Impact of PCSK9 inhibitors on the quality of life of patients at high cardiovascular risk

Lowering low-density lipoprotein cholesterol (LDL-C) is a critical intervention to contrast cardiovascular risk. In both primary and secondary prevention, the reduction of LDL-C levels with statin and non-statin agents correlates linearly with a decreased risk of cardiovascular events. Recent European Guidelines recommend an LDL-C goal of <100mg/dL or <70mg/dL in patients at high or very high cardiovascular risk, respectively. Combining PCSK9 inhibitors (PCSK9is) with statins and/or ezetimibe provides a relevant prognostic benefit in high-risk patients, especially in those not reaching recommended targets despite maximally tolerated statin dose. Over the last years, data regarding health-related quality of life (HRQOL) and qualityadjusted life years has been increasingly taken into consideration to support medical decisions in clinical practice. For this purpose, the European Quality of Life (EuroQol) Group, a research network dedicated to the study of health status, developed the EQ-5D questionnaire. This questionnaire has been validated in different populations, languages and clinical settings, enabling a standard comparison of HRQOL. While traditional lipid-lowering medications showed a positive impact on patients’ quality of life (QoL), a more invasive lipid-lowering regimen (i.e. lipoprotein apheresis), can adversely affect perceived QoL. To date, no studies have investigated QoL according to the EQ-5D in patients treated with PCSK9i. This study aimed to evaluate the impact of PCSK9i on the QoL of patients at high or very high cardiovascular risk. In this prospective single-centre study, we evaluated patients at high or very high cardiovascular risk admitted to our Academic Cardiology Centre. Patients were categorized as high or very high cardiovascular risk in accordance with the definition proposed by the 2016 European Guidelines on Cardiovascular Disease Prevention in Clinical Practice and the European Systematic Coronary Risk Evaluation (SCORE) system. Patients who did not reach recommended LDL-C goals despite maximal tolerated lipid-lowering therapy with statins and ezetimibe were treated additionally with evolocumab 140mg or alirocumab 75mg bi-weekly, according to national regulations. We measured the health status perceived by patients through the self-administered EuroQoL (or EQ-5D-3L) in the Italian language at enrolment (shortly prior to starting PCSK9 inhibitors therapy) and at oneyear follow-up. The EuroQol consists of two sections. The first part consists of five items exploring the current state of health of the respondent with different levels of severity. The five items comprise five dimensions (mobility, self-care, usual activities, pain/discomfort, anxiety/ depression) and each domain consists of five severity levels (no problems, slight problems, moderate problems, severe problems, extreme problems). An algorithm for an Italian population allows the calculation of a final EQ-5D score based on the assignment of weights for each answer. The second part consists of a 100-point score numeric visual analogue scale (VAS) for perceived health status. All participants provided written informed consent. All statistical analyses (Wilcoxon test for non-continuous variables and t-test for continuous variables) were performed using SPSS 25.0 (Chicago, USA).