Effects of PCSK-9 inhibitors on arterial structure and function: preliminary results

Abstract Background One of the latest chapters in the research for new and stronger lipid lowering therapies has led to the development of PCSK9 inhibitors. In addition to the benefit on lipid profile, a limited number of studies have been published showing a possible improvement in vascular function and structure following their administration. Purpose: To evaluate the effects of PCSK9 inhibitors on structural (via carotid Intima Media Thickness – IMT) and functional (carotid–femoral Pulse Wave Velocity – cf–PWV – and brachial artery Flow Mediated Dilatation – FMD) arterial properties. Methods Twenty–two dyslipidemic patients with a clinical indication to PSCK9 inhibitors were prospectively recruited at the Cardiology Rehabilitation of ASST Grande Ospedale Metropolitano Niguarda Hospital (Milan, Italy). Anthropometric, clinical and therapeutic data were recorded. Each patient underwent instrumental examinations to assess cf–PWV, IMT and FMD at T0 (before the start of therapy), T1 (after 6 months) and T2 (after 12 months). Results In the 22 patients who reached 6 months of follow up there was a significant reduction in LDL cholesterol (from 127.8±31.7 to 47.4±29.1 mg/dl, p<0. 0001) while there was no significant difference in arterial parameters (cf–PWV: from 10.5±3.5 to 9.4±2.3 m/s, p=0.092; FMD: from 11.4±8.1 to 9.8±8.3%, p=0.407; IMT: from 775.6±192.8 to 768.7±144.7, microm, p=0.854). Similar results were also obtained in the 12 patients who reached one year of follow–up: LDL from 129.4±29.1 to 48.8±21.9 mg/dl, p<0.0001; cf–PWV from 10.4±3.3 to 10.5±2.9, p=0.874; FMD from 12.0±9.1 to 11.0±5.6%, p=0.930; IMT from 745.1±203.9 to 770.0±127.3 microm, p=0.710. Conclusion Our study confirm the strong LDL reduction with PCSK9 inhibitors that are needed in order to reach the targets set by the ESC 2019 guidelines. In contrast, they do not show a significant effect on arterial function and structure in terms of cf–PWV, FMD and carotid IMT.