The DOI matches its Crossref record; 19 of the 19 references it cites were found in a registry or an index.
Two Phase 3 Trials of Inclisiran in Patients with Elevated LDL Cholesterol
Open accessAbstract
BACKGROUND: Inclisiran inhibits hepatic synthesis of proprotein convertase subtilisin-kexin type 9. Previous studies suggest that inclisiran might provide sustained reductions in low-density lipoprotein (LDL) cholesterol levels with infrequent dosing. METHODS: We enrolled patients with atherosclerotic cardiovascular disease (ORION-10 trial) and patients with atherosclerotic cardiovascular disease or an atherosclerotic cardiovascular disease risk equivalent (ORION-11 trial) who had elevated LDL cholesterol levels despite receiving statin therapy at the maximum tolerated dose. Patients were randomly assigned in a 1:1 ratio to receive either inclisiran (284 mg) or placebo, administered by subcutaneous injection on day 1, day 90, and every 6 months thereafter over a period of 540 days. The coprimary end points in each trial were the placebo-corrected percentage change in LDL cholesterol level from baseline to day 510 and the time-adjusted percentage change in LDL cholesterol level from baseline after day 90 and up to day 540. RESULTS: A total of 1561 and 1617 patients underwent randomization in the ORION-10 and ORION-11 trials, respectively. Mean (±SD) LDL cholesterol levels at baseline were 104.7±38.3 mg per deciliter (2.71±0.99 mmol per liter) and 105.5±39.1 mg per deciliter (2.73±1.01 mmol per liter), respectively. At day 510, inclisiran reduced LDL cholesterol levels by 52.3% (95% confidence interval [CI], 48.8 to 55.7) in the ORION-10 trial and by 49.9% (95% CI, 46.6 to 53.1) in the ORION-11 trial, with corresponding time-adjusted reductions of 53.8% (95% CI, 51.3 to 56.2) and 49.2% (95% CI, 46.8 to 51.6) (P<0.001 for all comparisons vs. placebo). Adverse events were generally similar in the inclisiran and placebo groups in each trial, although injection-site adverse events were more frequent with inclisiran than with placebo (2.6% vs. 0.9% in the ORION-10 trial and 4.7% vs. 0.5% in the ORION-11 trial); such reactions were generally mild, and none were severe or persistent. CONCLUSIONS: Reductions in LDL cholesterol levels of approximately 50% were obtained with inclisiran, administered subcutaneously every 6 months. More injection-site adverse events occurred with inclisiran than with placebo. (Funded by the Medicines Company; ORION-10 and ORION-11 ClinicalTrials.gov numbers, NCT03399370 and NCT03400800.).
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.
Integrity signals
Registry
Cites
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.
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?
The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Randomized controlled trials, including the VICTORION-Mono and VICTORION-Difference trials, as well as ORION -10, -11, and other Phase III trials, have consistently demonstrated that inclisiran reduces LDL-C compared with placebo in primary and secondary prevention settings.5, 6, 7”
From Small Interfering RNA for LDL-Cholesterol Reduction (2026) · cites this paper as [7]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“The trials showed that patients achieved LDL-C decreases of 52.3% and 49.9% at Day 510 [44].”
From Inclisiran SiRNA therapy for durable LDL-C reduction: a systematic review and meta-analysis highlighting a breakthrough in long-term cardiovascular risk management (2026) · cites this paper as [44]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“The ORION-10 and ORION-11 trials achieved LDL-C reductions greater than 50% among their participants [44].”
From Inclisiran SiRNA therapy for durable LDL-C reduction: a systematic review and meta-analysis highlighting a breakthrough in long-term cardiovascular risk management (2026) · cites this paper as [44]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“The initial injections of inclisiran at Day 1 and 90 followed by biannual maintenance resulted in a long-term average LDL-C reduction of − 44% to − 48% across ORION-1 and ORION-10 and ORION-11 [25, 44].”
