Leqvio (inclisiran) / Alnylam, Novartis - LARVOL DELTA

CHORMONE: The relationship of cholesterol-lowering drugs with steroid HORMONEs, bile acids, muscle morphology, vitamin D, the immune system and related diseases such as depression and osteoporosis (clinicaltrialsregister.eu) - P4 | N=250 | Recruiting | Sponsor: Medical University Of Vienna | Not yet recruiting ➔ Recruiting

Enrollment open • CNS Disorders • Depression • Dyslipidemia • Mood Disorders • Osteoporosis • Psychiatry • Rheumatology

Long-Acting RNA Interference Therapies for Cardiovascular Risk Reduction: Current Evidence and Emerging Targets. (PubMed, Curr Cardiol Rep) - No abstract available

Journal • Review • Cardiovascular • Dyslipidemia • Hypertriglyceridemia

RNA-Based Therapies for Hypercholesterolemia and Coronary Artery Disease. (PubMed, Cureus) - "Pelacarsen and other emerging antisense therapies show promise for reducing lipoprotein(a), an independent cardiovascular risk factor, while siRNAs targeting ANGPTL3 offer prolonged lipid-lowering effects beyond those achieved with monoclonal antibodies...Hepatic safety concerns have halted the development of some agents, such as vupanorsen, and long-term cardiovascular outcome data for several therapies, including inclisiran, are still in development. Cost and accessibility also limit broad adoption, emphasizing the need for cost-effective strategies and long-term surveillance. Nevertheless, current evidence supports the integration of RNA-based therapies into modern lipid-lowering algorithms, particularly for high-risk patients, while ongoing research continues to refine delivery systems, enhance safety, and expand therapeutic indications."

Journal • Review • Cardiovascular • Coronary Artery Disease • Dyslipidemia • Metabolic Disorders • ANGPTL3 • APOB

Post-acute coronary syndrome cardiovascular rehabilitation: insights into endpoints, biomarkers and clinical practice. (PubMed, Heart) - "Pharmacological innovations, such as PCSK9 inhibitors, inclisiran and agents targeting lipoprotein(a) and inflammation, contribute to residual risk reduction when integrated into CR...Addressing these gaps requires harmonised referral systems, multidisciplinary coordination and patient-centred strategies. Ongoing research should focus on integrating emerging therapies and technologies to enhance personalisation, promote equity and expand CR applications across broader patient populations."

Biomarker • Journal • Review • Acute Coronary Syndrome • Cardiovascular • Inflammation

LACK OF RESPONSE TO INCLISIRAN IN HIGH-RISK PATIENTS WITH ADVERSE EFFECTS TO TRADITIONAL LIPID-LOWERING THERAPIES (ACC 2026) - "After three doses, her lipid profile showed no improvement: TC 378 mg/dl, LDL-C 326 mg/dl, HDL-C 37 mg/dl, triglycerides 75 mg/dl...Decision-Making: Due to therapeutic failure, further options considered were monoclonal antibodies against PCSK9 (evolocumab, alirocumab) and/or bempedoic acid in combination with ezetimibe... This case series describes two high-risk patients with coronary atherosclerosis and adverse effects to conventional lipid-lowering therapies who failed to respond to inclisiran. These findings underscore the urgent need for further clinical and translational research to elucidate the biological basis of non-response, identify predictors of therapeutic failure, and optimize patient selection for inclisiran therapy."

Adverse events • Clinical • Acute Coronary Syndrome • Atherosclerosis • Cardiovascular • Coronary Artery Disease • Dyslipidemia • Hepatology • Inflammation • Metabolic Disorders • Musculoskeletal Pain

A CASE OF A DOUBLE-NONRESPONDER TO PCSK9 INHIBIOR THERAPY (ACC 2026) - "Background: The introduction of PCSK9 inhibitors (PCSK9i), including monoclonal antibodies such as evolocumab and small interfering RNA therapies such as inclisiran, has expanded lipid-lowering options for patients intolerant to statins...She had a history of statin-associated muscle symptoms and intolerance to ezetimibe... With the broader adoption of PCSK9i and inclisiran for primary and secondary prevention, rare cases of true non-response will increasingly be recognized. This case underscores the importance of considering alternative pathophysiologic mechanisms beyond known genetic variants. Future research is needed to elucidate predictors of non-response and optimize therapeutic strategies for these patients."

