Literature DB >> 36087240

PCSK9 Inhibitor Wars: How Does Inclisiran Fit in with Current Monoclonal Antibody Inhibitor Therapy? Considerations for Patient Selection.

Natalie Arnold1,2, Wolfgang Koenig3,4,5.   

Abstract

PURPOSE OF REVIEW: Treatment of dyslipidemia represents one of the most crucial strategies to reduce risk of atherosclerotic cardiovascular (CV) disease (ASCVD). In this review, we critically summarize our knowledge on emerging cholesterol-lowering therapy, targeting PCSK9, paying particular attention on treatment allocation of two drug groups, currently available for clinical use, namely, anti-PCSK9 monoclonal antibodies (mAbs) and inclisiran, a first-in-class small interfering RNA against PCSK9. RECENT
FINDINGS: Although both drug classes show a pronounced, but fairly similar reduction in LDL-cholesterol, their long-term safety is still unknown. Compared to mAbs, inclisiran has a more favorable dosing regimen with biannual application that might improve therapeutic adherence significantly. However, a CV outcome trial (CVOT) for inclisiran is still missing. If inclisiran will be safe and effective in ongoing/future CVOTs, it has a huge potential to overcome medication non-compliance, thereby providing a powerful therapeutic option to decrease the burden of ASCVD.
© 2022. The Author(s).

Entities:  

Keywords:  Alirocumab; Dyslipidemia; Evolocumab; Inclisiran; PCSK9 mAb; Small interfering RNA

Year:  2022        PMID: 36087240     DOI: 10.1007/s11886-022-01782-6

Source DB:  PubMed          Journal:  Curr Cardiol Rep        ISSN: 1523-3782            Impact factor:   3.955


  46 in total

1.  Sequence variations in PCSK9, low LDL, and protection against coronary heart disease.

Authors:  Jonathan C Cohen; Eric Boerwinkle; Thomas H Mosley; Helen H Hobbs
Journal:  N Engl J Med       Date:  2006-03-23       Impact factor: 91.245

Review 2.  Atherosclerosis.

Authors:  Peter Libby; Julie E Buring; Lina Badimon; Göran K Hansson; John Deanfield; Márcio Sommer Bittencourt; Lale Tokgözoğlu; Eldrin F Lewis
Journal:  Nat Rev Dis Primers       Date:  2019-08-16       Impact factor: 52.329

Review 3.  Molecular biology of PCSK9: its role in LDL metabolism.

Authors:  Jay D Horton; Jonathan C Cohen; Helen H Hobbs
Journal:  Trends Biochem Sci       Date:  2007-01-09       Impact factor: 13.807

4.  Low LDL cholesterol in individuals of African descent resulting from frequent nonsense mutations in PCSK9.

Authors:  Jonathan Cohen; Alexander Pertsemlidis; Ingrid K Kotowski; Randall Graham; Christine Kim Garcia; Helen H Hobbs
Journal:  Nat Genet       Date:  2005-01-16       Impact factor: 38.330

5.  Decreased plasma cholesterol and hypersensitivity to statins in mice lacking Pcsk9.

Authors:  Shirya Rashid; David E Curtis; Rita Garuti; Norma N Anderson; Yuriy Bashmakov; Y K Ho; Robert E Hammer; Young-Ah Moon; Jay D Horton
Journal:  Proc Natl Acad Sci U S A       Date:  2005-04-01       Impact factor: 11.205

Review 6.  On the function and homeostasis of PCSK9: reciprocal interaction with LDLR and additional lipid effects.

Authors:  Hagai Tavori; Shirya Rashid; Sergio Fazio
Journal:  Atherosclerosis       Date:  2014-12-17       Impact factor: 5.162

7.  Mutations in PCSK9 cause autosomal dominant hypercholesterolemia.

Authors:  Marianne Abifadel; Mathilde Varret; Jean-Pierre Rabès; Delphine Allard; Khadija Ouguerram; Martine Devillers; Corinne Cruaud; Suzanne Benjannet; Louise Wickham; Danièle Erlich; Aurélie Derré; Ludovic Villéger; Michel Farnier; Isabel Beucler; Eric Bruckert; Jean Chambaz; Bernard Chanu; Jean-Michel Lecerf; Gerald Luc; Philippe Moulin; Jean Weissenbach; Annick Prat; Michel Krempf; Claudine Junien; Nabil G Seidah; Catherine Boileau
Journal:  Nat Genet       Date:  2003-06       Impact factor: 38.330

8.  Adenoviral-mediated expression of Pcsk9 in mice results in a low-density lipoprotein receptor knockout phenotype.

Authors:  Kara N Maxwell; Jan L Breslow
Journal:  Proc Natl Acad Sci U S A       Date:  2004-04-26       Impact factor: 11.205

9.  EU-Wide Cross-Sectional Observational Study of Lipid-Modifying Therapy Use in Secondary and Primary Care: the DA VINCI study.

Authors:  Kausik K Ray; Bart Molemans; W Marieke Schoonen; Periklis Giovas; Sarah Bray; Gaia Kiru; Jennifer Murphy; Maciej Banach; Stefano De Servi; Dan Gaita; Ioanna Gouni-Berthold; G Kees Hovingh; Jacek J Jozwiak; J Wouter Jukema; Robert Gabor Kiss; Serge Kownator; Helle K Iversen; Vincent Maher; Luis Masana; Alexander Parkhomenko; André Peeters; Piers Clifford; Katarina Raslova; Peter Siostrzonek; Stefano Romeo; Dimitrios Tousoulis; Charalambos Vlachopoulos; Michal Vrablik; Alberico L Catapano; Neil R Poulter
Journal:  Eur J Prev Cardiol       Date:  2021-09-20       Impact factor: 7.804

10.  Fulminant parvovirus B19 myocarditis after chemotherapy: full recovery after antiviral therapy with tenofovir.

Authors:  Tobias Koenig; Tibor Kempf; Heinz-Peter Schultheiss; Markus Cornberg; Johann Bauersachs; Andreas Schäfer
Journal:  Clin Res Cardiol       Date:  2021-10-20       Impact factor: 5.460

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