Evidence mapPaperPMID 24694531Full record

Trial reportJournal of the American College of Cardiology2014

Anti-PCSK9 antibody effectively lowers cholesterol in patients with statin intolerance: the GAUSS-2 randomized, placebo-controlled phase 3 clinical trial of evolocumab.

Erik Stroes, David Colquhoun, David Sullivan, Fernando Civeira, Robert S Rosenson, Gerald F Watts, Eric Bruckert, Leslie Cho, Ricardo Dent, Beat Knusel and 5 more

3 registry-linked trialsOpen access · greenAbstract readClinical Trial, Phase IIIMulticenter StudyRandomized Controlled Trial
PubMed Publisher
In one paragraph

Trial report in Journal of the American College of Cardiology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It reports registered trial NCT01763905. Cited by 208 papers, 21 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
208citing papers in PubMed, 21 pooled it
82.4field-weighted citation impact, top 1% 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.

NCT01763905 phase3completed

A Double-blind, Randomized, Multicenter Study to Evaluate Safety and Efficacy of AMG 145, Compared With Ezetimibe, in Hypercholesterolemic Subjects Unable to Tolerate an Effective Dose of a HMG-CoA Reductase Inhibitor

Ran2013Enrolled307Registered outcomes22Posted comparisons44ConditionsHyperlipidemiaArmsEvolocumab, Ezetimibe, Placebo to Evolocumab, Placebo to Ezetimibe
Open the trial in the graph
NCT04397653 phase4unknown statusnot on this mapstarted 2020, after this paper: background citation

Phase IV Study for Efficacy and Safety of Evolocumab Added to Ezetimibe (Standard of Care) in High Cardiovascular Risk Haemodialized Statin Intolerant Patients With Hypercholesterolemia

TypeinterventionalSponsorPoliclinico Casilino ASL RMBRan2020 to 2020Enrolled50ConditionsHypercholesterolemia, Chronic Kidney Disease Requiring Chronic DialysisArmsEvolocumab, Placebo, Ezetimibe
NCT04659525 phase4unknown statusnot on this mapstarted 2020, after this paper: background citation

Phase IV Study for Efficacy and Safety of Evolocumab Added to Ezetimibe (Standard of Care) in High Cardiovascular Risk Haemodialized Statin Intolerant Patients With Hypercholesterolemia

TypeinterventionalSponsorPoliclinico Casilino ASL RMBRan2020 to 2021Enrolled50ConditionsHypercholesterolemia, CKD Stage 5, Chronic Kidney Disease Requiring Chronic DialysisArmsEvolocumab, Ezetimibe, Placebo
3 · Its place in the literature

Who cites it

208 citing papers in PubMed, 21 syntheses or guidelines pooled it, 526 citations in OpenAlex.

  1. Guideline
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  5. Is a PCSK9 Inhibitor Right for Your Patient? A Review of Treatment Data for Individualized Therapy.International journal of environmental research and public health · 2022
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  8. Biotechnology Approaches for the Treatment of Dyslipidemia.Cardiovascular drugs and therapy · 2021
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  19. A Systematic Review of PCSK9 Inhibitors Alirocumab and Evolocumab.Journal of managed care & specialty pharmacy · 2016
    Pooled it
  20. Pooled it

148 more citing papers are in PubMed but not listed here.

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

15 authors at 9 institutions in 5 countries.

