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PCSK9 Inhibitors and Cardiovascular Diseases: A New Era of Lipid Lowering Therapy

A special issue of Journal of Clinical Medicine (ISSN 2077-0383). This special issue belongs to the section "Cardiovascular Medicine".

Deadline for manuscript submissions: closed (30 April 2022) | Viewed by 11475

Special Issue Editor

Prof. Francesco Giallauria

E-Mail Website
Guest Editor
Department of Translational Medical Sciences, "Federico II" University of Naples, Via S. Pansini 5, 80131 Naples, Italy
Interests: PCSK9 inhibitors; lipid lowering therapy; secondary prevention; very high-risk patients; cardiovascular prevention

Special Issue Information

Dear Colleagues,

Preventing cardiovascular disease (CVD) continues to represent a challenge for clinicians worldwide. CVD is already the leading cause of death and disability. Undoubtedly, clinicians should focus major efforts not only on targeting lifestyle but also ensuring that modifiable cardiovascular risk factors are managed successfully, particularly in individuals at high risk. There is incontrovertible evidence that low-density lipoprotein cholesterol (LDL-C) is a principal driver of atherosclerotic vascular disease, responsible for the clinical manifestations of CVD, and thus, the key target for intervention. The magnitude of clinical benefit in preventing CVD events relates to the extent of LDL-C lowering. Lowering LDL-C is equally critically related to improved plaque stability and decreased atheroma volume. Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors represent the ultimate hope of developing PCSK9-targeted therapeutics to address the unmet clinical needs of high cardiovascular risk patients. These agents efficaciously lower LDL cholesterol and Lp(a); moreover, potential effects on triglyceride-rich lipoproteins, atherogenic remnants, and even HDL particles cannot be excluded at this time. This Special Issue aims at collecting the newest evidence of ongoing research on PCSK9 inhibitors.

Prof. Francesco Giallauria
Guest Editor

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Keywords

  • PCSK9 inhibitors
  • lipid lowering therapy
  • secondary prevention
  • very high-risk patients
  • cardiovascular prevention
  • cardiac rehabilitation
  • acute coronary syndrome
  • lipid profile

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Published Papers (3 papers)

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Research

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8 pages, 511 KiB  
Article
Effect of PCSK9 Inhibitors on Hemostasis in Patients with Isolated Hypercholesterolemia
by Marcin Basiak, Marcin Hachula, Michal Kosowski and Boguslaw Okopien
J. Clin. Med. 2022, 11(9), 2542; https://doi.org/10.3390/jcm11092542 - 1 May 2022
Cited by 12 | Viewed by 2094
Abstract
Background: In addition to reducing plasma lipids, proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors may produce numerous nonlipid-related pleiotropic effects. The purpose of this trial was to determine the efficacy of PCSK9 inhibitors alone in patients with isolated hypercholesterolemia. Methods: The trial enrolled [...] Read more.
Background: In addition to reducing plasma lipids, proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors may produce numerous nonlipid-related pleiotropic effects. The purpose of this trial was to determine the efficacy of PCSK9 inhibitors alone in patients with isolated hypercholesterolemia. Methods: The trial enrolled 21 individuals with isolated hypercholesterolemia and atherosclerosis who received alirocumab for 90 days (150 mg every two weeks). Lipids, glucose homeostasis factors, and hemostatic markers were measured in the plasma at baseline and after treatment. Results: The PCSK9 inhibitor administered to these patients reduced plasma levels/activity of fibrinogen (from 3.6 ± 0.5 to 2.9 ± 0.4 g/L, p < 0.01), factor VII (from 143.8 ± 16.7 to 114.5 ± 14.1%, p < 0.01) and plasminogen activator inhibitor-1 (PAI-1) (from 74.9 ± 13.9 to 52.8 ± 9.1 ng/mL, p < 0.001) without a significant reduction in von Willebrand factor levels, and it tended to prolong the partial thromboplastin and prothrombin times. Conclusion: Our findings indicate that treatment with PCSK9 inhibitors has a multipotential effect on fibrinolysis and coagulation in patients with isolated hypercholesterolemia and that this medication may have some future benefits in patients who are statin-intolerant or contraindicated to statin use. Full article
(This article belongs to the Special Issue PCSK9 Inhibitors and Cardiovascular Diseases: A New Era of Lipid Lowering Therapy)
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Review