From Inclisiran SiRNA therapy for durable LDL-C reduction: a systematic review and meta-analysis highlighting a breakthrough in long-term cardiovascular risk management (2026) · cites this paper as [44]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Clinical observations demonstrate that numerous patients stop taking their daily statin medications or PCSK9 antibody injections irregularly which reduces their ability to prevent cardiovascular diseases [44, 80].”
From Inclisiran SiRNA therapy for durable LDL-C reduction: a systematic review and meta-analysis highlighting a breakthrough in long-term cardiovascular risk management (2026) · cites this paper as [44]
Experimental — accuracy not yet measured
The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Accordingly, PCSK9 siRNA and monoclonal antibodies blocking the PCSK9/LDLR interaction potently lower LDL cholesterol and reduce the risk of adverse cardiovascular events (Sabatine et al., 2017; Schwartz et al., 2018; Ray et al., 2020).”
From PCSK9 deficiency alters brain lipid composition without affecting brain development and function (2023) · cites this paper as Ray et al., 2020
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Accordingly, PCSK9 inhibitory antibodies and siRNA potently reduce LDL cholesterol to unprecedented low levels and are approved for treatment of hypercholesterolemia.”
From PCSK9 deficiency alters brain lipid composition without affecting brain development and function (2023) · cites this paper as Ray et al., 2020
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“targeted PCSK9 inhibition restores hepatic LDLR levels, decreases plasma LDL-C levels and improves cardiovascular outcomes.7,9–11”
From Sirtuin-1 directly binds and deacetylates hepatic PCSK9 thereby promoting the inhibition of LDL receptor degradation (2025) · cites this paper as [11]
Experimental — accuracy not yet measuredThe cited source says what the claim attributes to it.
In the citing paper
“The phase 3 ORION-10 and ORION-11 trials evaluated inclisiran compared with placebo across a total of 1561 and 1617 patients with atherosclerosis or an atherosclerotic CVD risk-equivalent, respectively [137]. Compared with placebo, inclisiran reduced LDL-C levels by − 52% and − 50%, respectively.”
From Established and Emerging Lipid-Lowering Drugs for Primary and Secondary Cardiovascular Prevention (2023) · cites this paper as [137]
The cited source says what the claim attributes to it.
In the citing paper
“In addition to monoclonal antibodies that sequester PCSK9 in the circulation and are now prescribed to patients, the small-interfering RNA inclisiran that targets PCSK9 hepatic production has recently been approved, following reports of substantial LDL lowering [50% reduction (95% confidence interval 47–53)] with this drug (11).”
From PCSK9 and the nervous system: a no-brainer? (2023) · cites this paper as [11]
The cited source says what the claim attributes to it.
In the citing paper
“In addition to the monoclonal antibodies, an siRNA, inclisiran, which also targets PSCK9, has demonstrated the ability to reduce LDL cholesterol by 49-52% in trials evaluating individuals with established cardiovascular disease or ASCVD risk equivalent (129).”
From 10. Cardiovascular Disease and Risk Management: Standards of Care in Diabetes—2025 (2025) · cites this paper as [129]
The cited source says what the claim attributes to it.
In the citing paper
“In addition to the monoclonal antibodies, an siRNA, inclisiran, which also targets PSCK9 and is referred to as a PCSK9 siRNA in this section, has demonstrated the ability to reduce LDL cholesterol by 49–52% in trials evaluating individuals with established CVD or ASCVD risk equivalent (123).”
From 10. Cardiovascular Disease and Risk Management: Standards of Care in Diabetes—2026 (2026) · cites this paper as [123]
The cited source says what the claim attributes to it.
In the citing paper
“Inclisiran was noted to decrease LDL by ∼50% in the ORION trials [20]”
From Oral PCSK9 inhibitors for elevated LDL-C: A systematic review and meta-analysis of randomized trials (2026) · cites this paper as [20]
The cited source says what the claim attributes to it.
