Polygenic Risk Driven Pragmatic Statin Trial for Heart Disease Prevention

The Pragmatic EE-PRS Trial Assessing Polygenic Risk Driven Statin Therapy for Cardiovascular Disease Prevention

This research investigates the potential advantages of intensive preventive statin treatment for healthy men aged 45-80 and women aged 55-80 who possess a high genetic predisposition to coronary artery disease (CAD). By specifically targeting the top 20% of individuals with elevated CAD polygenic risk scores (PRS), the study seeks to find out whether this tailored approach can notably decrease the occurrence of cardiovascular disease and mortality over a five-year period when compared with usual care. Despite the potential of PRS in pinpointing individuals at heightened risk for cardiovascular disease, there is a lack of focused and prospective investigations in existing research. This study aims to bridge this gap by examining whether preventive statin therapy for individuals with high CAD PRS is not only effective in diminishing cardiovascular events but also economically viable. The comparison between the statin treatment arm and standard care practice is conducted in a pragmatic manner at the primary care level.

Inclusion Criteria:

• Men aged 45-80 on 1 January 2025
• Women aged 55-80 on 1 January 2025
• CAD PRS top 20% confirmed by the Estonian Biobank (we intend to sample top 15% PRS individuals but we might have to also include 15-20% PRS individuals to fulfil the required sample size)
• The family physician of the study participant has been contracted to participate in the trial
• Written informed consent has been provided to participate in the trial

Exclusion Criteria:

• Diagnosed with ischemic heart disease (I20-I25), stroke or transient ischemia (I60-64, I69, G45), peripheral vascular occlusion (I65-66, I67.2, I70, I73.9), diseases of liver (K70-K77), end stage renal disease (N18.0), mental and behavioural disorders due to psychoactive substance use (F10-F19).

  -- The diagnosis must be present at least 2 times on a health claim or prescription within at least a 6-month period between 1.01.2022-31.12.2024.

• Currently using statin treatment:

  • The individual has at least 1 prescription from ATC groups C10AA or C10BA between 01.01.2022- 31.12.2024.
  • The individual has answered in the recruitment call that he/she is currently using statins or has been prescribed statins in the past 3 years.

• Has familiar hypercholesterolemia (APOB, PCSK9, LDLR genes verified by the Estonian biobank)

• Is currently participating in other clinical trials.

• Has been taking investigative trial medication during the past 30 days prior to study inclusion.

• Co-morbid physical or mental illnesses that prevent the individual from granting consent or participating in the trial (according to the judgement of the investigator).

• Individuals taking:

  • a combination of sofosbuvir/velpatasvir/voxilaprevir (used to treat hepatitis C);
  • ciclosporin
  • fusidic acid orally or by injection.

• Individuals with a substance abuse disorder (alcohol, narcotic substances).

• Individuals with hypersensitivity to the active substance (rosuvastatin or atorvastatin) or its excipients.