The Hurdle of Access to Emerging Therapies and Potential Solutions in the Management of Dyslipidemias

Journal of Clinical Medicine, Journal Year: 2024, Volume and Issue: 13(14), P. 4160 - 4160

Published: July 16, 2024

This review explores the many barriers to accessing lipid-lowering therapies (LLTs) for prevention and management of atherosclerotic cardiovascular disease (ASCVD). Geographical, knowledge, regulatory significantly impede access LLTs, exacerbating disparities in healthcare infrastructure affordability. We highlight importance policy reforms, including pricing regulations reimbursement policies, enhancing affordability streamlining processes. Innovative funding models, such as value-based outcome-based payment arrangements, have been recommended make novel LLTs more accessible. Public health interventions, community-based programs telemedicine, can be utilized reach underserved populations improve medication adherence. Education advocacy initiatives led by patient groups providers play a crucial role raising awareness empowering patients. Despite access, present big opportunity reduce burden ASCVD, emphasizing need collaborative efforts among policymakers, providers, industry stakeholders, address these globally.

Language: Английский

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Emerging Trends and Innovations in the Treatment and Diagnosis of Atherosclerosis and Cardiovascular Disease: A Comprehensive Review towards Healthier Aging

Pharmaceutics, Journal Year: 2024, Volume and Issue: 16(8), P. 1037 - 1037

Published: Aug. 3, 2024

Cardiovascular diseases (CVDs) are classed as of aging, which associated with an increased prevalence atherosclerotic lesion formation caused by such and is considered one the leading causes death globally, representing a severe health crisis affecting heart blood vessels. Atherosclerosis described chronic condition that can lead to myocardial infarction, ischemic cardiomyopathy, stroke, peripheral arterial disease date, most pharmacological therapies mainly aim control risk factors in patients cardiovascular disease. Advances transformative imaging diagnostics agents could shape clinical applications approaches, including nanomedicine, biomaterials, immunotherapy, cell therapy, gene emerging likely significantly impact CVD management coming decade. This review summarizes current anti-atherosclerotic therapies’ major milestones, strengths, limitations. It provides overview recent discoveries technologies immune therapeutics revolutionize practice steering it toward precision medicine. CVD-related trials promising pre-clinical strategies would discussed. Here, we these advances, highlighting key opportunities rapidly field

Language: Английский

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Emerging clinical role of proprotein convertase subtilisin/kexin type 9 inhibition–Part two: Current and emerging concepts in the clinical use of PCSK9 inhibition

European Journal of Clinical Investigation, Journal Year: 2024, Volume and Issue: 54(10)

Published: June 26, 2024

Abstract Background Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors have emerged as a novel class of drugs with cardioprotective effects through their lipid‐lowering effects. Objective This review aims to discuss existing and strategies PCSK9 inhibition, providing an overview established randomized controlled trials ongoing outcome that assess the efficacy long‐term safety inhibitors. It also explores evolving role beyond lipid metabolism outlines pleiotropic actions inhibition in various disorders future directions including target PCSK9. Conclusion shows promise not only but other disease processes, atherosclerotic plaque remodeling, acute coronary syndrome, stroke, inflammation, immune response.

Language: Английский

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A Systematic Review with Network Meta-analysis on Atherosclerosis Vaccine Based on Nonhuman Primate Model

Journal of Preventive Diagnostic and Treatment Strategies in Medicine, Journal Year: 2025, Volume and Issue: 4(1), P. 18 - 25

Published: Jan. 1, 2025

Abstract BACKGROUND: The regulation of plasma low-density lipoprotein cholesterol (LDL-C) levels and receptor (LDLR) function is largely dependent on proprotein convertase subtilisin/kexin type 9 (PCSK9). PCSK9-targeted vaccinations have been designed to produce PCSK9-specific antibodies, which may improve dyslipidemia lower the risk cardiovascular disease. purpose this study was conduct a frequentist network meta-analysis animal trials determine most effective PCSK9 vaccine designs for improving lipid profiles. METHODS: A comprehensive search PubMed, Scopus, Web Science studies published before October 2024 carried out. There were that used in dyslipidemic nonhuman primates. analysis utilized random-effects model with effect size metrics standardized mean difference 95% confidence intervals. Heterogeneity investigated using I² statistics. RESULTS: Four between 2021 satisfied inclusion requirements, covering five different epitope sequences, delivery mechanisms, carriers. Three significant lowering LDL-C: (1) full peptide immunogen containing T-helper B-cell epitopes (VXX-401, P < 0.025); (2) linear PCSK9-derived Qß bacteriophage virus-like particles (rhPCSK9 VLPs, 0.001); (3) mimic (cleavage-resistant mutant) linked shark-derived scaffold (HIT01-K21Q-R218E, 0.037). VXX-401 has higher effectiveness as compared rhPCSK9 VLPs ( = 0.005) HIT01-K21Q-R218E 0.007). low moderate all I ² =0%–26%). CONCLUSION: Because its improved lipid-lowering performance studies, being considered prospective option further atherosclerosis vaccine. findings from present offer valuable insight advancement therapeutic strategies atherosclerosis.