Clinical • Cardiovascular • Dyslipidemia • Familial Hypercholesterolemia • Genetic Disorders • Metabolic Disorders • APOB

EFFECTIVENESS OF INCLISIRAN COMPARED TO ALIROCUMAB/EVOLOCUMAB IN PATIENTS WITH FAMILIAL OR SEVERE HYPERCHOLESTEROLEMIA (ACC 2026) - "Inclisiran produced LDL-C reductions comparable to PCSK9 mAbs across patients with FH or severe hypercholesterolemia, supporting its role as a potent LDL-C lowering therapy in these patients."

Clinical • Diabetes • Dyslipidemia • Familial Hypercholesterolemia • Genetic Disorders • Hypertension • Metabolic Disorders • APOB

UTILIZATION, EXPENDITURE, AND PRICE TRENDS FOR EZETIMIBE AND NOVEL LIPID-LOWERING MEDICATIONS IN U.S. MEDICAID DRUG UTILIZATION DATA, 2002-2024 (ISPOR 2026) - "The analysis included ezetimibe (Zetia® and generic), and novel lipid-lowering medications: evolocumab (Repatha®), alirocumab (Praluent®), inclisiran (Leqvio®), bempedoic acid (Nexletol®), and evinacumab (Evkeeza®). Despite continued dominance of ezetimibe in prescription volume, Medicaid spending has shifted substantially toward high-cost NLLMs. These findings highlight a growing divergence between utilization and expenditure in Medicaid drug spending and underscore the importance of value-based pricing, outcomes-linked contracting, and formulary strategies as adoption of novel lipid-lowering agents expands."

Medicaid • Reimbursement • US reimbursement • ANGPTL3

CKJX839A12309: Evaluation of efficacy and safety of early in hospital initiation of inclisiran treatment in patients with acute coronary syndromes (clinicaltrialsregister.eu) - P2/3 | N=135 | Not yet recruiting | Sponsor: Novartis Pharma AG | N=24 ➔ 135

Enrollment change • Acute Coronary Syndrome • Cardiovascular • Myocardial Infarction

EFFICACY OF INCLISIRAN FOR MORTALITY AND CARDIOVASCULAR EVENT PREVENTION ON PATIENTS WITH ELEVATED LDL CHOLESTEROL: AN UPDATED META-ANALYSIS (ACC 2026) - "In this meta-analysis, inclisiran did not reduce mortality in patients with elevated LDL cholesterol and high or very high ASCVD risk, despite significant reduction on LDL cholesterol levels."

Retrospective data • Atherosclerosis • Cardiovascular • Myocardial Infarction

MANAGING FAMILIAL HYPERCHOLESTEROLEMIA AFTER MYOCARDIAL INFARCTION IN A PATIENT WITH A HISTORY OF RHABDOMYOLYSIS FROM A RARE METABOLIC MYOPATHY: A RARE CASE REPORT AND CLINICAL IMPLICATION (ACC 2026) - "At the time of presentation, his LDL cholesterol was elevated at 164 mg/dL while being treated with ezetimibe 10 mg daily. Selecting lipid-lowering agents for secondary prevention after ACS in patients with a history of severe rhabdomyolysis is complex. In this case, inclisiran proved to be a safe and highly effective therapeutic option, successfully reducing the patient's LDL-C level to 28 mg/dL within a three-month follow-up period without any adverse muscular events."

Case report • Clinical • Acute Coronary Syndrome • Cardiovascular • Dyslipidemia • Familial Hypercholesterolemia • Genetic Disorders • Heterozygous Familial Hypercholesterolemia • Metabolic Disorders • Myocardial Infarction • Myositis • Pulmonary Disease

CARDIOVASCULAR OUTCOMES OF INCLISIRAN USE IN PATIENTS WITH CLINICAL ATHEROSCLEROTIC CARDIOVASCULAR DISEASE (ASCVD) ON MAXIMALLY TOLERATED STATINS: A PROPENSITY-MATCHED ANALYSIS (ACC 2026) - "In a large real-world cohort, inclisiran use alongside maximal statin therapy was associated with reduced MACE, AMI, and hospitalizations. These findings highlight inclisiran's potential to improve cardiovascular outcomes in high-risk ASCVD patients."

