Medical Dialogues
  • Dermatology
Login Register
This site is intended for healthcare professionals only
Login Register
  • MD Brand Connect
  • Vaccine Hub
  • MDTV
    • Breaking News
    • Medical News Today
    • Health News Today
    • Latest
    • Journal Club
    • Medico Legal Update
    • Latest Webinars
    • MD Shorts
    • Health Dialogues
  • Fact Check
  • Health Dialogues
Medical Dialogues
  • Medical News & Guidelines
      • Anesthesiology
      • Cardiology and CTVS
      • Critical Care
      • Dentistry
      • Dermatology
      • Diabetes and Endocrinology
      • ENT
      • Gastroenterology
      • Medicine
      • Nephrology
      • Neurology
      • Obstretics-Gynaecology
      • Oncology
      • Ophthalmology
      • Orthopaedics
      • Pediatrics-Neonatology
      • Psychiatry
      • Pulmonology
      • Radiology
      • Surgery
      • Urology
      • Laboratory Medicine
      • Diet
      • Nursing
      • Paramedical
      • Physiotherapy
  • Health news
      • Doctor News
      • Government Policies
      • Hospital & Diagnostics
      • International Health News
      • Medical Organization News
      • Medico Legal News
      • NBE News
      • NMC News
  • Fact Check
      • Bone Health Fact Check
      • Brain Health Fact Check
      • Cancer Related Fact Check
      • Child Care Fact Check
      • Dental and oral health fact check
      • Diabetes and metabolic health fact check
      • Diet and Nutrition Fact Check
      • Eye and ENT Care Fact Check
      • Fitness fact check
      • Gut health fact check
      • Heart health fact check
      • Kidney health fact check
      • Medical education fact check
      • Men's health fact check
      • Respiratory fact check
      • Skin and hair care fact check
      • Vaccine and Immunization fact check
      • Women's health fact check
  • AYUSH
    • Ayurveda
    • Homeopathy
    • Siddha
    • Unani
    • Yoga
  • State News
      • Andaman and Nicobar Islands
      • Andhra Pradesh
      • Arunachal Pradesh
      • Assam
      • Bihar
      • Chandigarh
      • Chattisgarh
      • Dadra and Nagar Haveli
      • Daman and Diu
      • Delhi
      • Goa
      • Gujarat
      • Haryana
      • Himachal Pradesh
      • Jammu & Kashmir
      • Jharkhand
      • Karnataka
      • Kerala
      • Ladakh
      • Lakshadweep
      • Madhya Pradesh
      • Maharashtra
      • Manipur
      • Meghalaya
      • Mizoram
      • Nagaland
      • Odisha
      • Puducherry
      • Punjab
      • Rajasthan
      • Sikkim
      • Tamil Nadu
      • Telangana
      • Tripura
      • Uttar Pradesh
      • Uttrakhand
      • West Bengal
  • Medical Education
      • Ayush Education News
      • Dentistry Education News
      • Medical Admission News
      • Medical Colleges News
      • Medical Courses News
      • Medical Universities News
      • Nursing education News
      • Paramedical Education News
      • Study Abroad
  • Industry
      • Health Investment News
      • Health Startup News
      • Medical Devices News
      • Pharma News
      • Pharmacy Education News
      • Industry Perspective
  • MDTV
      • Health Dialogues MDTV
      • Health News today MDTV
      • Latest Videos MDTV
      • Latest Webinars MDTV
      • MD shorts MDTV
      • Medical News Today MDTV
      • Medico Legal Update MDTV
      • Top Videos MDTV
      • Health Perspectives MDTV
      • Journal Club MDTV
      • Medical Dialogues Show
This site is intended for healthcare professionals only
LoginRegister
Medical Dialogues
LoginRegister
  • Home
  • Medical news & Guidelines
    • Anesthesiology
    • Cardiology and CTVS
    • Critical Care
    • Dentistry
    • Dermatology
    • Diabetes and Endocrinology
    • ENT
    • Gastroenterology
    • Medicine
    • Nephrology
    • Neurology
    • Obstretics-Gynaecology
    • Oncology
    • Ophthalmology
    • Orthopaedics
    • Pediatrics-Neonatology
    • Psychiatry
    • Pulmonology
    • Radiology
    • Surgery
    • Urology
    • Laboratory Medicine
    • Diet
    • Nursing
    • Paramedical
    • Physiotherapy
  • Health news
    • Doctor News
    • Government Policies
    • Hospital & Diagnostics
    • International Health News
    • Medical Organization News
    • Medico Legal News
    • NBE News
    • NMC News
  • Fact Check
    • Bone Health Fact Check
    • Brain Health Fact Check
    • Cancer Related Fact Check
    • Child Care Fact Check
    • Dental and oral health fact check
    • Diabetes and metabolic health fact check
    • Diet and Nutrition Fact Check
    • Eye and ENT Care Fact Check
    • Fitness fact check
    • Gut health fact check
    • Heart health fact check
    • Kidney health fact check
    • Medical education fact check
    • Men's health fact check
    • Respiratory fact check
    • Skin and hair care fact check
    • Vaccine and Immunization fact check
    • Women's health fact check
  • AYUSH
    • Ayurveda
      • Ayurveda Giuidelines
      • Ayurveda News
    • Homeopathy
      • Homeopathy Guidelines
      • Homeopathy News
    • Siddha
      • Siddha Guidelines
      • Siddha News
    • Unani
      • Unani Guidelines
      • Unani News
    • Yoga
      • Yoga Guidelines
      • Yoga News
  • State News
    • Andaman and Nicobar Islands
    • Andhra Pradesh
    • Arunachal Pradesh
    • Assam
    • Bihar
    • Chandigarh
    • Chattisgarh
    • Dadra and Nagar Haveli
    • Daman and Diu
    • Delhi
    • Goa
    • Gujarat
    • Haryana
    • Himachal Pradesh
    • Jammu & Kashmir
    • Jharkhand
    • Karnataka
    • Kerala
    • Ladakh
    • Lakshadweep
    • Madhya Pradesh
    • Maharashtra
    • Manipur
    • Meghalaya
    • Mizoram
    • Nagaland
    • Odisha
    • Puducherry
    • Punjab
    • Rajasthan
    • Sikkim
    • Tamil Nadu
    • Telangana
    • Tripura
    • Uttar Pradesh
    • Uttrakhand
    • West Bengal
  • Medical Education
    • Ayush Education News
    • Dentistry Education News
    • Medical Admission News
    • Medical Colleges News
    • Medical Courses News
    • Medical Universities News
    • Nursing education News
    • Paramedical Education News
    • Study Abroad
  • Industry
    • Health Investment News
    • Health Startup News
    • Medical Devices News
    • Pharma News
      • CDSCO (Central Drugs Standard Control Organisation) News
    • Pharmacy Education News
    • Industry Perspective
  • Home
  • Cardiology-CTVS
  • Cardiology & CTVS News
  • Inclisiran fails to...