In the citing paper
“The analysis of 11 RCTs for quantitative synthesis included more than 13,000 participants showed inclisiran produces significant LDL-C reduction versus placebo treatment [24, 25, 38–44, 46, 49].”
The cited source says what the claim attributes to it.
In the citing paper
“Large-scale research including well-powered trials such as ORION 10 and ORION 11 demonstrates that Inclisiran shows strong potential as a potent lipid-lowering agent [44].”
In the citing paper
“Patients on statins with high LDL-C levels and ASCVD or at least one ASCVD risk equivalent were included in the two phase 3 trials ORION-10 and ORION-11 (Inclisiran for Participants With Atherosclerotic Cardiovascular Disease and Elevated Low-density Lipoprotein Cholesterol), and obtained a further 50% reduction of LDL-C with inclisiran.278”
From 2023 ESC guidelines for the management of cardiovascular disease in patients with diabetes. (2023) · cites this paper as [278]
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
Multiple Imputation for Nonresponse in Surveys
Rubin, D. B. (1987) · Wiley Series in Probability and Statistics · doi:10.1002/9780470316696 · Cited by 20,701
Mach, F., Baigent, C., Catapano, A. L., Koskinas, K. C., Casula, M., Badimon, L., Chapman, M. J., De Backer, G. G., Delgado, V., Ference, B. A., et al. (2020) · European Heart Journal · doi:10.1093/eurheartj/ehz455 · Cited by 8,961
Self-citationEvolocumab and Clinical Outcomes in Patients with Cardiovascular Disease
Sabatine, M. S., Giugliano, R. P., Keech, A. C., Honarpour, N., Wiviott, S. D., Murphy, S. A., Kuder, J. F., Wang, H., Liu, T., Wasserman, S. M., et al. (2017) · New England Journal of Medicine · doi:10.1056/nejmoa1615664 · Cited by 6,138
Alirocumab and Cardiovascular Outcomes after Acute Coronary Syndrome
Schwartz, G. G., Steg, P. G., Szarek, M., Bhatt, D. L., Bittner, V. A., Diaz, R., Edelberg, J. M., Goodman, S. G., Hanotin, C., Harrington, R. A., et al. (2018) · New England Journal of Medicine · doi:10.1056/nejmoa1801174 · Cited by 3,634
Patisiran, an RNAi Therapeutic, for Hereditary Transthyretin Amyloidosis
Adams, D., Gonzalez-Duarte, A., O’Riordan, W. D., Yang, C.-C., Ueda, M., Kristen, A. V., Tournev, I., Schmidt, H. H., Coelho, T., Berk, J. L., et al. (2018) · New England Journal of Medicine · doi:10.1056/nejmoa1716153 · Cited by 3,047
Grundy, S. M., Stone, N. J., Bailey, A. L., Beam, C., Birtcher, K. K., Blumenthal, R. S., Braun, L. T., de Ferranti, S., Faiella-Tommasino, J., Forman, D. E., et al. (2019) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2018.11.003 · Cited by 2,691
2016 ESC/EAS Guidelines for the Management of Dyslipidaemias
Catapano, A. L., Graham, I., De Backer, G., Wiklund, O., Chapman, M. J., Drexel, H., Hoes, A. W., Jennings, C. S., Landmesser, U., Pedersen, T. R., et al. (2016) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2016.08.018 · Cited by 1,582
Inclisiran in Patients at High Cardiovascular Risk with Elevated LDL Cholesterol
Ray, K. K., Landmesser, U., Leiter, L. A., Kallend, D., Dufour, R., Karakas, M., Hall, T., Troquay, R. P. T., Turner, T., Visseren, F. L. J., et al. (2017) · New England Journal of Medicine · doi:10.1056/nejmoa1615758 · Cited by 992