Clinical • Atherosclerosis • Cardiovascular • Congestive Heart Failure • Heart Failure • Myocardial Infarction

RAPIDLY ESCALATED LIPID-LOWERING THERAPY EFFECTIVENESS IN PLAQUE STABILIZATION IN PATIENTS WITH ELEVATED LIPOPROTEIN(A) (ACC 2026) - "Aim of this study was to assess the effectiveness of rapidly escalated lipid-lowering therapy to statin/ezetimibe/inclisiran when necessary for plaque lipid reduction using near-infrared spectroscopy (NIRS). In this study rapidly escalated triple lipid lowering therapy effectively reduced plaque lipids at 15 month-follow-up in patients with high Lp(a)."

Clinical • Atherosclerosis • Cardiovascular • Coronary Artery Disease • Dyslipidemia

INCLISIRAN VS PCSK9 MONOCLONAL ANTIBODIES IN CORONARY ARTERY DISEASE: COMPARATIVE EFFECTIVENESS STUDY (ACC 2026) - "In this large real-world cohort of patients with CAD, inclisiran was associated with reduced ischemic events compared with PCSK9 mAbs over 12 months. These findings support the potential of siRNA therapy not only to achieve durable LDL-C lowering but also to improve clinical outcomes, highlighting the need for longer-term comparative effectiveness studies."

HEOR • Cardiovascular • Coronary Artery Disease • Dyslipidemia • Ischemic stroke • Myocardial Infarction

A CASE OF REMARKABLE REDUCTION IN LDL FROM AKKERMANSIA PROBIOTIC (ACC 2026) - "Case: Our patient is a 69-year-old woman with dyslipidemia, coronary calcifications, and intolerance to statins and ezetimibe due to severe myalgias...She later developed a mycobacterium avium infection in 2/2024 prompting 18 months of ethambutol, rifampin, and azithromycin... This is the first case report supporting a lipid lowering effect of Akkermansia, and here it was more than twice as effective as inclisiran. Gut dysbiosis from prolonged antibiotics may have uniquely set her up to be a hyper-responder. Further research on Akkermansia for lipid lowering, and targeted probiotic use in dysbiosis is warranted."

Clinical • Atherosclerosis • Cardiovascular • Dyslipidemia • Infectious Disease • Metabolic Disorders • Musculoskeletal Pain

Act When It Matters Most: When to Consider LEQVIO® (inclisiran) (ACC 2026) - "Sponsored by Novartis Pharmaceuticals"

4012. Act When It Matters Most: When to Consider LEQVIO® (inclisiran) (ACC 2026) - "Don't miss an engaging Industry-Expert Theater that will delve into the latest clinical data, help you identify the appropriate patient profiles, and provide actionable strategies for integrating LEQVIO effectively into your daily practice. Industry-Expert Theater presentations are not part of ACC.26, as planned by its Program Committee, and do not qualify for continuing medical education (CME), continuing nursing education (CNE) or continuing education (CE) credit."

PCSK9 INHIBITOR INCLISIRAN ATTENUATES CARDIOTOXICITY INDUCED BY SEQUENTIAL ANTHRACYCLINE AND TRASTUZUMAB EXPOSURE VIA NLRP3 AND MYD88 PATHWAY INHIBITION (ACC 2026) - " Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) were treated with subclinical concentrations of doxorubicin (1 µM) and trastuzumab (200 nM) in sequential exposure, either alone or combined with inclisiran (100 nM) for 24h. This is the first demonstration that PCSK9i inclisiran exerts strong anti-inflammatory and cardioprotective effects against anthracycline/HER2 inhibitor-induced cardiotoxicity via NLRP3 and MyD88 signaling, independent of lipid-lowering activity. Findings support its role in primary prevention of cancer therapy-related cardiac dysfunction (CTRCD)."

Cardiovascular • CSF2 • IFNG • IL10 • IL12A • IL1B • IL2 • IL4 • IL6 • MFN2 • MYD88 • NLRP3 • TNFA

CLINICAL OUTCOMES AND IMPLEMENTATION OF VALUE STREAM OPTIMIZATION FOR INCLISIRAN ADMINISTRATION IN STATIN-INTOLERANT PATIENTS (ACC 2026) - "Inclisiran demonstrated superior clinical effectiveness with 2-3 fold greater guideline target attainment and excellent safety in statin-intolerant patients. Systematic process improvement significantly enhanced delivery efficiency, with Medicare coverage predicting successful implementation, supporting both clinical efficacy and operational feasibility in real-world practice."