Inclisiran fails to find place in AACE 2025 Dyslipidemia Guidelines

Nidhi SrivastavaWritten by Nidhi Srivastava Published On 2025-02-22T08:45:35+05:30  |  Updated On 22 Feb 2025 2:44 PM IST
Inclisiran fails to find place in AACE 2025 Dyslipidemia Guidelines
  • facebook
  • twitter
  • linkedin
  • whatsapp
  • Telegram
  • Email

Ohio: Once pegged as a blockbuster medicine for lowering LDL, long-acting small interfering RNA, Inclisiran failed to find any place in the recently released American Association of Clinical Endocrinology guideline

A recent American Association of Clinical Endocrinology guideline on the pharmacologic management of dyslipidemia in adults 2025 proposed that the current evidence is insufficient to establish a definitive recommendation for or against the use of Inclisiran to reduce the risk of atherosclerotic cardiovascular disease (ASCVD).

The guidelines published in the Endocrine Practice highlighted that only a few clinical trials have been conducted, and the available data on cardiovascular events is too limited to determine whether inclisiran provides significant benefits or poses any risks when added to standard care.

Inclisiran, a small interfering RNA therapy, has demonstrated a significant reduction in low-density lipoprotein cholesterol (LDL-C) levels and has been approved by the USFDA since 2021 and by the Indian CDSCO since 2023. Inclisiran is a long-acting, synthetic small interfering RNA (siRNA) directed against proprotein convertase subtilisin-kexin type 9 (PCSK9), which is a serine protease that regulates plasma low-density lipoprotein cholesterol (LDL-C) levels. By binding to PCSK9 messenger RNA, inclisiran prevents protein translation of PCSK9, leading to decreased concentrations of PCSK9 and plasma concentrations of LDL cholesterol.

However, its impact on cardiovascular outcomes remains uncertain due to lack of well-powered, long-term studies. While all evaluated lipid-lowering medications effectively reduce LDL-C, their impact on mortality and cardiovascular events remains unclear. Consequently, the guidelines issue conditional recommendations for the use of alirocumab, evolocumab, and bempedoic acid in adults with or at increased risk for ASCVD.

Ongoing large-scale clinical trials, including ORION-4 (NCT03705234) and VICTORION-2 PREVENT (NCT05030428), are expected to provide additional insights upon completion in 2026 and 2027, respectively. These trials aim to evaluate inclisiran’s effects on urgent coronary revascularization and all-cause mortality, with VICTORION-2 PREVENT also assessing major limb adverse events—a clinically significant factor in treatment decision-making.

