Pleiotropic effects of inclisiran on arterial structural and functional parameters

Abstract Background and objectives Inclisiran is the latest PCSK9 inhibitor available for reducing LDL-cholesterol. Its effects on arterial structural and functional properties are not yet known. The purpose of our study is to longitudinally evaluate these properties in patients starting therapy with this new drug for dyslipidemia. Methods Prospective longitudinal study enrolling all patients who started Inclisiran therapy at our hospital. Inclisiran injections were administered at T0, after 3 months and then every 6 months. Carotid-femoral Pulse Wave Velocity (PWV), carotid Intima Media Thickness (IMT) and brachial Flow Mediated Dilation (FMD) were evaluated before the first injection, after 6 months (T1) and after 1 year (T2). Data from 15 patients at 1 year were analyzed. Results The mean age was 69±7.1 years, 72.7% of the subjects were men and the basal LDL-C was 102.7±49.6 mg/dL, while BP was 140.6±13.3/79.1±6.1 mmHg. 90.9% of patients were in secondary prevention (acute or chronic coronary syndrome). 86.4% were on high-intensity statin therapy and 81.8% on ezetimibe. At the 1 year’s evaluation, a significant reduction of LDL-C (49.3±16.4 mg/dL, p0.001) and BP (126.9±10.1/71.2±6.5 mmHg, p0.001) was observed. Among the arterial biomarkers, only PWV showed a significant reduction (from 10.9±2.0 to 9.8±1.4 m/s, p0.001) while the changes in IMT (from 705.9±151.3 to 696.0±202.1 μm, p=0.333) and FDM (from 7.5±8.9 a 6.9±8.0%, p=0.449) were not statistically significant. Conclusions Inclisiran has been confirmed as an excellent LDL-C lowering drug that also significantly reduces PWV. Studies with a larger number of patients are needed to confirm our findings.