Self-citationRodríguez, F., Maron, D. J., Knowles, J. W., Virani, S. S., Lin, S., & Heidenreich, P. A. (2019) · JAMA Cardiology · doi:10.1001/jamacardio.2018.4936 · Cited by 347
The Implications of Therapeutic Complexity on Adherence to Cardiovascular Medications
Choudhry, N. K., Fischer, M. A., Avorn, J., Liberman, J. N., Schneeweiß, S., Pakes, J., Brennan, T. A., & Shrank, W. H. (2011) · Archives of Internal Medicine · doi:10.1001/archinternmed.2010.495 · Cited by 314
Phase 1 Trial of an RNA Interference Therapy for Acute Intermittent Porphyria
Sardh, E., Harper, P., Balwani, M., Stein, P. E., Rees, D. C., Bissell, D. M., Desnick, R. J., Parker, C., Phillips, J. D., Bonkovsky, H. L., et al. (2019) · New England Journal of Medicine · doi:10.1056/nejmoa1807838 · Cited by 259
Physician Follow-up and Provider Continuity Are Associated With Long-term Medication Adherence
Brookhart, M. A. (2007) · Archives of Internal Medicine · doi:10.1001/archinte.167.8.847 · Cited by 198
Oligonucleotide Therapeutics — A New Class of Cholesterol-Lowering Drugs
Khvorova, A. (2017) · New England Journal of Medicine · doi:10.1056/nejmp1614154 · Cited by 188
Ray, K. K., Stoekenbroek, R. M., Kallend, D., Nishikido, T., Leiter, L. A., Landmesser, U., Wright, R. S., Wijngaard, P. L. J., & Kastelein, J. J. P. (2019) · JAMA Cardiology · doi:10.1001/jamacardio.2019.3502 · Cited by 172
Self-citationKhunti, K., Danese, M. D., Kutikova, L., Catterick, D., Sorio-Vilela, F., Gleeson, M. L., Seshasai, S. R. K., Brownrigg, J. R. W., & Ray, K. K. (2018) · JAMA Network Open · doi:10.1001/jamanetworkopen.2018.5554 · Cited by 108
Self-citationInclisiran for the Treatment of Cardiovascular Disease: the Orion Clinical Development Program
Stoekenbroek, R. M., Kallend, D. G., Wijngaard, P. L. J., & Kastelein, J. J. P. (2018) · Future Cardiology · doi:10.2217/fca-2018-0067 · Cited by 106
Self-citationRay, K. K., Corral, P., Morales, E., & Nicholls, S. J. (2019) · The Lancet · doi:10.1016/s0140-6736(19)31950-6 · Cited by 94
Self-citationDanese, M. D., Gleeson, M. L., Kutikova, L., Griffiths, R. I., Azough, A., Khunti, K., Seshasai, S. R. K., & Ray, K. K. (2016) · BMJ Open · doi:10.1136/bmjopen-2016-011805 · Cited by 43
Self-citationTargeting Therapeutic Oligonucleotides
Levin, A. A. (2017) · New England Journal of Medicine · doi:10.1056/nejmcibr1613559 · Cited by 35
Flagged first, then by citations
Cited by
Sorted by citations
2021 ESC Guidelines on cardiovascular disease prevention in clinical practice
Visseren, F. L. J., Mach, F., Smulders, Y. M., Carballo, D., Koskinas, K. C., Bäck, M., Benetos, A., Biffi, A., Boavida, J.-M., Capodanno, D., et al. (2021) · European Heart Journal · doi:10.1093/eurheartj/ehab484 · Cited by 6,485
Self-citation2024 ESC Guidelines for the management of chronic coronary syndromes
Vrints, C. J., Andreotti, F., Koskinas, K. C., Rosselló, X., Adamo, M., Ainslie, J., BANNING, A. P., Budaj, A., Buechel, R. R., Chiariello, G. A., et al. (2024) · European Heart Journal · doi:10.1093/eurheartj/ehae177 · Cited by 3,521
