Evidence map›Paper›PMID 32197277›Full record

Trial reportThe New England journal of medicine2020

Inclisiran for the Treatment of Heterozygous Familial Hypercholesterolemia.

Frederick J Raal, David Kallend, Kausik K Ray, Traci Turner, Wolfgang Koenig, R Scott Wright, Peter L J Wijngaard, Danielle Curcio, Mark J Jaros, Lawrence A Leiter and 2 more

2 registry-linked trialsOpen access · bronzeAbstract readClinical Trial, Phase IIIRandomized Controlled Trial
PubMed Publisher
In one paragraph

Trial report in The New England journal of medicine, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 385 papers, 12 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
385citing papers in PubMed, 12 pooled it
97.2field-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.

NCT06865885 phase4recruitingstarted 2025, after this paper: background citation

Study of Optimal LDL-C Value Enhancement With Inclisiran in Patients With Multiple Comorbidities in Which There Are Drug-Drug Interactions Limiting LDL-C Lowering

Ran2025Enrolled100Registered outcomes4Posted comparisons0ConditionsCardiometabolic Syndrome, Drug Interactions, LDL-Cholersterol Lowering, Primary PreventionArmsInclisiran sodium 300 mg (equivalent to 284 mg inclisiran) in 1.5 mL
PMID 27754879PMID 32187462PMID 33663735PMID 37227328PMID 36692678PMID 38078592PMID 35290077PMID 10403851PMID 12654605PMID 35175848other papers from this trial
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
3 · Its place in the literature

Who cites it

385 citing papers in PubMed, 12 syntheses or guidelines pooled it, 774 citations in OpenAlex.

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  7. A Meta-analysis of the Regulation of Low-Density Lipoprotein Cholesterol and Proprotein Convertase Subtilisin-Kexin Type 9 with Inclisiran.American journal of cardiovascular drugs : drugs, devices, and other interventions · 2025 · on this map
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  13. Inclisiran in Patients with CKD: Post Hoc Pooled Analysis of Three Phase 3 Trials.Journal of the American Society of Nephrology : JASN · 2026
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325 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

12 authors at 9 institutions in 6 countries.