Erik StroesDepartment of Vascular Medicine, Academic Medical Center, Amsterdam, the Netherlands. Electronic address: e.s.stroes@amc.uva.nl.
David ColquhounWesley Medical Centre, Auchenflower, Australia.
David SullivanDepartment of Clinical Biochemistry, Royal Prince Alfred Hospital, Camperdown, Australia.
Fernando CiveiraHospital Universitario Miguel Servet, Zaragoza, Spain.
Robert S RosensonCardiometabolic Disorders Department, Icahn School of Medicine at Mount Sinai, New York, New York.
Gerald F WattsLipid Disorders Clinic, Royal Perth Hospital, School of Medicine and Pharmacology, University of Western Australia, Perth, Australia.
Eric BruckertHopital Pitie-Salpetriere, Paris, France.
Leslie ChoPreventive Cardiology and Rehabilitation, Cleveland Clinic, Cleveland, Ohio.
Ricardo DentAmgen, Thousand Oaks, California.
Beat KnuselAmgen, Thousand Oaks, California.
Allen XueAmgen, Thousand Oaks, California.
Rob ScottAmgen, Thousand Oaks, California.
Scott M WassermanAmgen, Thousand Oaks, California.
Michael RoccoCardiovascular Medicine Department, Cleveland Clinic, Cleveland, Ohio.
GAUSS-2 Investigators
Amgen (United States) · USCleveland Clinic · USAmsterdam UMC Location University of Amsterdam · NLHospital Universitario Miguel Servet · ESIcahn School of Medicine at Mount Sinai · USRoyal Prince Alfred Hospital · AUSorbonne Université · FRThe University of Western Australia · AUWesley Hospital · AU

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

objectivesThis study sought to evaluate the efficacy and safety of subcutaneous evolocumab compared with oral ezetimibe in hypercholesterolemic patients who are unable to tolerate effective statin doses.

backgroundStatin intolerance, which is predominantly due to muscle-related side effects, is reported in up to 10% to 20% of patients. Evolocumab, a fully human monoclonal antibody to proprotein convertase subtilisin/kexin type 9 (PCSK9), demonstrated marked reductions in plasma low-density lipoprotein cholesterol (LDL-C) in a phase 2 study in statin-intolerant patients.

methodsThe GAUSS-2 (Goal Achievement after Utilizing an Anti-PCSK9 Antibody in Statin Intolerant Subjects) trial was a 12-week, double-blind study of randomized patients (2:2:1:1) to evolocumab 140 mg every two weeks (Q2W) or evolocumab 420 mg once monthly (QM) both with daily oral placebo or subcutaneous placebo Q2W or QM both with daily oral ezetimibe 10 mg. Co-primary endpoints were percent change from baseline in LDL-C at the mean of weeks 10 and 12, and at week 12.

resultsThree hundred seven patients (age 62 ± 10 years; LDL-C 193 ± 59 mg/dl) were randomized. Evolocumab reduced LDL-C from baseline by 53% to 56%, corresponding to treatment differences versus ezetimibe of 37% to 39% (p <0.001). Muscle adverse events occurred in 12% of evolocumab-treated patients and 23% of ezetimibe-treated patients. Treatment-emergent adverse events and laboratory abnormalities were comparable across treatment groups.

conclusionsRobust efficacy combined with favorable tolerability makes evolocumab a promising therapy for addressing the largely unmet clinical need in high-risk patients with elevated cholesterol who are statin intolerant. (Goal Achievement After Utilizing an Anti-PCSK9 Antibody in Statin Intolerant Subjects-2; NCT01763905).

Indexed as

AdolescentAdultAgedAntibodies, MonoclonalAntibodies, Monoclonal, HumanizedApoptosisCholesterolDouble-Blind MethodDrug Administration ScheduleDrug Therapy, CombinationDrug ToleranceFemaleFollow-Up StudiesHumansHydroxymethylglutaryl-CoA Reductase InhibitorsHypercholesterolemiaAntibodies, MonoclonalAntibodies, Monoclonal, HumanizedCholesterolevolocumabHydroxymethylglutaryl-CoA Reductase InhibitorsPCSK9 protein, humanProprotein Convertase 9Proprotein ConvertasesSerine EndopeptidasesevolocumabezetimibehypercholesterolemiaLDL-cholesterolstatin intolerance

Identifiers

PMID24694531
OpenAlexW121888607

What Socratic holds

Textmetadata
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 Socratic graph.