Evidence mapPaperPMID 41604274Full record

Trial reportJournal of the American Society of Nephrology : JASN2026

Inclisiran in Patients with CKD: Post Hoc Pooled Analysis of Three Phase 3 Trials.

Ulf Landmesser, Kausik K Ray, Frederick J Raal, Lorena Garcia Conde, Jackie Han, Wolfgang Koenig, Lawrence A Leiter, Gregory G Schwartz, R Scott Wright, on behalf of the ORION Investigators

3 registry-linked trialsAbstract readClinical Trial, Phase IIIMulticenter StudyRandomized Controlled Trial
In one paragraph

Trial report in Journal of the American Society of Nephrology : JASN, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It reports registered trial NCT03400800. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
field-weighted citation impact
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.

NCT03400800 phase3completed

A Placebo-Controlled, Double-Blind, Randomized Trial to Evaluate the Effect of 300 mg of Inclisiran Sodium Given as Subcutaneous Injections in Subjects With Atherosclerotic Cardiovascular Disease (ASCVD) or ACSVD Risk-Equivalents and Elevated Low-Density Lipoprotein Cholesterol (LDL-C)

Ran2017Enrolled1,617Registered outcomes8Posted comparisons8ConditionsASCVD, Elevated Cholesterol, Risk Factor, CardiovascularArmsInclisiran Sodium, Placebo
Open the trial in the graph
NCT03397121 phase3completednot on this map

Placebo-Controlled, Double-Blind, Randomized Trial to Evaluate the Effect of 300 mg of Inclisiran Sodium Given as Subcutaneous Injections in Subjects With Heterozygous Familial Hypercholesterolemia (HeFH) and Elevated Low-Density Lipoprotein Cholesterol (LDL-C).

TypeinterventionalSponsorThe Medicines CompanyRan2017 to 2019Enrolled482ConditionsHeterozygous Familial Hypercholesterolemia, Elevated CholesterolArmsInclisiran, Placebo
NCT03399370 phase3completednot on this map

A Placebo-Controlled, Double-Blind, Randomized Trial to Evaluate the Effect of 300 mg of Inclisiran Sodium Given as Subcutaneous Injections in Subjects With Atherosclerotic Cardiovascular Disease (ASCVD) and Elevated Low-Density Lipoprotein Cholesterol (LDL-C)

TypeinterventionalSponsorThe Medicines CompanyRan2017 to 2019Enrolled1,561ConditionsASCVD, Elevated CholesterolArmsInclisiran Sodium, Placebo
3 · Its place in the literature

Who cites it

3 citing papers in PubMed.

  1. Review
  2. Article
  3. Inclisiran in CKD: A Therapeutic Answer to a Persistent Treatment Gap.Journal of the American Society of Nephrology : JASN · 2026
    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

10 authors.

Ulf LandmesserDepartment of Cardiology, Angiology and Intensive Care Medicine, Deutsches Herzzentrum der Charité, Charité-Universitätsmedizin Berlin, Berlin Institute of Health, DZHK, Partner Site Berlin, Friede Springer Cardiovascular Prevention Center at Charité, Berlin, Germany.ORCID 0000-0002-0214-3203
Kausik K RayDepartment of Primary Care and Public Health, Imperial Centre for Cardiovascular Disease Prevention, Imperial College, London, United Kingdom.ORCID 0000-0003-0508-0954
Frederick J RaalDepartment of Medicine, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.ORCID 0000-0002-9170-7938
Lorena Garcia CondeNovartis Pharma AG, Basel, Switzerland.
Jackie HanNovartis Pharmaceuticals Corporation, East Hanover, New Jersey.
Wolfgang KoenigGerman Heart Centre, School of Medicine and Health, TUM University Hospital, Technical University of Munich, Munich, Germany.ORCID 0000-0002-2064-9603
Lawrence A LeiterLi Ka Shing Knowledge Institute, St. Michael's Hospital, University of Toronto, Toronto, Ontario, Canada.ORCID 0000-0002-1040-6229
Gregory G SchwartzDivision of Cardiology, University of Colorado School of Medicine, Aurora, Colorado.ORCID 0000-0003-2954-0695
R Scott WrightDivision of Preventive Cardiology, Department of Cardiology, Mayo Clinic, Rochester, Minnesota.ORCID 0000-0002-0625-0444
on behalf of the ORION Investigators

