ReviewJournal of the American Heart Association2024
Harnessing RNA Interference for Cholesterol Lowering: The Bench-to-Bedside Story of Inclisiran.
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.
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.
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.
Who cites it
20 citing papers in PubMed, 1 synthesis or guideline pooled it, 29 citations in OpenAlex.
- Inclisiran SiRNA therapy for durable LDL-C reduction: a systematic review and meta-analysis highlighting a breakthrough in long-term cardiovascular risk management.BMC cardiovascular disorders · 2026Pooled it
- Emerging biomedical and pharmaceutical strategies for the treatment of atherosclerosis: from conventional lipid-lowering therapy to nanomedicine.Journal of applied biomedicine · 2026Review
- RNA-Based Therapies for Inherited Metabolic Disorders.Journal of inherited metabolic disease · 2026Review
- Engineering Optimized EV-Mimetic Carriers for Efficient Tumor-Targeted Delivery of Functional RNA Nanoparticles.ACS nano medicine · 2026Article
- Review
- A narrative review of PCSK9 inhibitors: from evolocumab to novel discoveries.Frontiers in pharmacology · 2026Review
- RNA-Targeted Therapeutics for Lipid Metabolic Disorders: From Bench to Bedside.Research (Washington, D.C.) · 2026Article
- Review
- Lipid-Lowering RNA Therapeutics for Atherosclerotic Cardiovascular Disease Prevention: A State-of-the-Art Review.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2025Review
- A Comprehensive Review of the Latest Approaches to Managing Hypercholesterolemia: A Comparative Analysis of Conventional and Novel Treatments: Part II.Pharmaceuticals (Basel, Switzerland) · 2025Review
- Review
- The Role of Non-Statin Lipid Lowering Therapies to Reduce ASCVD Events in Primary Prevention.Current atherosclerosis reports · 2025Review
- Life Course Approach for Managing Familial Hypercholesterolemia.Journal of the American Heart Association · 2025Review
- Oral and Non-Oral Cholesterol-Lowering Drugs with PCSK9 and Other Biomolecules as Targets: Present Status and Future Prospects.Biomolecules · 2025Review
- Inclisiran, Reasons for a Novel Agent in a Crowded Therapeutic Field.Current atherosclerosis reports · 2025Review
- Current usage of inclisiran for cardiovascular diseases: overview of current clinical trials.Frontiers in pharmacology · 2025Review
- A Facile and Promising Delivery Platform for siRNA to Solid Tumors.Molecules (Basel, Switzerland) · 2024Article
- Clinical Considerations for Healthcare Provider-Administered Lipid-Lowering Medications.American journal of cardiovascular drugs : drugs, devices, and other interventions · 2024Review
- The Impact of COVID-19 on RNA Therapeutics: A Surge in Lipid Nanoparticles and Alternative Delivery Systems.Pharmaceutics · 2024Review
- Addressing Knowledge Gaps in the Primary Prevention of Atherosclerotic Heart Disease.Journal of the American Heart Association · 2024Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
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.
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What Socratic holds
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.