P198 PRELIMINARY 30–60 DAY EVALUATION OF INCLISIRAN EFFICACY

Abstract

Abstract Background Inclisiran is a small–interfering RNA that selectively silences the hepatic synthesis of PCSK–9 protein with a two doses per year administration, increasing the availability of LDL receptors. Consequent reduction in circulating LDL levels observed in clinical trials, when associated with statin and ezetimibe therapy, is about 50%, with effect onset 14 days after the first administration. Methods This initial experience refers to three male patients with post–infarction ischemic heart disease who underwent revascularization (two with PCI, one with BPAC) one to three years previously, treated with ezetimibe 10 mg OD and high–dose atorvastatin (two with 80 mg OD, one with 40 mg OD). LDL levels were higher than recommended in patients at very high cardiovascular risk by European Society of Cardiology guidelines (mean 90 mg/dL, range 87–95). Patients were informed of the available data on Inclisiran and consented to the terms of use. Subcutaneous administration was performed by a physician in a hospital outpatient setting. Lipid values were checked on the 30th day. Results Two patients continued oral therapy and got a 58% reduction in values (mean 39 mg/dL, range 22–55). One patient, despite informed of the need to continue oral treatment, spontaneously stopped statin and ezetimibe treatment, obtaining a 30–day increase in LDL of 50% (131 vs 87 mg/dL). At the next control, 30 days after the resumption of oral therapy, the value was 44 mg/dL, with a reduction of 49% compared to baseline. No adverse events were recorded. Conclusions Data at 30–60 days on three patients treated with Inclisiran show that its addition to statin and ezetimibe treatment resulted in an average reduction in LDL cholesterol of 56% allowing the achievement of the target in 100% of cases. The favorable interaction between Inclisiran, statin and ezetimibe represents an effective strategy in patients at very high cardiovascular risk. The case of suspension of oral treatment seems to suggest a marked interaction of Inclisiran effect with statin therapy. Administration by a healthcare professional represents an opportunity for better follow–up management, allowing monitoring of therapeutic adherence and re–evaluation of concomitant therapies.