Polygenic Risk Driven Pragmatic Statin Trial for Heart Disease Prevention

Phase 4Enrolling By InvitationNCT06820086

Mikk JÜRISSON2,500 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

PREVENTION

Masking

NONE

Enrollment

2,500

Conditions

PRS-based Primary Prevention of CVD

Interventions

Eligibility

Sex: ALLMin age: 45 YearsMax age: 80 Years

Medical Language ↔ Plain English

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.

Outcomes

Primary Outcomes

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

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.

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

Secondary Outcomes

Incidence rate of death from any cause among the study participants

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

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

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

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

Treatment adherence in the intervention arm.

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

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

Fidelity of intervention implementation.

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).

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

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.

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.

Difference in plasma concentrations of rosuvastatin.

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.

Time frame: From enrollment to month 3 of treatment.

Difference in rosuvastatin side effects.

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.

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

Utilisation of healthcare resources evaluated through a cost-utilty model

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.

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

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.

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

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

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.

Polygenic Risk Driven Pragmatic Statin Trial for Heart Disease Prevention

Overview

Conditions

Interventions

Eligibility

Locations (2)

Outcomes

Primary Outcomes

Secondary Outcomes