Frederick J RaalFrom the Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa (F.J.R.); the Medicines Company, Zurich, Switzerland (D.K.); the Imperial Centre for Cardiovascular Disease Prevention, Department of Primary Care and Public Health, Imperial College, London (K.K.R.); Medpace Reference Laboratories, Cincinnati (T.T.); Deutsches Herzzentrum München, Technische Universität München, and German Center for Cardiovascular Research, Munich Heart Alliance, Munich (W.K.), and the Institute of Epidemiology and Medical Biometry, University of Ulm, Ulm (W.K.) - all in Germany; the Division of Preventive Cardiology and the Department of Cardiology, Mayo Clinic, Rochester, MN (R.S.W.); the Medicines Company, Parsippany, NJ (P.L.J.W., D.C.); Summit Analytical, Denver (M.J.J.); Li Ka Shing Knowledge Institute, St. Michael's Hospital, University of Toronto, Toronto (L.A.L.); and the Department of Vascular Medicine, Academic Medical Center, University of Amsterdam, Amsterdam (J.J.P.K.).
David KallendFrom the Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa (F.J.R.); the Medicines Company, Zurich, Switzerland (D.K.); the Imperial Centre for Cardiovascular Disease Prevention, Department of Primary Care and Public Health, Imperial College, London (K.K.R.); Medpace Reference Laboratories, Cincinnati (T.T.); Deutsches Herzzentrum München, Technische Universität München, and German Center for Cardiovascular Research, Munich Heart Alliance, Munich (W.K.), and the Institute of Epidemiology and Medical Biometry, University of Ulm, Ulm (W.K.) - all in Germany; the Division of Preventive Cardiology and the Department of Cardiology, Mayo Clinic, Rochester, MN (R.S.W.); the Medicines Company, Parsippany, NJ (P.L.J.W., D.C.); Summit Analytical, Denver (M.J.J.); Li Ka Shing Knowledge Institute, St. Michael's Hospital, University of Toronto, Toronto (L.A.L.); and the Department of Vascular Medicine, Academic Medical Center, University of Amsterdam, Amsterdam (J.J.P.K.).
Kausik K RayFrom the Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa (F.J.R.); the Medicines Company, Zurich, Switzerland (D.K.); the Imperial Centre for Cardiovascular Disease Prevention, Department of Primary Care and Public Health, Imperial College, London (K.K.R.); Medpace Reference Laboratories, Cincinnati (T.T.); Deutsches Herzzentrum München, Technische Universität München, and German Center for Cardiovascular Research, Munich Heart Alliance, Munich (W.K.), and the Institute of Epidemiology and Medical Biometry, University of Ulm, Ulm (W.K.) - all in Germany; the Division of Preventive Cardiology and the Department of Cardiology, Mayo Clinic, Rochester, MN (R.S.W.); the Medicines Company, Parsippany, NJ (P.L.J.W., D.C.); Summit Analytical, Denver (M.J.J.); Li Ka Shing Knowledge Institute, St. Michael's Hospital, University of Toronto, Toronto (L.A.L.); and the Department of Vascular Medicine, Academic Medical Center, University of Amsterdam, Amsterdam (J.J.P.K.).ORCID 0000-0003-0508-0954
Traci TurnerFrom the Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa (F.J.R.); the Medicines Company, Zurich, Switzerland (D.K.); the Imperial Centre for Cardiovascular Disease Prevention, Department of Primary Care and Public Health, Imperial College, London (K.K.R.); Medpace Reference Laboratories, Cincinnati (T.T.); Deutsches Herzzentrum München, Technische Universität München, and German Center for Cardiovascular Research, Munich Heart Alliance, Munich (W.K.), and the Institute of Epidemiology and Medical Biometry, University of Ulm, Ulm (W.K.) - all in Germany; the Division of Preventive Cardiology and the Department of Cardiology, Mayo Clinic, Rochester, MN (R.S.W.); the Medicines Company, Parsippany, NJ (P.L.J.W., D.C.); Summit Analytical, Denver (M.J.J.); Li Ka Shing Knowledge Institute, St. Michael's Hospital, University of Toronto, Toronto (L.A.L.); and the Department of Vascular Medicine, Academic Medical Center, University of Amsterdam, Amsterdam (J.J.P.K.).
Wolfgang KoenigFrom the Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa (F.J.R.); the Medicines Company, Zurich, Switzerland (D.K.); the Imperial Centre for Cardiovascular Disease Prevention, Department of Primary Care and Public Health, Imperial College, London (K.K.R.); Medpace Reference Laboratories, Cincinnati (T.T.); Deutsches Herzzentrum München, Technische Universität München, and German Center for Cardiovascular Research, Munich Heart Alliance, Munich (W.K.), and the Institute of Epidemiology and Medical Biometry, University of Ulm, Ulm (W.K.) - all in Germany; the Division of Preventive Cardiology and the Department of Cardiology, Mayo Clinic, Rochester, MN (R.S.W.); the Medicines Company, Parsippany, NJ (P.L.J.W., D.C.); Summit Analytical, Denver (M.J.J.); Li Ka Shing Knowledge Institute, St. Michael's Hospital, University of Toronto, Toronto (L.A.L.); and the Department of Vascular Medicine, Academic Medical Center, University of Amsterdam, Amsterdam (J.J.P.K.).
R Scott WrightFrom the Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa (F.J.R.); the Medicines Company, Zurich, Switzerland (D.K.); the Imperial Centre for Cardiovascular Disease Prevention, Department of Primary Care and Public Health, Imperial College, London (K.K.R.); Medpace Reference Laboratories, Cincinnati (T.T.); Deutsches Herzzentrum München, Technische Universität München, and German Center for Cardiovascular Research, Munich Heart Alliance, Munich (W.K.), and the Institute of Epidemiology and Medical Biometry, University of Ulm, Ulm (W.K.) - all in Germany; the Division of Preventive Cardiology and the Department of Cardiology, Mayo Clinic, Rochester, MN (R.S.W.); the Medicines Company, Parsippany, NJ (P.L.J.W., D.C.); Summit Analytical, Denver (M.J.J.); Li Ka Shing Knowledge Institute, St. Michael's Hospital, University of Toronto, Toronto (L.A.L.); and the Department of Vascular Medicine, Academic Medical Center, University of Amsterdam, Amsterdam (J.J.P.K.).