2023 ESC guidelines for the management of cardiovascular disease in patients with diabetes.
Marx, N., Federici, M., Schütt, K., Müller-Wieland, D., Ajjan, R. A., Antunes, M. J., Christodorescu, R. M., Crawford, C., Di Angelantonio, E., Eliasson, B., et al. (2023) · European Heart Journal · doi:10.1093/eurheartj/ehad192 · Cited by 1,642
Virani, S. S., Newby, L. K., Arnold, S. V., Bittner, V., Brewer, L. C., Demeter, S. H., Dixon, D. L., Fearon, W. F., Hess, B., Johnson, H. M., et al. (2023) · Circulation · doi:10.1161/cir.0000000000001168 · Cited by 1,598
Drug delivery systems for RNA therapeutics
Paunovska, K., Loughrey, D., & Dahlman, J. E. (2022) · Nature Reviews Genetics · doi:10.1038/s41576-021-00439-4 · Cited by 1,349
Metadata
- Authors
- Ray, K. K., Wright, R. S., Kallend, D., Koenig, W., Leiter, L. A., Raal, F. J., Bisch, J. A., Richardson, T., Jaros, M., Wijngaard, P. L. J., & Kastelein, J. J. P.
- Affiliations
- Mayo Clinic (US)
- From the Imperial Centre for Cardiovascular Disease Prevention, Department of Primary Care and Public Health, Imperial College London, London (K.K.R.); the Department of Cardiology, Mayo Clinic, Rochester, MN (R.S.W.); the Medicines Company, Zurich, Switzerland (D.K.); Deutsches Herzzentrum München, Technische Universität München, and Deutsches Zentrum für Herz-Kreislauf-Forschung (German Center for Cardiovascular Research), partner site Munich Heart Alliance, Munich, and the Institute of...
- St. Michael's Hospital (CA)
- ORCID
- Venue
- New England Journal of Medicine
- Publisher
- Massachusetts Medical Society
- Published
- 2020-04-16
- Volume
- 382
- Issue
- 16
- Pages
- 1507-1519
- ISSN
- 0028-4793 (ISSN-L)
- 1533-4406
- OpenAlex
- W3012265841
- Semantic Scholar
- 0c86cfdc39f60ff6dc8854a281c1b95f32bdc692
- Cited by
- 1,665
- References
- 19
- Citations by year
- 2026: 296 · 2025: 290 · 2024: 289 · 2023: 273 · 2022: 231 · 2021: 193 · 2020: 87
- FWCI
- 183.81
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- New England Journal of Medicine (publishedVersion)
- PubMed (publishedVersion)
- Pure Amsterdam UMC (publishedVersion, other-oa)
- ENLIGHTEN (Jurnal Bimbingan dan Konseling Islam) (acceptedVersion, cc-by-sa)
- IRIS Research product catalog (Sapienza University of Rome) (submittedVersion, other-oa)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- mediaTUM – the media and publications repository of the Technical University Munich (Technical University Munich) (submittedVersion)
- Spiral (Imperial College London) (submittedVersion)
- Funders
- The Medicines Company
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipoproteins and Cardiovascular Health
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Cholesterol and Lipid Metabolism
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipid metabolism and disorders
- Keywords
- inclisiran, PCSK9 inhibition, LDL cholesterol lowering, atherosclerotic cardiovascular disease, statin therapy, injection-site adverse events, hypercholesterolemia, lipid-lowering therapy, adverse events, drug safety and efficacy
- MeSH terms
- Proprotein Convertase 9, PCSK9 Inhibitors, Aged, Aged, 80 and over, Anticholesteremic Agents, Cardiovascular Diseases, Coronary Artery Disease, Double-Blind Method, Drug Administration Schedule, Female, Humans, Hypercholesterolemia, Injections, Subcutaneous, Cholesterol, LDL, Liver Function Tests, Male, Middle Aged, Risk Factors, Hydroxymethylglutaryl-CoA Reductase Inhibitors, RNA, Small Interfering
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
