Abstract
Inclisiran is a small interfering RNA that blocks hepatocyte production of the PCSK9 (proprotein convertase subtilisin/kexin type 9) protein by specifically targeting PCKS9 mRNA in the cytoplasm. This results in reduced degradation of LDL receptors and thus lowers LDL cholesterol by around 50% in addition to other lipid-lowering therapies. beyond 6 years of therapy. This review covers the latest published data and outlines future studies currently in process. To date, half a million doses have been given worldwide with no untoward adverse events thus far. The twice-yearly injections make it potentially very user-friendly. The large phase 3a trials saw no diminution of effect with time up to nearly 7 years. Very large phase 3b randomized controlled trials are underway and may produce significant reductions in major adverse cardiovascular events. Inclisiran has been evaluated in numerous trials, primarily the ORION 9 26 , ORION 10 27 and ORION 11 28 studies, which demonstrated that in patients already on maximally tolerated statin therapy, biannual inclisiran injections reduced LDL cholesterol by up to 52% compared to placebo with a good safety profile. The only observed side effects were mild and transient at the injection site. As mentioned in the accompanying video, this adds to our armamentarium of lipid treatments.
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