Clinical potential of inclisiran for patients with a high risk of atherosclerotic cardiovascular disease
Abstract Elevated low-density lipoprotein cholesterol (LDL-C) level is associated with an increased risk of atherosclerotic cardiovascular disease. Although high-intensity lipid-lowering therapies with statins and ezetimibe are highly effective for reducing LDL-C levels, over half of high-risk patie...
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| Format: | Article |
| Language: | English |
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BMC
2023-01-01
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| Series: | Cardiovascular Diabetology |
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| Online Access: | https://doi.org/10.1186/s12933-023-01752-4 |
| _version_ | 1811171892389740544 |
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| author | Toshiyuki Nishikido |
| author_facet | Toshiyuki Nishikido |
| author_sort | Toshiyuki Nishikido |
| collection | DOAJ |
| description | Abstract Elevated low-density lipoprotein cholesterol (LDL-C) level is associated with an increased risk of atherosclerotic cardiovascular disease. Although high-intensity lipid-lowering therapies with statins and ezetimibe are highly effective for reducing LDL-C levels, over half of high-risk patients do not achieve guideline-recommended LDL-C goals. Thus, there is a significant gap between treatment guidelines and their implementation in daily clinical practice. The major causes are individual variability in the response to lipid-lowering therapies and variation in treatment adherence. Proprotein convertase subtilisin/kexin type 9 (PCSK9) monoclonal antibodies combined with statins provide marked and consistent reduction in LDL-C levels; however, poor adherence due to the need for subcutaneous injections every 2 or 4 weeks and high cost are major obstacles to their use in real-world clinical settings. Inclisiran, a recently approved novel small interfering ribonucleic acid (siRNA) molecule that inhibits PCSK9 synthesis, provides robust and long-term reduction in LDL-C levels with a low inter-individual variability in the LDL-C-lowering response. Moreover, its administration by biannual injection is expected to greatly improve treatment adherence. Clinical trials of this drug lasting for up to 4 years showed acceptable safety profiles, and ongoing studies accumulate evidence of its longer-term safety. This narrative review summarizes the available evidence on the efficacy and safety of inclisiran and analyzes its potential to overcome the gap between guideline recommendations and real-world clinical practice in current LDL-C-lowering therapies, with a focus on reduced LDL-C level variability and improved treatment adherence. |
| first_indexed | 2024-04-10T17:21:45Z |
| format | Article |
| id | doaj.art-8f873331588b430ea2843ef6d3f68b75 |
| institution | Directory Open Access Journal |
| issn | 1475-2840 |
| language | English |
| last_indexed | 2024-04-10T17:21:45Z |
| publishDate | 2023-01-01 |
| publisher | BMC |
| record_format | Article |
| series | Cardiovascular Diabetology |
| spelling | doaj.art-8f873331588b430ea2843ef6d3f68b752023-02-05T12:03:59ZengBMCCardiovascular Diabetology1475-28402023-01-0122111210.1186/s12933-023-01752-4Clinical potential of inclisiran for patients with a high risk of atherosclerotic cardiovascular diseaseToshiyuki Nishikido0Department of Cardiovascular Medicine, National Hospital Organization Kobe Medical CenterAbstract Elevated low-density lipoprotein cholesterol (LDL-C) level is associated with an increased risk of atherosclerotic cardiovascular disease. Although high-intensity lipid-lowering therapies with statins and ezetimibe are highly effective for reducing LDL-C levels, over half of high-risk patients do not achieve guideline-recommended LDL-C goals. Thus, there is a significant gap between treatment guidelines and their implementation in daily clinical practice. The major causes are individual variability in the response to lipid-lowering therapies and variation in treatment adherence. Proprotein convertase subtilisin/kexin type 9 (PCSK9) monoclonal antibodies combined with statins provide marked and consistent reduction in LDL-C levels; however, poor adherence due to the need for subcutaneous injections every 2 or 4 weeks and high cost are major obstacles to their use in real-world clinical settings. Inclisiran, a recently approved novel small interfering ribonucleic acid (siRNA) molecule that inhibits PCSK9 synthesis, provides robust and long-term reduction in LDL-C levels with a low inter-individual variability in the LDL-C-lowering response. Moreover, its administration by biannual injection is expected to greatly improve treatment adherence. Clinical trials of this drug lasting for up to 4 years showed acceptable safety profiles, and ongoing studies accumulate evidence of its longer-term safety. This narrative review summarizes the available evidence on the efficacy and safety of inclisiran and analyzes its potential to overcome the gap between guideline recommendations and real-world clinical practice in current LDL-C-lowering therapies, with a focus on reduced LDL-C level variability and improved treatment adherence.https://doi.org/10.1186/s12933-023-01752-4InclisiranLipid-lowering therapiesLow-density lipoprotein cholesterolProprotein convertase subtilisin/kexin type 9Small interfering ribonucleic acidIndividual variability |
| spellingShingle | Toshiyuki Nishikido Clinical potential of inclisiran for patients with a high risk of atherosclerotic cardiovascular disease Cardiovascular Diabetology Inclisiran Lipid-lowering therapies Low-density lipoprotein cholesterol Proprotein convertase subtilisin/kexin type 9 Small interfering ribonucleic acid Individual variability |
| title | Clinical potential of inclisiran for patients with a high risk of atherosclerotic cardiovascular disease |
| title_full | Clinical potential of inclisiran for patients with a high risk of atherosclerotic cardiovascular disease |
| title_fullStr | Clinical potential of inclisiran for patients with a high risk of atherosclerotic cardiovascular disease |
| title_full_unstemmed | Clinical potential of inclisiran for patients with a high risk of atherosclerotic cardiovascular disease |
| title_short | Clinical potential of inclisiran for patients with a high risk of atherosclerotic cardiovascular disease |
| title_sort | clinical potential of inclisiran for patients with a high risk of atherosclerotic cardiovascular disease |
| topic | Inclisiran Lipid-lowering therapies Low-density lipoprotein cholesterol Proprotein convertase subtilisin/kexin type 9 Small interfering ribonucleic acid Individual variability |
| url | https://doi.org/10.1186/s12933-023-01752-4 |
| work_keys_str_mv | AT toshiyukinishikido clinicalpotentialofinclisiranforpatientswithahighriskofatheroscleroticcardiovasculardisease |