A systematic review of randomized controlled trials (RCTs) evaluating the efficacy of inclisiran in adults with dyslipidemia indicates that the drug does not provide a statistically significant reduction in major cardiovascular events over a follow-up period of 30 to 77 weeks. Across a sample size ranging from 3,655 to 3,739 participants, inclisiran demonstrated no clinically meaningful effect on all-cause mortality (OR 1.01, 95% CI 0.59-1.71), cardiovascular-related mortality (OR 1.11, 95% CI 0.56-2.23), stroke (OR 0.69, 95% CI 0.11-4.21), or myocardial infarction (OR 0.85, 95% CI 0.36-1.98). Additionally, the likelihood of treatment discontinuation due to adverse events was slightly higher in the inclisiran cohort (OR 1.21, 95% CI 0.77-1.88), though this finding was not statistically significant. The certainty of evidence for all reported outcomes was rated as low, highlighting potential bias and imprecision in effect estimates. Furthermore, data on coronary revascularization and peripheral vascular disease (PVD) events were unavailable in the reviewed studies.

The guidelines noted that studies do not demonstrate clinically meaningful benefits of inclisiran in reducing mortality or cardiovascular events when added to usual care. While minor absolute risk reductions were observed—such as three fewer strokes and myocardial infarctions per 1,000 participants—these effects fall within confidence intervals that include potential harms. Similarly, no significant difference was observed in all-cause and cardiovascular-related mortality rates. Adverse events, primarily injection site reactions and bronchitis, led to a small number of treatment discontinuations, though these were considered trivial. Given these findings, inclisiran’s net clinical benefit remains uncertain, with its effects deemed marginal by expert reviewers.

"Due to limited clinical evidence, it remains unclear whether inclisiran’s potential cardiovascular and mortality benefits outweigh possible risks when used alongside usual care. To address these uncertainties, robust, long-term cardiovascular outcomes trials are needed to assess its efficacy in reducing cardiovascular events, its impact on mortality, and its long-term safety profile," the guidelines noted

A discussion published in the Endocrinology and Metabolism Institute noted that inclisiran was not included in the 2017 AACE guidelines as it was unapproved then and, as of 2025, remains without a recommendation due to insufficient evidence for relevant clinical outcomes of interest.

The guidelines also recommend pharmacotherapy to reduce the risk of atherosclerotic cardiovascular disease events. It highlights several effective and safe treatment options for adults with dyslipidemia, particularly those with ASCVD or at increased risk, who require additional lipid-lowering medications.

Reference:

Patel SB, Wyne KL, Afreen S, Belalcazar LM, Bird MD, Coles S, Marrs JC, Peng CC, Pulipati VP, Sultan S, Zilbermint M. American Association of Clinical Endocrinology Clinical Practice Guideline on Pharmacologic Management of Adults With Dyslipidemia. Endocr Pract. 2025 Feb;31(2):236-262.

Correa R. Highlights of the 2025 American Association of Clinical Endocrinology Clinical Practice Guideline on Pharmacologic Management of Adults With Dyslipidemia. Endocr Pract. 2024 Dec 18:S1530-891X(24)00831-0. doi: 10.1016/j.eprac.2024.11.006. Epub ahead of print. PMID: 39918518.

Inclisiran, International Innovator Prescribing Information, Leqvia, Last Revised June,2024: URL: https://www.leqviohcp.com/dosing-and-administration

inclisirandyslipidemiacardiovascular
Nidhi Srivastava
Nidhi Srivastava

    Nidhi Srivastava is a dietician. She holds a post-graduate degree in Nutrition and Dietetics from MRIIRS. With a profound passion for utilizing nutrition and lifestyle modifications to manage diseases, she is dedicated to advancing the field through rigorous research and fact-checking. Her expertise lies in evidence-based practice, ensuring the highest standards of dietary health and wellness.

    Show Full Article
    Next Story

    Editorial

    Real-World Case study: Darbepoetin Alfa for Chemotherapy-Induced Anemia in Metastatic Breast Cancer - Dr Aditya Murali

    Real-World Case study: Darbepoetin Alfa for Chemotherapy-Induced Anemia in Metastatic Breast Cancer...

    Aspirin in Primary Prevention- When to Consider?

    Aspirin in Primary Prevention- When to Consider?

    Featured image representing medico legal

    What's the Role of Expert Opinion in Medical Negligence?

    7- Point Discharge Protocol for AECOPD: Time to Inculcate in Practice

    7- Point Discharge Protocol for AECOPD: Time to Inculcate in Practice

    Aspirin Use in Women Aged 40-50 with Diabetes and Hypertension: Identifying the Ideal Candidates

    Aspirin Use in Women Aged 40-50 with Diabetes and Hypertension: Identifying the Ideal Candidates

    View All

    Journal Club Today

    Real-World Case study: Darbepoetin Alfa for Chemotherapy-Induced Anemia in Metastatic Breast Cancer - Dr Aditya Murali

    Real-World Case study: Darbepoetin Alfa for Chemotherapy-Induced Anemia in Metastatic Breast Cancer...

    View All

    Health News Today

    Health Bulletin 09/ May/ 2025

    Health Bulletin 09/ May/ 2025

    View All
    © 2022 All Rights Reserved.
    Powered By: Hocalwire
    X
    We use cookies for analytics, advertising and to improve our site. You agree to our use of cookies by continuing to use our site. To know more, see our Cookie Policy and Cookie Settings.Ok