Evidence map›Paper›PMID 26538546›Full record

ReviewJournal of lipid research2016

Antisense inhibition of apolipoprotein (a) to lower plasma lipoprotein (a) levels in humans.

Mark J Graham, Nick Viney, Rosanne M Crooke, Sotirios Tsimikas

Erratum issuedOpen access · hybridAbstract readReview
PubMed Full text at PMC Publisher
In one paragraph

Review in Journal of lipid research, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 53 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
53citing papers in PubMed, 1 pooled it
21.3field-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

53 citing papers in PubMed, 1 synthesis or guideline pooled it, 130 citations in OpenAlex.

  1. Pooled it
  2. On-treatment platelet reactivity through the thromboxane AJournal of thrombosis and thrombolysis · 2023
    Trial
  3. Trial
  4. Trial
  5. Article
  6. Article
  7. Article
  8. Review
  9. Article
  10. Review
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  12. Lipoprotein(a) as a Risk Factor for Cardiovascular Diseases: Pathophysiology and Treatment Perspectives.International journal of environmental research and public health · 2023
    Review
  13. Article
  14. Review
  15. Association of vitamins, minerals, and lead with lipoprotein(a) in a cross-sectional cohort of US adults.International journal for vitamin and nutrition research. Internationale Zeitschrift fur Vitamin- und Ernahrungsforschung. Journal international de vitaminologie et de nutrition · 2023
    Article
  16. Review
  17. Review
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

4 authors at 1 institution in 1 country.

Mark J GrahamIsis Pharmaceuticals University of California San Diego, La Jolla, CA.
Nick VineyIsis Pharmaceuticals University of California San Diego, La Jolla, CA.
Rosanne M CrookeIsis Pharmaceuticals University of California San Diego, La Jolla, CA.
Sotirios TsimikasIsis Pharmaceuticals University of California San Diego, La Jolla, CA Division of Cardiovascular Medicine, University of California San Diego, La Jolla, CA stsimikas@ucsd.edu.
University of California, San Diego · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Epidemiological, genetic association, and Mendelian randomization studies have provided strong evidence that lipoprotein (a) [Lp(a)] is an independent causal risk factor for CVD, including myocardial infarction, stroke, peripheral arterial disease, and calcific aortic valve stenosis. Lp(a) levels >50 mg/dl are highly prevalent (20% of the general population) and are overrepresented in patients with CVD and aortic stenosis. These data support the notion that Lp(a) should be a target of therapy for CVD event reduction and to reduce progression of aortic stenosis. However, effective therapies to specifically reduce plasma Lp(a) levels are lacking. Recent animal and human studies have shown that Lp(a) can be specifically targeted with second generation antisense oligonucleotides (ASOs) that inhibit apo(a) mRNA translation. In apo(a) transgenic mice, an apo(a) ASO reduced plasma apo(a)/Lp(a) levels and their associated oxidized phospholipid (OxPL) levels by 86 and 93%, respectively. In cynomolgus monkeys, a second generation apo(a) ASO, ISIS-APO(a)Rx, significantly reduced hepatic apo(a) mRNA expression and plasma Lp(a) levels by >80%. Finally, in a phase I study in normal volunteers, ISIS-APO(a)Rx ASO reduced Lp(a) levels and their associated OxPL levels up to 89 and 93%, respectively, with minimal effects on other lipoproteins. ISIS-APO(a)Rx represents the first specific and potent drug in clinical development to lower Lp(a) levels and may be beneficial in reducing CVD events and progression of calcific aortic valve stenosis.

Indexed as

AnimalsApolipoproteins AClinical Trials as TopicHumansLipoprotein(a)Oligonucleotides, AntisenseApolipoproteins ALipoprotein(a)Oligonucleotides, Antisenseaortic stenosisatherosclerosismyocardial infarction

Identifiers

PMID26538546
PMCPMC4767000
OpenAlexW2120090218

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

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.