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16 pages, 1169 KiB  
Review
Antisense Oligonucleotides and Small Interfering RNA for the Treatment of Dyslipidemias
by Clarice Gareri, Alberto Polimeni, Salvatore Giordano, Laura Tammè, Antonio Curcio and Ciro Indolfi
J. Clin. Med. 2022, 11(13), 3884; https://doi.org/10.3390/jcm11133884 - 4 Jul 2022
Cited by 31 | Viewed by 5525
Abstract
The burden of atherosclerotic disease worldwide necessitates implementing the treatment of its risk factors. Among them, hypercholesterolemia has a central role. In addition to conventional small organic compounds and the recently introduced monoclonal antibodies, new technologies are arising such as the antisense oligonucleotides [...] Read more.
The burden of atherosclerotic disease worldwide necessitates implementing the treatment of its risk factors. Among them, hypercholesterolemia has a central role. In addition to conventional small organic compounds and the recently introduced monoclonal antibodies, new technologies are arising such as the antisense oligonucleotides and small interfering RNAs (siRNAs) that operate upstream, blocking the mRNA translation of the proteins specifically involved in lipid metabolism. In this review, we briefly explain the mechanisms of action of these molecules and discuss the difficulties related to their in vivo use as therapeutical agents. We go over the oligonucleotides tested in clinical trials that could potentially revolutionize the care of patients by acting on proteins involved in the lipoprotein metabolism and regulation, namely: angiopoietin-like protein 3 (ANGPTL3); lipoprotein a (Lp(a)); apolipoprotein B (Apo B); apolipoprotein C III (Apo C-III); and proprotein convertase subtilisin–kexin type 9 (PCSK9). Finally, the differences between ASOs and siRNAs, their future possible clinical applications, and the role of Inclisiran, a siRNA direct against PCSK9 to reduce LDL-C, were reviewed in detail. Full article
(This article belongs to the Special Issue PCSK9 Inhibitors and Cardiovascular Diseases: A New Era of Lipid Lowering Therapy)
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15 pages, 2011 KiB  
Review
Proprotein Convertase Subtilisin/Kexin Type 9 Inhibitors Use for Atherogenic Dyslipidemia in Solid Organ Transplant Patients
by Gianluigi Cuomo, Giuseppe Cioffi, Anna Di Lorenzo, Francesca Paola Iannone, Giuseppe Cudemo, Anna Maria Iannicelli, Mario Pacileo, Antonello D’Andrea, Carlo Vigorito, Gabriella Iannuzzo and Francesco Giallauria
J. Clin. Med. 2022, 11(11), 3247; https://doi.org/10.3390/jcm11113247 - 6 Jun 2022
Cited by 3 | Viewed by 3126
Abstract
Dyslipidemia is a widespread risk factor in solid organ transplant patients, due to many reasons, such as the use of immunosuppressive drugs, with a consequent increase in cardiovascular diseases in this population. PCSK9 is an enzyme mainly known for its role in altering [...] Read more.
Dyslipidemia is a widespread risk factor in solid organ transplant patients, due to many reasons, such as the use of immunosuppressive drugs, with a consequent increase in cardiovascular diseases in this population. PCSK9 is an enzyme mainly known for its role in altering LDL levels, consequently increasing cardiovascular risk. Monoclonal antibody PCSK9 inhibitors demonstrated remarkable efficacy in the general population in reducing LDL cholesterol levels and preventing cardiovascular disease. In transplant patients, these drugs are still poorly used, despite having comparable efficacy to the general population and giving fewer drug interactions with immunosuppressants. Furthermore, there is enough evidence that PCSK9 also plays a role in other pathways, such as inflammation, which is particularly dangerous for graft survival. In this review, the current evidence on the function of PCSK9 and the use of its inhibitors will be discussed, particularly in transplant patients, in which they may provide additional benefits. Full article
(This article belongs to the Special Issue PCSK9 Inhibitors and Cardiovascular Diseases: A New Era of Lipid Lowering Therapy)
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