Pragmatic trial assessing polygenic risk driven statin therapy for cardiovascular disease prevention: study protocol for the EE-PRS trial.

INTRODUCTION

Atherosclerotic cardiovascular disease (ASCVD) continues to be a leading cause of preventable death globally. Polygenic risk scores (PRS) offer a way to detect individuals at higher relative risk of developing ASCVD, but they have not yet been incorporated into routine clinical practice. Pragmatic trials offer a way to evaluate the integration of PRS into cardiovascular disease prevention in primary care, allowing for a more accurate assessment of their effectiveness in everyday clinical practice.

METHODS AND ANALYSIS: This trial evaluates the effectiveness of preventive statin treatment on reducing the incidence of cardiovascular events and death over 5 years in women (aged 55-80) and men (aged 45-80) with a high coronary artery disease PRS. This is a pragmatic, multicentre, open-label, parallel group, randomised clinical trial with a 1:1 allocation ratio to intervention (n=1350), receiving preventive rosuvastatin 20 mg treatment or control (n=1350), receiving current standard of care. Following the intention-to-treat principle, all randomised participants are analysed according to their allocated group, with the primary outcome defined as time to first major adverse cardiovascular event, comprising ischaemic heart disease, stroke or transient ischaemia, peripheral vascular occlusion and stenosis, revascularisation or cardiovascular death.

ETHICS AND DISSEMINATION: This trial has received ethical approval from the Estonian Committee on Bioethics and Human Research (13.06.2024 nr 1.1-12/1531) and the Estonian Ethics Committee for Medicinal Products (19.12.2024 nr RKU-4/92).

TRIAL REGISTRATION NUMBER: NCT06820086.