Evidence map›Paper›PMID 25614280›Full record

ArticleArteriosclerosis, thrombosis, and vascular biology2015

Mipomersen, an antisense oligonucleotide to apolipoprotein B-100, reduces lipoprotein(a) in various populations with hypercholesterolemia: results of 4 phase III trials.

Raul D Santos, Frederick J Raal, Alberico L Catapano, Joseph L Witztum, Elisabeth Steinhagen-Thiessen, Sotirios Tsimikas

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Arteriosclerosis, thrombosis, and vascular biology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 85 papers, 4 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
85citing papers in PubMed, 4 pooled it
20.7field-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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

85 citing papers in PubMed, 4 syntheses or guidelines pooled it, 191 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Guideline
  4. Biotechnology Approaches for the Treatment of Dyslipidemia.Cardiovascular drugs and therapy · 2021
    Pooled it
  5. Trial
  6. Article
  7. RNA-Based Therapies for Inherited Metabolic Disorders.Journal of inherited metabolic disease · 2026
    Review
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  15. Article
  16. Article
  17. Antisense Oligonucleotides in Dyslipidemia Management: A Review of Clinical Trials.High blood pressure & cardiovascular prevention : the official journal of the Italian Society of Hypertension · 2025
    Review
  18. The Impact of Diet on Lipoprotein(a) Levels.Life (Basel, Switzerland) · 2024
    Review
  19. Lipoprotein(a) and cardiovascular disease.The Biochemical journal · 2024
    Review
  20. Review

25 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

6 authors at 2 institutions in 2 countries.

Raul D SantosFrom the Lipid Clinic Heart Institute (InCor), University of São Paulo Medical School Hospital, São Paulo, Brazil (R.D.S.); Carbohydrate and Lipid Metabolism Research Unit, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa (F.J.R.); Department of Pharmacological and Biomolecular Sciences, University of Milan, IRCCS Multimedica, Milan, Italy (A.L.C.); Lipid Ambulatory Clinic, Charite-Universitaetsmedizin Berlin, Berlin, Germany (E.S.-T.); and University of California San Diego, La Jolla (J.L.W., S.T.).
Frederick J RaalFrom the Lipid Clinic Heart Institute (InCor), University of São Paulo Medical School Hospital, São Paulo, Brazil (R.D.S.); Carbohydrate and Lipid Metabolism Research Unit, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa (F.J.R.); Department of Pharmacological and Biomolecular Sciences, University of Milan, IRCCS Multimedica, Milan, Italy (A.L.C.); Lipid Ambulatory Clinic, Charite-Universitaetsmedizin Berlin, Berlin, Germany (E.S.-T.); and University of California San Diego, La Jolla (J.L.W., S.T.).
Alberico L CatapanoFrom the Lipid Clinic Heart Institute (InCor), University of São Paulo Medical School Hospital, São Paulo, Brazil (R.D.S.); Carbohydrate and Lipid Metabolism Research Unit, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa (F.J.R.); Department of Pharmacological and Biomolecular Sciences, University of Milan, IRCCS Multimedica, Milan, Italy (A.L.C.); Lipid Ambulatory Clinic, Charite-Universitaetsmedizin Berlin, Berlin, Germany (E.S.-T.); and University of California San Diego, La Jolla (J.L.W., S.T.).
Joseph L WitztumFrom the Lipid Clinic Heart Institute (InCor), University of São Paulo Medical School Hospital, São Paulo, Brazil (R.D.S.); Carbohydrate and Lipid Metabolism Research Unit, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa (F.J.R.); Department of Pharmacological and Biomolecular Sciences, University of Milan, IRCCS Multimedica, Milan, Italy (A.L.C.); Lipid Ambulatory Clinic, Charite-Universitaetsmedizin Berlin, Berlin, Germany (E.S.-T.); and University of California San Diego, La Jolla (J.L.W., S.T.).
Elisabeth Steinhagen-ThiessenFrom the Lipid Clinic Heart Institute (InCor), University of São Paulo Medical School Hospital, São Paulo, Brazil (R.D.S.); Carbohydrate and Lipid Metabolism Research Unit, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa (F.J.R.); Department of Pharmacological and Biomolecular Sciences, University of Milan, IRCCS Multimedica, Milan, Italy (A.L.C.); Lipid Ambulatory Clinic, Charite-Universitaetsmedizin Berlin, Berlin, Germany (E.S.-T.); and University of California San Diego, La Jolla (J.L.W., S.T.).
Sotirios TsimikasFrom the Lipid Clinic Heart Institute (InCor), University of São Paulo Medical School Hospital, São Paulo, Brazil (R.D.S.); Carbohydrate and Lipid Metabolism Research Unit, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa (F.J.R.); Department of Pharmacological and Biomolecular Sciences, University of Milan, IRCCS Multimedica, Milan, Italy (A.L.C.); Lipid Ambulatory Clinic, Charite-Universitaetsmedizin Berlin, Berlin, Germany (E.S.-T.); and University of California San Diego, La Jolla (J.L.W., S.T.). stsimikas@ucsd.edu.
University of Milan · ITCharité - Universitätsmedizin Berlin · DE

