G GoodmanDivision of Cardiology, Department of Medicine, University of Toronto, Toronto, ON, Canada.
Regeneron (United States) · USNorwegian University of Science and Technology · NOKaiser Permanente · USUniversity of Tartu · EECopenhagen University Hospital · DKEmory University · USHospital Universitario de Gran Canaria Doctor Negrín · ESInstituto de Salud Carlos III · ESRigshospitalet · DKSanofi (France) · FRSUNY Downstate Health Sciences University · USUniversidad de La Laguna · ESUniversity of Alberta · CAUniversity of British Columbia · CAUniversity of Toronto · CA

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

objectivesTreatments that prevent sepsis complications are needed. Circulating lipid and protein assemblies-lipoproteins play critical roles in clearing pathogens from the bloodstream. We investigated whether early inhibition of proprotein convertase subtilisin/kexin type 9 (PCSK9) may accelerate bloodstream clearance of immunogenic bacterial lipids and improve sepsis outcomes.

designGenetic and clinical epidemiology, and experimental models.

settingHuman genetics cohorts, secondary analysis of a phase 3 randomized clinical trial enrolling patients with cardiovascular disease (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab [ODYSSEY OUTCOMES]; NCT01663402), and experimental murine models of sepsis. PATIENTS OR SUBJECTS: Nine human cohorts with sepsis (total

interventionsObservational human cohort studies used genetic MEASUREMENTS AND MAIN

resultsAcross human cohort studies, the effect estimate for 28-day mortality after sepsis diagnosis associated with genetic

conclusionsPCSK9 inhibition may improve clinical outcomes in sepsis in preventive, pretreatment settings.

Indexed as

endotoxinslipid regulating agentsproprotein convertase subtilisin/kexin type 9sepsisseptic shock

Identifiers

PMID37954898
PMCPMC10635596
OpenAlexW4388501064

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.