The Pragmatic EE-PRS Trial Assessing Polygenic Risk Driven Statin Therapy for Cardiovascular Disease Prevention
试验速览
- 阶段
- 4 期
- 状态
- 进行中（未招募）
- 发起方
- 入组人数
- 2,714
- 试验地点
- 2
- 主要终点
- Time to the first occurrence of Major Adverse Cardiovascular Events (MACE).
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- None
入排标准
- 年龄范围
- 45 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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.
- •Currently using statin treatment:
- •The individual has at least 1 prescription from ATC groups C10AA or C10BA between 01.01.2022- 31.12.
- •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.
研究组 & 干预措施
Control arm
Control arm participants (n=1350) comprise healthy men aged 45- 80 years and women aged 55-80 years with a high (top 20%) coronary artery disease (CAD) polygenic risk score.
Participants in the control arm of the trial will be following regular primary care as their family doctors will not be informed of their patients' participation in the trial. This means that in the control arm real-life primary care activities will take place including potential cholesterol-lowering treatment based on the current treatment and prevention guidelines. At the end of the trial, physicians will be informed about their patients who were in the control arm for scheduling a final study visit and ordering a blood test. During the final trial visit the physicians will inform participants of their CAD PRS, provide counselling and take final measurements.
Intervention arm receiving statin treatment
Intervention arm participants (n=1350) comprise healthy men aged 45- 80 years and women aged 55-80 years with a high (top 20%) coronary artery disease (CAD) polygenic risk score.
They are prescribed by their primary care physician the trial medication, rosuvastatin 20mg, 1 tablet per day, for the entire duration of the trial. Intervention arm participants will be measured and regular blood analyses will be taken throughout the trial. They will be having regular primary care visits with their family physician and telemedicine visits with study nurses.
干预措施: Rosuvastatin 20mg (Drug)
结局指标
主要结局
Time to the first occurrence of Major Adverse Cardiovascular Events (MACE).
时间窗: 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.
次要结局
- Treatment adherence in the intervention arm.(From enrollment to the end of treatment at 5 years.)
- Utilisation of healthcare resources evaluated through a cost-utilty model(From enrollment to the end of treatment at 5 years.)
- Number of participants with adverse events and serious adverse events from statin therapy.(From enrollment to the end of treatment at 5 years.)
- Fidelity of intervention implementation.(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.(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.(From study enrollment to the end of treatment at 5 years.)
- Difference in plasma concentrations of rosuvastatin.(From enrollment to month 3 of treatment.)
- Difference in rosuvastatin side effects.(From enrollment to the end of treatment at 5 years.)
- Number of participants who withdrew or dropped out from the study.(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).(From enrollment to the end of treatment at 5 years.)
- Incidence rate of death from any cause among the study participants(From enrollment to three years after the end of treatment.)
- Difference in CVD risk factors from baseline by the end of the trial in the intervention and control arm;(From enrollment to the end of treatment at 5 years.)
研究者
Mikk JÜRISSON
Associate professor of Public Health
University of Tartu