P361 SMALL INTERFERING RNA: REAL–LIFE DATA WITH A NEW FRONTIER IN HYPOLIPIDEMIC THERAPY

Abstract

Abstract Inclisiran (Leqvio® 284 mg) is a new small interfering RNA that acts on the mRNA coding for the gene PCSK9. Inclisiran is indicated in adults with primary hypercholesterolemia (heterozygous familial and non–familial) or mixed dyslipidemia as an adjunct to diet alone or in combination with a statin or other lipid–lowering therapies in patients unable to reach LDL–cholesterol goals with the maximum tolerated dose of a statin, or alone or in combination with other lipid–lowering therapies in patients who are statin–intolerant/contraindicated. The drug is administered subcutaneously and should be performed by a healthcare professional. After the initial dose, a second dose is given at 3 months followed by every 6 months. Real–life data with inclisiran is very limited. Herein, we present real–life data on 6 patients with a mean age of 71 years who started therapy with inclisiran in September 2022 (Fig. 1). Three patients were receiving combined lipid–lowering therapy with a statin and exetimibe, 2 were on ezetimibe alone because they were statin–intolerant, 1 patient was not receiving any therapy because intolerant. All patients had high to very high cardiovascular risk according to current ESC guidelines, and the lipid target was not met on optimized oral lipid–lowering therapy. Following initiation of inclisiran, lipids were assessed at 1 week, and at 1, 2, and 3 months. Changes in serum levels of LDL–cholesterol are shown in Figure 2. Reduction in LDL–cholesterol was seen as early as week 1. The mean percentage reduction in LDL–cholesterol at 1 month was 50% in patients not receiving statin therapy and 40% in those receiving a statin. The greatest reduction in LDL–cholesterol was seen in patients receiving combined therapy with a statin and ezetimibe. There was a clear reduction in LDL–cholesterol regardless of the type of statin and dosage. All patients receiving combined therapy with a statin reached their lipid target within 1 week after the start of treatment. No adverse effects were observed in any patient. From these preliminary observations, in a real–life setting therapy with inclisiran therapy appears to be safe and effective in lowering LDL–cholesterol in patients with high cardiovascular risk, especially when given in combination with a statin.