Funding

ROLE OF LIPOXYGENASES IN ATHEROGENESIS IN DIABETES MELLITUSP01HL055798 · NHLBI · UNIVERSITY OF VIRGINIA CHARLOTTESVILLE · PI HEDRICK, CATHERINE C · 1995 to 2016
$28.4M
Transcriptional GenomicsP01HL088093 · NHLBI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI WITZTUM, JOSEPH L. · 2008 to 2018
$26.4M
UC BRAID Center for Accelerated Innovation COVID-19 diagnostic project developmentU54HL119893 · NHLBI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI PALAZZOLO, MICHAEL J · 2013 to 2020
$18.3M
Zebrafish models of vascular inflammation and atherosclerosisR01HL093767 · NHLBI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI MILLER, YURY · 2009 to 2014
$2.5M
Oxidation-specific nanoparticles for imaging atherosclerosisR01HL119828 · NHLBI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI TSIMIKAS, SOTIRIOS · 2013 to 2017
$2.0M
NHLBI NIH HHS P01 HL055798NHLBI NIH HHS P01-HL055798NHLBI NIH HHS P01 HL088093NHLBI NIH HHS P01-HL088093NHLBI NIH HHS R01 HL093767NHLBI NIH HHS R01-HL093767NHLBI NIH HHS R01 HL119828NHLBI NIH HHS R01-HL119828NHLBI NIH HHS U54 HL119893NHLBI NIH HHS U54-HL119893
6 · The paper itself

Abstract

objectiveLp(a) is an independent, causal, genetic risk factor for cardiovascular disease and aortic stenosis. Current pharmacological lipid-lowering therapies do not optimally lower Lp(a), particularly in patients with familial hypercholesterolemia (FH). APPROACH AND

resultsIn 4 phase III trials, 382 patients on maximally tolerated lipid-lowering therapy were randomized 2:1 to weekly subcutaneous mipomersen 200 mg (n=256) or placebo (n=126) for 26 weeks. Populations included homozygous FH, heterozygous FH with concomitant coronary artery disease (CAD), severe hypercholesterolemia, and hypercholesterolemia at high risk for CAD. Lp(a) was measured 8× between baseline and week 28 inclusive. Of the 382 patients, 57% and 44% had baseline Lp(a) levels >30 and >50 mg/dL, respectively. In the pooled analysis, the mean percent decrease (median, interquartile range in Lp(a) at 28 weeks was significantly greater in the mipomersen group compared with placebo (-26.4 [-42.8, -5.4] versus -0.0 [-10.7, 15.3]; P<0.001). In the mipomersen group in patients with Lp(a) levels >30 or >50 mg/dL, attainment of Lp(a) values ≤30 or ≤50 mg/dL was most frequent in homozygous FH and severe hypercholesterolemia patients. In the combined groups, modest correlations were present between percent change in apolipoprotein B-100 and Lp(a) (r=0.43; P<0.001) and low-density lipoprotein cholesterol and Lp(a) (r=0.36; P<0.001) plasma levels.

conclusionsMipomersen consistently and effectively reduced Lp(a) levels in patients with a variety of lipid abnormalities and cardiovascular risk. Modest correlations were present between apolipoprotein B-100 and Lp(a) lowering but the mechanistic relevance mediating Lp(a) reduction is currently unknown.

Indexed as

AdultAgedAnticholesteremic AgentsApolipoprotein B-100BiomarkersCardiovascular DiseasesClinical Trials, Phase III as TopicDown-RegulationFemaleHumansHyperlipoproteinemia Type IILipoprotein(a)MaleMiddle AgedOligodeoxyribonucleotides, AntisenseOligonucleotidesAnticholesteremic AgentsAPOB protein, humanApolipoprotein B-100BiomarkersLipoprotein(a)mipomersenOligodeoxyribonucleotides, AntisenseOligonucleotidesantisense oligonucleotidecoronary artery diseasedyslipidemiashyperlipoproteinemia type IIhypolipidemic agents

Identifiers

PMID25614280
PMCPMC4344404
OpenAlexW2106951652

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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.