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Active, Not Recruiting

NCT Number: NCT06820086

Polygenic Risk Driven Pragmatic Statin Trial for Heart 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.

Active, Not Recruiting

This study is active but is not currently recruiting participants.

Key information

Conditions

PRS-based Primary Prevention of CVD Disease Attributes Disease Susceptibility Genetic Predisposition to Disease Genetic Risk Score Pathologic Processes Pathological Conditions, Signs and Symptoms

Age range

45 year–80 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 4

Primary location

North Estonia Medical Centre, Tallinn, Harju, Estonia

Loading trial locations.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

Rosuvastatin 20mg

Drug

Preventive statin treatment with rosuvastatin 20mg, 1 tablet per day, for healthy individuals with top 20% CAD PRS.

Primary outcomes

  1. Time to the first occurrence of Major Adverse Cardiovascular Events (MACE).

    Time frame: From enrollment to three years after the end of treatment.

    Time to the first occurrence of Major Adverse Cardiovascular Events (MACE), ICD-10 codes: ischaemic heart disease (I20-I25), stroke or transient ischemia (I60-64, I69, G45), peripheral vascular occlusion (I65-66, I67.2, I70, I73.9), revascularization (Z95.1, Z95.5, Z95.8, Z95.9) or cardiovascular death (I00-78) from baseline.

Secondary outcomes

  1. Incidence rate of death from any cause among the study participants

    Time frame: From enrollment to three years after the end of treatment.

  2. Difference in CVD risk factors from baseline by the end of the trial in the intervention and control arm;

    Time frame: From enrollment to the end of treatment at 5 years.

    Difference in CVD risk factors from baseline (LDL-cholesterol, blood pressure, BMI, waist circumference, smoking, alcohol consumption prevalence) by the end of the trial comparing the intervention and control arm;

  3. Treatment adherence in the intervention arm.

    Time frame: From enrollment to the end of treatment at 5 years.

    Treatment adherence in the intervention arm based on prescriptions and purchases of statins (C10AA, C10BA) and self-reporting using the MARS-5 scale

  4. Fidelity of intervention implementation.

    Time frame: From enrollment to the end of treatment at 5 years.

    Intervention fidelity will be calculated as a composite score by combining adherence rates (proportion of prescribed activities completed) and participant feedback (average satisfaction and engagement ratings from online questionnaires).

  5. Acceptability of the primary prevention program across study participants measured using an online questionnaire assessing satisfaction, perceived relevance, and ease of participation.

    Time frame: From first study visit to the end of treatment at 5 years.

  6. Satisfaction with study processes and results measured using an online questionnaire assessing satisfaction, perceived relevance, and ease of participation.

    Time frame: From study enrollment to the end of treatment at 5 years.

  7. Difference in plasma concentrations of rosuvastatin.

    Time frame: From enrollment to month 3 of treatment.

    Difference in plasma concentrations of rosuvastatin comparing study participants with and without a mutation in the SLCO1B1, ABCG2, CYP2C9, CYP2C19, UGT-d, SLCO1B3, SLCO2B1, ABCC2, ABCB11 genes.

  8. Difference in rosuvastatin side effects.

    Time frame: From enrollment to the end of treatment at 5 years.

    Difference in rosuvastatin side effects between study participants with and without a mutation in the SLCO1B1, ABCG2, CYP2C9, CYP2C19, UGT-d, SLCO1B3, SLCO2B1, ABCC2, ABCB11 genes.

  9. Number of participants with adverse events and serious adverse events from statin therapy.

    Time frame: From enrollment to the end of treatment at 5 years.

  10. Utilisation of healthcare resources evaluated through a cost-utilty model

    Time frame: From enrollment to the end of treatment at 5 years.

    Data on healthcare resource utilization, including non-trial physician and cardiologist visits, hospitalizations, length of stay, informal care, and direct healthcare costs, will be aggregated to develop a cost-utility model.

  11. Number of participants who withdrew or dropped out from the study.

    Time frame: From enrollment to the end of treatment at 5 years.

  12. Utilities from the EQ-5L-5D surveys and productivity costs from the iPCQ survey for calculating quality-adjusted life years (QALY) gained over a lifetime, incremental cost-effectiveness ratio (ICER).

    Time frame: From enrollment to the end of treatment at 5 years.

Other outcomes

  1. Association between gut microbiome composition and functionality and statin side effect occurrence

    Time frame: From enrollment to three years after the end of treatment.

    Logistic regression models will assess the association between CLR-transformed abundances of microbial species (profiled via MetaPhlAn4) and gene families (profiled via HUMAnN 3.0), Shannon diversity index, observed species count, and UniRef90 gene family count at baseline and after treatment initiation, and the likelihood of experiencing statin side effects. Species and gene families prevalent in >5% of samples will be included; zero-imputation applied before CLR transformation.

  2. Change from baseline in gut microbiome composition and functionality in statin vs. control arm

    Time frame: From enrollment to three years after the end of treatment.

    Changes in Shannon diversity index, observed species count, UniRef90 gene family count, and CLR-transformed abundances of microbial species (MetaPhlAn4) and gene families (HUMAnN 3.0) will be analyzed using repeated measures ANOVA adjusted for sex, age at baseline, and baseline BMI. Means and SDs will be reported for both arms at baseline and after treatment initiation.

  3. Association between baseline gut microbiome composition and functionality and statin treatment efficacy

    Time frame: From enrollment to three years after the end of treatment.

    Linear models adjusted for sex, age at baseline, and baseline BMI will assess the association between baseline Shannon diversity index, observed species count, UniRef90 gene family count, and CLR-transformed abundances of microbial species (MetaPhlAn4) and gene families (HUMAnN 3.0), and statin treatment efficacy. Species and gene families prevalent in >5% of samples will be included.

Sponsors and collaborators

Lead sponsor

Mikk JÜRISSON

Other

Collaborators

  • European Union
  • North Estonian Medical Center
  • Tartu University Hospital
  • The Estonian Health Insurance Fund

Registry information

Official study title

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

Acronym: EE-PRS

Important dates

Study start
2025
Primary completion
2031
Study completion
2034
First posted
Feb 11, 2025
Registry last updated
May 13, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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