Purpose Of Review: Remarkable reductions in cardiovascular morbidity and mortality have been achieved in recent decades through the widespread use of 'small-molecule' hypolipidaemic drugs such as statins and ezetimibe. An alternative approach is to perturb the production of proteins through ribonucleic acid (RNA) silencing, leading to long-lasting knock-down of specific biological molecules. This review describes the scientific basis of RNA silencing, and critically evaluates the evidence relating to inclisiran, a small interfering RNA against proprotein convertase subtilisin kexin 9 (PCSK9).
Recent Findings: Pooled analysis of three recent ORION trials has demonstrated that twice-yearly administration of inclisiran reduces LDL-C by 50% in a range of patient groups, with only mild adverse effects. Inclisiran provides safe, effective and long-lasting reductions in PCSK9 and LDL-C. The results of the phase-3 ORION-4 outcomes study are eagerly awaited. Further promising RNA silencing technologies have the potential to improve the management of dyslipidaemia.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8410691 | PMC |
| http://dx.doi.org/10.1007/s11883-021-00968-7 | DOI Listing |
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