Language: Английский

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Oral PCSK9 Inhibitors: Will They Work?

Current Atherosclerosis Reports, Journal Year: 2025, Volume and Issue: 27(1)

Published: April 30, 2025

Language: Английский

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PCSK9 vaccines: a promising new strategy for the treatment of hypercholesterolemia?

Journal of Lipid Research, Journal Year: 2024, Volume and Issue: 65(3), P. 100524 - 100524

Published: Feb. 17, 2024

VXX-401, a novel anti-PCSK9 vaccine, reduces LDL-C in cynomolgus monkeysJournal of Lipid ResearchVol. 65Issue 2PreviewAtherosclerotic cardiovascular disease (ASCVD) remains the leading cause burden world and is highly correlated with chronic elevations LDL-C. LDL-C-lowering drugs, such as statins or monoclonal antibodies against proprotein convertase subtilisin/kexin type 9 (PCSK9), are known to reduce risk diseases; however, associated limited efficacy poor adherence treatment, whereas PCSK9 inhibitors only prescribed "high-risk" patient population those who have failed other therapies. Full-Text PDF Open Access Management elevated LDL-C, causal factor development atherosclerotic (ASCVD), has been revolutionized by using (PCSK9). When used conjunction statins, can markedly lower levels that not previously attained lipid-lowering medications. Circulating normally cleared from plasma when it taken up hepatocytes express LDL receptor (LDL-R). PCSK9, secretory protein largely produced liver, negatively regulates homeostasis mediating internalization degradation LDL-R. Naturally occurring mutations increase activity higher circulating downregulate lead low serum ASCVD. Currently, two classes approved US Food Drug Administration. These include (mAbs), evolocumab alirocumab, an siRNA-based therapeutic, inclisiran. In hypercholesterolemic individuals these drugs dramatically levels, often much 60% more (1Ray K.K. Stoekenbroek R.M. Kallend D. Leiter L.A. Landmesser U. Wright R.S. et al.Effect siRNA therapeutic targeting on atherogenic lipoproteins: prespecified secondary end points ORION 1.Circulation. 2018; 138: 1304-1316Crossref PubMed Scopus (117) Google Scholar, 2Robinson J.G. Farnier M. Krempf Bergeron J. Luc G. Averna al.Efficacy safety alirocumab reducing lipids events.N. Engl. Med. 2015; 372: 1489-1499Crossref (1710) 3Sabatine M.S. Giugliano R.P. Wiviott S.D. Raal F.J. Blom D.J. Robinson 1500-1509Crossref (1373) Scholar). The widespread adoption inhibitors, relatively slow, due their high cost. Consequently, reserved for high-risk patients prevention fail achieve target conventional statin-based therapies (4Landmesser Chapman M.J. Stock J.K. Amarenco P. Belch J.J.F. Boren al.New prospects inhibition?.Eur. Heart 39: 2600-2601Crossref Another limitation mAbs require regular subcutaneous injections every 2–4 weeks, which complicates utilization adherence. practical issues prompted efforts develop accessible and/or longer lasting alternatives inhibiting oral drug inhibitor (5Siddiqui Z. Frishman W. New inhibitor: "MK-0616".Cardiol. Rev. 2024; https://doi.org/10.1097/CRD.0000000000000655Crossref Scholar), gene editing approach (6Lee R.G. Mazzola A.M. Braun M.C. Platt C. Vafai S.B. Kathiresan S. investigational single-course CRISPR base-editing therapy nonhuman primate mouse models.Circulation. 2023; 147: 242-253Crossref (41) vaccines (7Fowler A. Van Rompay K.K.A. Sampson Leo Watanabe Usachenko J.L. al.A virus-like particle-based bivalent vaccine lowers LDL-cholesterol non-human primates.NPJ Vaccines. 8: 142Crossref (1) 8Vroom M.M. Lu H. Lewis Thibodeaux B.A. Brooks Longo al.VXX-401, monkeys.J. Res. 65100497Abstract Full Text (0) 9Zeitlinger Bauer Reindl-Schwaighofer R. Lambert Berger-Sieczkowski E. phase I study assessing safety, tolerability, immunogenicity, low-density lipoprotein cholesterol-lowering immunotherapeutics PCSK9.Eur. Clin. Pharmacol. 2021; 77: 1473-1484Crossref (26) this issue Journal Research, Vroom colleagues report results promising candidate primates (8Vroom VXX-401 peptide-based elicits targeted antibody responses epitope catalytic domain PCSK9. Although established effective intervention infectious diseases, presents unique challenges inherent difficulties eliciting immune self-antigens. overcomes tolerance mechanisms physically linking peptide strong T helper derived foreign antigen combining potent AdjuPhos/CpG1 adjuvant cocktail. elicited high-titer macaques resulted ∼30–40% reduction relative control group unvaccinated animals. Importantly, immunization did affect HDL-C was any adverse events, inflammation uncontrolled autoimmunity lack effects upon vaccination suggests inducing may be safe approach. one several currently under development. AT04A AT06A developed AFFiRiS AG already undergone clinical trials (9Zeitlinger also link PCSK9-like carrier protein, but sequences modified native human sequence (AT04A) (AT06A) amino acid substitutions. rationale underlying strategy nonself better able overcome self-tolerance could still elicit cross-react trials, were administered Alhydrogel well tolerated. However, decreased while its lowering modest (11%–13% reductions), sustained at level would likely beneficial ASCVD events (10Stone N.J. Lichtenstein A.H. Bairey Merz C.N. Blum C.B. Eckel R.H. al.2013 ACC/AHA guideline treatment blood cholesterol adults: American College Cardiology/American Association Task Force Practice Guidelines.Circulation. 2014; 129: S1-S45Crossref (3263) We takes advantage observation displaying self-antigens surface repetitive, multivalent structure efficiently B cell tolerance. Using bacteriophage particle–based platform, we generated targets epitopes within 153–163 aa (which both AT04A) second (207–223 aa) interacts primates, (administered Alhydrogel) well-tolerated, responses, reduced ∼30% Vaccination, unlike current mAb therapies, typically affordable intervention, potentially allows broader access inhibitors. Vaccines readily distributed globally, allowing avenue address regions globe advanced even now off patent inexpensive. potential stimulate prolonged obviating need frequent administrations, improve compliance, major therapy. Interestingly, longevity three candidates varied. short half-life, just over 2 waned IgG declined contrast, (in humans) had half-life 12 weeks Scholar) 20 mice) It unclear why differences exist stem technology specific adjuvants employed. Nevertheless, will boosting sustain effects. Indeed, booster restoring titers peak Thus, successful implementation ultimately comprehensive understanding precise required possibly new approaches addressing variability amongst individuals. summary, research developmental work needs done vaccines, time they appear great adding our armamentarium disease. authors inventors VLP-based This funded National Institutes Health grant R01HL131696 (B. C.) Intramural Research Program NHLBI. content solely responsibility does necessarily represent official views Health.

