Small interfering ribonucleic acid for cholesterol lowering - Inclisiran: Inclisiran for cholesterol lowering

Despite the development of new therapies to lower cardiovascular disease (CVD) risk in recent decades, the trend of reductions in CVD mortality has reversed. New therapies are essential for the prevention of first and recurrent CVD. The importance of lowering low-density lipoprotein cholesterol (LDL-C) in the management and prevention of atherosclerotic CVD (ASCVD) is widely reflected in clinical treatment guidelines; however, most patients with established ASCVD do not achieve guideline-recommended LDL-C targets. Common reasons include adherence challenges, public disinformation, statin tolerability issues, access barriers, and clinical inertia. Inclisiran is a novel small interfering ribonucleic acid (RNA) that lowers circulating LDL-C by ∼50% when added to maximally tolerated statins by mimicking the body's natural pathway of RNA interference to specifically prevent proprotein convertase subtilisin/kexin type 9 synthesis. The unique dosing regimen of inclisiran (initial, at 3 months, and then every 6 months) has the advantage of allowing for healthcare provider administration during recommended routine visits for patients with established ASCVD, which can circumvent adherence issues associated with currently available LDL-C-lowering therapies. Inclisiran has demonstrated favorable tolerability and safety for up to 3 years, and evidence from longer-term use is accumulating in ongoing studies. This review discusses the novel mechanism of action of inclisiran and its potential position in the clinical armamentarium.