Funding

Novartis Pharma AG
6 · The paper itself

Abstract

key pointsInclisiran for LDL cholesterol reduction was analyzed post hoc in patients with CKD. Mean percentage LDL cholesterol reduction from baseline was around 50% regardless of eGFR in phase 3 trials. Inclisiran showed sustained and effective LDL cholesterol-lowering in patients across various levels of eGFR values, without new safety findings.

backgroundLowering LDL cholesterol reduces the risk of atherosclerotic cardiovascular disease in patients with CKD. The efficacy and safety of inclisiran versus placebo in patients without and with CKD were investigated in a post hoc pooled analysis of three phase 3 trials (ORION-9, ORION-10, and ORION-11).

methodsPatients with heterozygous familial hypercholesterolemia, atherosclerotic cardiovascular disease or its risk equivalent, and elevated LDL cholesterol were randomized 1:1 to subcutaneous inclisiran or placebo on days 1 and 90 and every 6 months thereafter for 540 days. Patients were stratified based on baseline eGFR (by CKD Epidemiology Collaboration equation): ≥90, 60 to <90, 45 to <60, and 15 to <45 ml/min per 1.73 m 2 . Coprimary end points were percentage change in LDL cholesterol at day 510 and time-adjusted percentage change after day 90 and through day 540. Safety was also evaluated.

resultsOf 3660 patients, 1610 (44%) had eGFR ≥90, 1608 (44%) 60 to <90, 300 (8%) 45 to <60, and 142 (4%) 15 to <45 ml/min per 1.73 m 2 . The mean (95% confidence interval) placebo-corrected percentage changes in LDL cholesterol from baseline at day 510 in patients with eGFR ≥90, 60 to <90, 45 to <60, and 15 to <45 ml/min per 1.73 m 2 were -49.9% (-53.2 to -46.6), -51.2% (-54.4 to -48.0), -54.7% (-62.5 to -47.0), and -44.7% (-57.6 to -31.8), respectively ( P < 0.001); the corresponding mean (95% confidence interval) time-adjusted placebo-corrected percentage changes in LDL cholesterol from baseline after day 90 through day 540 were -48.4% (-50.8 to -46.1), -51.8% (-54.2 to -49.4), -55.6% (-61.0 to -50.2), and -50.4% (-59.3 to -41.5; each P < 0.001). Significant decreases in total cholesterol, apolipoprotein B, non-HDL cholesterol, and lipoprotein(a) occurred in all eGFR groups. Inclisiran was well tolerated without new safety findings.

conclusionsInclisiran demonstrated sustained and effective LDL cholesterol reduction in patients with or at risk of atherosclerotic cardiovascular disease, regardless of baseline eGFR as low as 15 ml/min per 1.73 m 2 , without new safety findings. CLINICAL TRIAL REGISTRY NAME AND REGISTRATION NUMBER: ClinicalTrials.gov, ORION-9 ( NCT03397121 ), ORION-10 ( NCT03399370 ), and ORION-11 ( NCT03400800 ).

Indexed as

Anticholesteremic AgentsCholesterol, LDLHyperlipoproteinemia Type IIRenal Insufficiency, ChronicAdultAgedAtherosclerosisFemaleGlomerular Filtration RateHumansMaleMiddle AgedRNA, Small InterferingTreatment OutcomeALN-PCSAnticholesteremic AgentsCholesterol, LDLRNA, Small Interferingatherosclerosisatherosclerotic cardiovascular diseaseCKDeGFRinclisiranlipid therapylow-density lipoprotein cholesterolPCSK9 inhibitor

Identifiers

PMID41604274
PMCPMC13337159

What Socratic holds

Textmetadata
LicenceCC BY
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.