CoChat
Sign Up
Cited by 1,094Lipoproteins and Cardiovascular HealthLipid metabolism and disordersCholesterol and Lipid Metabolism

The DOI matches its Crossref record; 28 of the 28 references it cites were found in a registry or an index.

Lipoprotein(a) Reduction in Persons with Cardiovascular Disease

Open access
Tsimikas, Sotirios, Karwatowska-Prokopczuk, Ewa, Gouni-Berthold, Ioanna, Tardif, Jean-Claude, Baum, Seth J., Steinhagen-Thiessen, Elizabeth, Shapiro, Michael D., Stroes, Erik S., Moriarty, Patrick M., Nordestgaard, Børge G., Xia, Shuting, Guerriero, Jonathan, Viney, Nicholas J., O’Dea, Louis, Witztum, Joseph L.·2020·New England Journal of Medicine
DOI 10.1056/nejmoa1905239
Open this paper in CoChat — free accountOpen PDF

Abstract

BACKGROUNDLipoprotein(a) levels are genetically determined and, when elevated, are a risk factor for cardiovascular disease and aortic stenosis.There are no approved pharmacologic therapies to lower lipoprotein(a) levels. METHODSWe conducted a randomized, double-blind, placebo-controlled, dose-ranging trial involving 286 patients with established cardiovascular disease and screening lipoprotein(a) levels of at least 60 mg per deciliter (150 nmol per liter).Patients received the hepatocyte-directed antisense oligonucleotide AKCEA-APO(a)-L Rx , referred to here as APO(a)-L Rx (20, 40, or 60 mg every 4 weeks; 20 mg every 2 weeks; or 20 mg every week), or saline placebo subcutaneously for 6 to 12 months.The lipoprotein(a) level was measured with an isoform-independent assay.The primary end point was the percent change in lipoprotein(a) level from baseline to month 6 of exposure (week 25 in the groups that received monthly doses and week 27 in the groups that received more frequent doses). RESULTSThe median baseline lipoprotein(a) levels in the six groups ranged from 204.5 to 246.6 nmol per liter.Administration of APO(a)-L Rx resulted in dose-dependent decreases in lipoprotein(a) levels, with mean percent decreases of 35% at a dose of 20 mg every 4 weeks, 56% at 40 mg every 4 weeks, 58% at 20 mg every 2 weeks, 72% at 60 mg every 4 weeks, and 80% at 20 mg every week, as compared with 6% with placebo (P values for the comparison with placebo ranged from 0.003 to <0.001).There were no significant differences between any APO(a)-L Rx dose and placebo with respect to platelet counts, liver and renal measures, or influenza-like symptoms.The most common adverse events were injection-site reactions.CONCLUSIONS APO(a)-L Rx reduced lipoprotein(a) levels in a dose-dependent manner in patients who had elevated lipoprotein(a) levels and established cardiovascular disease.

Overview

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1056/nejmoa1905239

Cites

28 of 28 references verified0 citation errors · 0 not checkable

Statistics

Verification

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Citations

Cites

Flagged first, then by citations

Show all 28 references

Cited by

Sorted by citations

Items 901–1,000 of 1,001

Related

See all

Metadata

Authors
Tsimikas, S., Karwatowska-Prokopczuk, E., Gouni-Berthold, I., Tardif, J.-C., Baum, S. J., Steinhagen-Thiessen, E., Shapiro, M. D., Stroes, E. S., Moriarty, P. M., Nordestgaard, B. G., Xia, S., Guerriero, J., Viney, N. J., O’Dea, L., & Witztum, J. L.
Affiliations
  • University of Cologne (DE)
  • From the Divisions of Cardiovascular Medicine (S.T.) and Endocrinology and Metabolism (J.L.W.), University of California, San Diego, La Jolla, and Ionis Pharmaceuticals, Carlsbad (S.T., S.X., N.J.V.) — both in California; Akcea Therapeutics, Boston (E.K.-P., J.G., L.O.); Polyclinic for Endocrinology, Diabetes and Preventive Medicine, University of Cologne, Cologne, Germany (I.G.-B.); Montreal Heart Institute, Université de Montréal, Montreal (J.-C.T.); Excel Medical Clinical Trials, Boca Raton, FL ...
  • Oregon Health & Science University (US)
  • University of Copenhagen (DK)
ORCID
Venue
New England Journal of Medicine
Publisher
Massachusetts Medical Society
Published
2020-01-16
Volume
382
Issue
3
Pages
244-255
ISSN
  • 0028-4793 (ISSN-L)
  • 1533-4406
DOI
10.1056/nejmoa1905239
OpenAlex
W2997944188
Semantic Scholar
725c405ccc1ec3726f9ba922da158107891d134f
Cited by
1,094
References
28
Citations by year
2026: 204 · 2025: 176 · 2024: 156 · 2023: 149 · 2022: 159 · 2021: 153 · 2020: 96
FWCI
127.17
Type
journal article
Language
en
Open access
Licence
www.nejmgroup.org/legal/terms-of-use.htm (vor)
Locations
  • New England Journal of Medicine (publishedVersion)
  • PubMed (publishedVersion)
  • Kölner Universitäts PublikationsServer (Universität zu Köln) (publishedVersion)
  • Pure Amsterdam UMC (publishedVersion)
  • Data Archiving and Networked Services (DANS) (submittedVersion)
  • Research at the University of Copenhagen (University of Copenhagen) (submittedVersion)
Funders
Akcea Therapeutics
Topics
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipoproteins and Cardiovascular Health
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipid metabolism and disorders
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Cholesterol and Lipid Metabolism
Keywords
lipoprotein(a), antisense oligonucleotides, cardiovascular disease, injection site reactions, genetic risk factors
MeSH terms
Adult, Aged, Hypolipidemic Agents, Cardiovascular Diseases, Cholesterol, Dose-Response Relationship, Drug, Double-Blind Method, Female, Humans, Male, Middle Aged, Oligonucleotides, Risk Factors, Least-Squares Analysis, Lipoprotein(a), Hydroxymethylglutaryl-CoA Reductase Inhibitors

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review