Peter L J WijngaardFrom the Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa (F.J.R.); the Medicines Company, Zurich, Switzerland (D.K.); the Imperial Centre for Cardiovascular Disease Prevention, Department of Primary Care and Public Health, Imperial College, London (K.K.R.); Medpace Reference Laboratories, Cincinnati (T.T.); Deutsches Herzzentrum München, Technische Universität München, and German Center for Cardiovascular Research, Munich Heart Alliance, Munich (W.K.), and the Institute of Epidemiology and Medical Biometry, University of Ulm, Ulm (W.K.) - all in Germany; the Division of Preventive Cardiology and the Department of Cardiology, Mayo Clinic, Rochester, MN (R.S.W.); the Medicines Company, Parsippany, NJ (P.L.J.W., D.C.); Summit Analytical, Denver (M.J.J.); Li Ka Shing Knowledge Institute, St. Michael's Hospital, University of Toronto, Toronto (L.A.L.); and the Department of Vascular Medicine, Academic Medical Center, University of Amsterdam, Amsterdam (J.J.P.K.).
Danielle CurcioFrom the Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa (F.J.R.); the Medicines Company, Zurich, Switzerland (D.K.); the Imperial Centre for Cardiovascular Disease Prevention, Department of Primary Care and Public Health, Imperial College, London (K.K.R.); Medpace Reference Laboratories, Cincinnati (T.T.); Deutsches Herzzentrum München, Technische Universität München, and German Center for Cardiovascular Research, Munich Heart Alliance, Munich (W.K.), and the Institute of Epidemiology and Medical Biometry, University of Ulm, Ulm (W.K.) - all in Germany; the Division of Preventive Cardiology and the Department of Cardiology, Mayo Clinic, Rochester, MN (R.S.W.); the Medicines Company, Parsippany, NJ (P.L.J.W., D.C.); Summit Analytical, Denver (M.J.J.); Li Ka Shing Knowledge Institute, St. Michael's Hospital, University of Toronto, Toronto (L.A.L.); and the Department of Vascular Medicine, Academic Medical Center, University of Amsterdam, Amsterdam (J.J.P.K.).
Mark J JarosFrom the Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa (F.J.R.); the Medicines Company, Zurich, Switzerland (D.K.); the Imperial Centre for Cardiovascular Disease Prevention, Department of Primary Care and Public Health, Imperial College, London (K.K.R.); Medpace Reference Laboratories, Cincinnati (T.T.); Deutsches Herzzentrum München, Technische Universität München, and German Center for Cardiovascular Research, Munich Heart Alliance, Munich (W.K.), and the Institute of Epidemiology and Medical Biometry, University of Ulm, Ulm (W.K.) - all in Germany; the Division of Preventive Cardiology and the Department of Cardiology, Mayo Clinic, Rochester, MN (R.S.W.); the Medicines Company, Parsippany, NJ (P.L.J.W., D.C.); Summit Analytical, Denver (M.J.J.); Li Ka Shing Knowledge Institute, St. Michael's Hospital, University of Toronto, Toronto (L.A.L.); and the Department of Vascular Medicine, Academic Medical Center, University of Amsterdam, Amsterdam (J.J.P.K.).
Lawrence A LeiterFrom the Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa (F.J.R.); the Medicines Company, Zurich, Switzerland (D.K.); the Imperial Centre for Cardiovascular Disease Prevention, Department of Primary Care and Public Health, Imperial College, London (K.K.R.); Medpace Reference Laboratories, Cincinnati (T.T.); Deutsches Herzzentrum München, Technische Universität München, and German Center for Cardiovascular Research, Munich Heart Alliance, Munich (W.K.), and the Institute of Epidemiology and Medical Biometry, University of Ulm, Ulm (W.K.) - all in Germany; the Division of Preventive Cardiology and the Department of Cardiology, Mayo Clinic, Rochester, MN (R.S.W.); the Medicines Company, Parsippany, NJ (P.L.J.W., D.C.); Summit Analytical, Denver (M.J.J.); Li Ka Shing Knowledge Institute, St. Michael's Hospital, University of Toronto, Toronto (L.A.L.); and the Department of Vascular Medicine, Academic Medical Center, University of Amsterdam, Amsterdam (J.J.P.K.).
John J P KasteleinFrom the Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa (F.J.R.); the Medicines Company, Zurich, Switzerland (D.K.); the Imperial Centre for Cardiovascular Disease Prevention, Department of Primary Care and Public Health, Imperial College, London (K.K.R.); Medpace Reference Laboratories, Cincinnati (T.T.); Deutsches Herzzentrum München, Technische Universität München, and German Center for Cardiovascular Research, Munich Heart Alliance, Munich (W.K.), and the Institute of Epidemiology and Medical Biometry, University of Ulm, Ulm (W.K.) - all in Germany; the Division of Preventive Cardiology and the Department of Cardiology, Mayo Clinic, Rochester, MN (R.S.W.); the Medicines Company, Parsippany, NJ (P.L.J.W., D.C.); Summit Analytical, Denver (M.J.J.); Li Ka Shing Knowledge Institute, St. Michael's Hospital, University of Toronto, Toronto (L.A.L.); and the Department of Vascular Medicine, Academic Medical Center, University of Amsterdam, Amsterdam (J.J.P.K.).
ORION-9 Investigators
Deutsches Herzzentrum München · DEDoctors Company (United States) · USAmsterdam UMC Location University of Amsterdam · NLMayo Clinic in Arizona · USMedpace (United States) · USSt. Michael's Hospital · CASummit (United Kingdom) · GBUniversität Ulm · DEUniversity of the Witwatersrand · ZA