Language: Английский

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Transforming hypercholesterolemia management: Spotlight on PCSK9 peptide vaccines

Cell Reports Medicine, Journal Year: 2024, Volume and Issue: 5(9), P. 101726 - 101726

Published: Sept. 1, 2024

Language: Английский

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Management of Hypercholesterolemia in Patients with Coronary Artery Disease: A Glimpse into the Future

Journal of Clinical Medicine, Journal Year: 2024, Volume and Issue: 13(23), P. 7420 - 7420

Published: Dec. 5, 2024

Cardio-cerebral vascular diseases due to atherosclerosis are still the leading cause of death worldwide. Low-density lipoprotein cholesterol (LDL-C) and apolipoprotein B have been identified as primary factors responsible for atherosclerotic process, with a causal effect. Many drugs aimed at reducing LDL-C levels already on market, acting in different ways terms mechanism action, efficacy, safety. Moreover, new lipid-lowering agents technologies fields gene editing immunotherapy currently under investigation. A more recent biomarker associated an increased risk plaque generation, progression, subsequent ASCVD is (a) and, next few years, it will be target pharmacological therapy. The aim this review present landscape therapies approved reduce levels, evaluating their tolerability, indications. we take glimpse into future evaluate experimental novel lower that years or clinical evaluation.

Language: Английский

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Human vaccines and immunotherapeutics: News February 2024

Human Vaccines & Immunotherapeutics, Journal Year: 2024, Volume and Issue: 20(1)

Published: March 13, 2024

Language: Английский

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Pleiotropic Effects of PCSK9 Inhibitors on Cardio-Cerebrovascular Diseases

Biomedicines, Journal Year: 2024, Volume and Issue: 12(12), P. 2729 - 2729

Published: Nov. 28, 2024

Cardiovascular disease (CVD) and ischemic stroke (IS) are the primary causes of mortality worldwide. Hypercholesterolemia has been recognized as an independent risk factor for CVD IS. Numerous clinical trials have unequivocally demonstrated that reducing levels low-density lipoprotein cholesterol (LDL-C) significantly mitigates both cardiac cerebral vascular events, thereby enhancing patient prognosis. Consequently, LDL-C reduction remains a pivotal therapeutic strategy However, despite intensive statin therapy, significant proportion high-risk hypercholesterolemic patients fail to achieve sufficient reductions in levels. In response this challenge, inhibitor targeting proprotein convertase subtilisin-kexin type 9 (PCSK9) developed intervention hyperlipidemia. randomized controlled (RCTs) conclusively combination PCSK9 inhibitors statins enhances prognosis not only with CVD, but also those afflicted symptomatic intracranial artery stenosis (sICAS). reduce by binding molecule preventing its interaction LDLRs. This prevents degradation receptor increases uptake LDL-C, decreasing concentration blood. Besides levels, demonstrate anti-inflammatory anti-atherosclerotic properties while promoting plaque stabilization inhibiting platelet aggregation thrombosis. article aims provide comprehensive review based on relevant literature regarding evolving understanding pleiotropic effects associated inhibitors, particularly focusing their impact cardiovascular system central nervous system.

Language: Английский

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