Clinical • Clinical data • Cardiovascular

EFFECTIVENESS OF LDL-C LOWERING WITH ALIROCUMAB AND INCLISIRAN IN A CLINICAL PRACTICE SETTING (ACC 2026) - "Mean age 69; 48% male; 45.3% diabetes; 62.2% statin; 40.6% ezetimibe; baseline LDL-C median 132 mg/dl. Alirocumab achieved consistent, stable LDL-C reductions over 15 months, while inclisiran showed fluctuations consistent with ORION-10/11 and overall lower efficacy"

Clinical • Diabetes • Metabolic Disorders

ROBUST LP(A) REDUCTION WITH COMBINED TOCILIZUMAB AND INCLISIRAN IN A HIGH-RISK INFLAMMATORY PATIENT (ACC 2026) - "Case: A 69-year-old man with hyperlipidemia and coronary artery disease (LAD and LCx stents) had persistently elevated Lp(a) >90 mg/dL over 10 years, which rose further with atorvastatin 20 mg daily...Decision-Making: The patient required long-term prednisone, but symptom recurrence below 10 mg daily prompted tocilizumab, enabling steroid discontinuation... Lp(a) declined substantially with combined tocilizumab and inclisiran. PCSK9 inhibitors typically reduce Lp(a) by ~25%; however, in this patient, an additional 29% reduction was achieved with tocilizumab through interleukin-6 inhibition, which directly suppresses hepatic Lp(a) synthesis. Ongoing trials will clarify whether targeted Lp(a) lowering improves cardiovascular outcomes, but this may represent a viable option for patients with inflammatory disorders to reduce cardiovascular risk."

Clinical • Atherosclerosis • Cardiovascular • Coronary Artery Disease • Dyslipidemia • Giant Cell Arteritis • Immunology • Inflammation • IL6

EARLY AND SUSTAINED LOW-DENSITY LIPOPROTEIN CHOLESTEROL GOAL ATTAINMENT WITH "INCLISIRAN FIRST" IN VICTORION-INITIATE (ACC 2026) - P3 | "Rapid LDL-C goal attainment (<70 mg/dL and <55 mg/dL) from Day 90 was achieved by most pts receiving IF, with consistency across subgroups; most pts subsequently sustained goals to Day 330. Pts rarely achieved LDL-C goals without PCSK9 targeted therapy."

Atherosclerosis • Dyslipidemia

REAL-WORLD UTILIZATION AND PERSISTENCE OF LIPID-LOWERING THERAPIES AFTER PERCUTANEOUS CORONARY INTERVENTION (PCI) (ACC 2026) - "Initiation, persistence, and retention of statins, ezetimibe, PCSK9 inhibitors, inclisiran, and bempedoic acid were assessed. Post-PCI LLT was characterized by delayed initiation, limited persistence, and low non-statin use. The finding that >25% PCI patients had no documented therapy underscores the need for strategies to improve LLT intensification in secondary prevention."

Clinical • Real-world • Real-world evidence • Cardiovascular

Study of the Protective Effect and Mechanism of Inclisiran on Renal Tissue in a Type 2 Diabetes Mouse Model via the Transforming Growth Factor-β Pathway (PubMed, Sichuan Da Xue Xue Bao Yi Xue Ban) - "There were 11 downregulated differentially expressed proteins (P45481: Crebbp, P70387: Hfe, Q61502: E2f5, Q62312: Tgfbr2, Q62432: Smad2, Q8BSK8: Rps6kb1, Q8BUN5: Smad3, Q8CG19: Ltbp1, Q9CUN6: Smurf1, Q9JKX3: Tfr2, Q9Z1M4: Rps6kb2) related to this pathway between groups B and D. Inclisiran may improve the lipid profile of type 2 diabetic mice and reduce the activity of the TGF-β pathway. Its mechanism of action may be related to effects such as extracellular matrix proliferation."

Journal • Preclinical • Diabetes • Dyslipidemia • Metabolic Disorders • Nephrology • Renal Disease • Type 2 Diabetes Mellitus • CREBBP • E2F5 • LTBP1 • RPS6KB1 • RPS6KB2 • SMAD2 • SMAD3 • SMURF1 • TGFB1 • TGFBR2

Intensive lipid-lowering therapy-related regression of a vulnerable plaque confirmed by serial optical coherence tomography: a case report. (PubMed, Front Cardiovasc Med) - "Vulnerable plaques represent a principal pathological driver of acute coronary events. Sustained and effective LLT promotes plaque stabilization and regression, while serial OCT, owing to its high resolution and reproducibility, enables dynamic assessment of plaque morphology and supports individualized management in patients with ACS."

Journal • Acute Coronary Syndrome • Cardiovascular • Myocardial Infarction • Pain • Thrombosis