Evidence mapPaperPMID 38456415Full record

ReviewJournal of the American Heart Association2024

Harnessing RNA Interference for Cholesterol Lowering: The Bench-to-Bedside Story of Inclisiran.

Michael J Wilkinson, Archna Bajaj, Margaret E Brousseau, Pam R Taub

Open access · goldAbstract readReview
In one paragraph

Review in Journal of the American Heart Association, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
20citing papers in PubMed, 1 pooled it
16.6field-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

20 citing papers in PubMed, 1 synthesis or guideline pooled it, 29 citations in OpenAlex.

  1. Pooled it
  2. Review
  3. RNA-Based Therapies for Inherited Metabolic Disorders.Journal of inherited metabolic disease · 2026
    Review
  4. Article
  5. Review
  6. Review
  7. Article
  8. Review
  9. Lipid-Lowering RNA Therapeutics for Atherosclerotic Cardiovascular Disease Prevention: A State-of-the-Art Review.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2025
    Review
  10. Review
  11. Review
  12. Review
  13. Life Course Approach for Managing Familial Hypercholesterolemia.Journal of the American Heart Association · 2025
    Review
  14. Review
  15. Review
  16. Review
  17. Article
  18. Clinical Considerations for Healthcare Provider-Administered Lipid-Lowering Medications.American journal of cardiovascular drugs : drugs, devices, and other interventions · 2024
    Review
  19. Review
  20. Article
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

4 authors at 2 institutions in 1 country.

Michael J WilkinsonDivision of Cardiovascular Medicine, Department of Medicine Cardiovascular Institute, University of California San Diego San Diego CA USA.ORCID 0000-0002-3800-7369
Archna BajajDepartment of Medicine Perelman School of Medicine at the University of Pennsylvania Philadelphia PA USA.ORCID 0000-0001-7397-6520
Margaret E BrousseauCardiovascular and Metabolism Disease Area, Novartis Institutes for BioMedical Research Cambridge MA USA.
Pam R TaubDivision of Cardiovascular Medicine, Department of Medicine Cardiovascular Institute, University of California San Diego San Diego CA USA.ORCID 0000-0002-0684-0655
Cardiovascular Institute of the South · USUniversity of Pennsylvania · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Lowering low-density lipoprotein cholesterol (LDL-C) is a cornerstone of reducing risk for atherosclerotic cardiovascular disease. Despite the approval of nonstatin therapies for LDL-C lowering over the past 2 decades, these medications are underused, and most patients are still not at guideline-recommended LDL-C goals. Barriers include poor adherence, clinical inertia, concern for side effects, cost, and complex prior authorization processes. With atherosclerotic cardiovascular disease-related mortality increasing globally, there remains a need for additional therapeutic options for lowering LDL-C as part of an atherosclerotic cardiovascular disease prevention strategy. Following the identification of PCSK9 (proprotein convertase subtilisin/kexin type 9) as a promising therapeutic target, inclisiran was developed using the natural process of RNA interference for robust, sustained prevention of hepatic PCSK9 synthesis. Twice-yearly maintenance subcutaneous inclisiran (following initial loading doses at Day 1 and Day 90) reduces circulating LDL-C levels by ≈50% versus placebo when added to maximally tolerated statins. Long-term safety and tolerability of inclisiran have been assessed, with studies underway to evaluate the effects of inclisiran on cardiovascular outcomes and to provide additional safety and effectiveness data. In 2021, <20 years after the discovery of PCSK9, inclisiran became the first RNA interference therapeutic approved in the United States for LDL-C lowering in patients with established atherosclerotic cardiovascular disease or familial hypercholesterolemia and has since been approved for use in patients with primary hyperlipidemia. This article reviews the journey of inclisiran from bench to bedside, including early development, the clinical trial program, key characteristics of inclisiran, and practical points for its use in the clinic.

Indexed as

Anticholesteremic AgentsCardiovascular DiseasesCholesterolCholesterol, LDLHumansPCSK9 InhibitorsProprotein Convertase 9RNA InterferenceRNA, Small InterferingALN-PCSAnticholesteremic AgentsCholesterolCholesterol, LDLPCSK9 InhibitorsPCSK9 protein, humanProprotein Convertase 9RNA, Small Interferingatherosclerotic cardiovascular diseaseinclisiranlow‐density lipoprotein cholesterolproprotein convertase subtilisin/kexin type 9small interfering RNA

Identifiers

PMID38456415
PMCPMC11010004
OpenAlexW4392594886

What Socratic holds

Texttitle and abstract
LicenceCC BY-NC
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 Socratic graph.