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundFamilial hypercholesterolemia is characterized by an elevated level of low-density lipoprotein (LDL) cholesterol and an increased risk of premature atherosclerotic cardiovascular disease. Monoclonal antibodies directed against proprotein convertase subtilisin-kexin type 9 (PCSK9) have been shown to reduce LDL cholesterol levels by more than 50% but require administration every 2 to 4 weeks. In a phase 2 trial, a twice-yearly injection of inclisiran, a small interfering RNA, was shown to inhibit hepatic synthesis of PCSK9 in adults with heterozygous familial hypercholesterolemia.

methodsIn this phase 3, double-blind trial, we randomly assigned, in a 1:1 ratio, 482 adults who had heterozygous familial hypercholesterolemia to receive subcutaneous injections of inclisiran sodium (at a dose of 300 mg) or matching placebo on days 1, 90, 270, and 450. The two primary end points were the percent change from baseline in the LDL cholesterol level on day 510 and the time-adjusted percent change from baseline in the LDL cholesterol level between day 90 and day 540.

resultsThe median age of the patients was 56 years, and 47% were men; the mean baseline level of LDL cholesterol was 153 mg per deciliter. At day 510, the percent change in the LDL cholesterol level was a reduction of 39.7% (95% confidence interval [CI], -43.7 to -35.7) in the inclisiran group and an increase of 8.2% (95% CI, 4.3 to 12.2) in the placebo group, for a between-group difference of -47.9 percentage points (95% CI, -53.5 to -42.3; P<0.001). The time-averaged percent change in the LDL cholesterol level between day 90 and day 540 was a reduction of 38.1% (95% CI, -41.1 to -35.1) in the inclisiran group and an increase of 6.2% (95% CI, 3.3 to 9.2) in the placebo group, for a between-group difference of -44.3 percentage points (95% CI, -48.5 to -40.1; P<0.001). There were robust reductions in LDL cholesterol levels in all genotypes of familial hypercholesterolemia. Adverse events and serious adverse events were similar in the two groups.

conclusionsAmong adults with heterozygous familial hypercholesterolemia, those who received inclisiran had significantly lower levels of LDL cholesterol than those who received placebo, with an infrequent dosing regimen and an acceptable safety profile. (Funded by the Medicines Company; ORION-9 ClinicalTrials.gov number, NCT03397121.).

Indexed as

Hyperlipoproteinemia Type IIPCSK9 InhibitorsRNA, Small InterferingAdultAnticholesteremic AgentsCholesterol, LDLDouble-Blind MethodFemaleHumansInjections, SubcutaneousMaleMiddle AgedProprotein Convertase 9Treatment OutcomeALN-PCSAnticholesteremic AgentsCholesterol, LDLPCSK9 InhibitorsPCSK9 protein, humanProprotein Convertase 9RNA, Small Interfering

Identifiers

PMID32197277
OpenAlexW3011005820

What OpenQuestion holds

Textmetadata
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 OpenQuestion graph.