Trial reportCirculation2020
Predicting Benefit From Evolocumab Therapy in Patients With Atherosclerotic Disease Using a Genetic Risk Score: Results From the FOURIER Trial.
Trial report in Circulation, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. It is linked to trial NCT07039123 (Polygenic Risk Score to Optimize Primary Prevention in Intermediate Risk Population), which is not on this map. Cited by 122 papers, 5 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Polygenic Risk Score to Optimize Primary Prevention in Intermediate Risk Population (PERSONAL)
Who cites it
122 citing papers in PubMed, 5 syntheses or guidelines pooled it.
- Discovery and systematic characterization of risk variants and genes for coronary artery disease in over a million participants.Nature genetics · 2022Pooled it
- Pooled it
- Higher polygenic risk for melanoma is associated with improved survival in a high ultraviolet radiation setting.Journal of translational medicine · 2022Pooled it
- A polygenic risk score improves risk stratification of coronary artery disease: a large-scale prospective Chinese cohort study.European heart journal · 2022Pooled it
- The Effect of PCSK9 (Proprotein Convertase Subtilisin/Kexin Type 9) Inhibition on the Risk of Venous Thromboembolism.Circulation · 2020Pooled it
- Polygenic Risk Based Detection and Treatment of Subclinical Coronary Atherosclerosis in the PROACT Clinical Trials.Journal of the American College of Cardiology · 2026Trial
- Interactions of blood biomolecules with early rhythm control in atrial fibrillation patients: exploratory analysis of the EAST-AFNET 4 biomolecule study.Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology · 2026Trial
- Polygenic risk, aspirin, and primary prevention of coronary artery disease.European heart journal. Cardiovascular pharmacotherapy · 2025Trial
- Association of genetic risk and outcomes in patients with atrial fibrillation: interactions with early rhythm control in the EAST-AFNET4 trial.Cardiovascular research · 2023Trial
- Pharmacogenomics polygenic risk score for drug response prediction using PRS-PGx methods.Nature communications · 2022Trial
- Genetic and clinical risk factors for recurrent events among patients with coronary artery disease.American journal of preventive cardiology · 2026Article
- Development and Validation of a Clinical Polygenic Risk Report in U.S.-Based Health Systems for 8 Cardiovascular Conditions.Journal of the American College of Cardiology · 2026Article
- Inherited risk of coronary artery disease: redefining care with imaging and genetics.Nature reviews. Cardiology · 2026Review
- Polygenic Prediction of Nongoal Response to Statin Therapy.Circulation. Genomic and precision medicine · 2026Article
- Translating genome-wide association studies at multiple scales: Drug target prioritization, cellular architectures, and organ imaging.Cell genomics · 2026Review
- Improving Polygenic Risk Prediction for Atherosclerotic Cardiovascular Disease in East Asian Populations.JACC. Asia · 2026Review
- Genetically Informed Research Designs in Perinatal Pharmacoepidemiology: A Methodological Overview.Drug safety · 2026Review
- An introduction to polygenic scores - methodological basics and recent advances.Medizinische Genetik : Mitteilungsblatt des Berufsverbandes Medizinische Genetik e.V · 2026Article
- Polygenic risk scores in clinical applications - opportunities and challenges.Medizinische Genetik : Mitteilungsblatt des Berufsverbandes Medizinische Genetik e.V · 2026Article
- Selphi, a tool for improving genotype imputation accuracy.Scientific reports · 2026Article
62 more citing papers are in PubMed but not listed here.
Corrections and comments
- Commented on by
- Erratum issued
Authors and funding
15 authors.
Funding
Abstract
backgroundThe ability of a genetic risk score to predict risk in established cardiovascular disease and identify individuals who derive greater benefit from PCSK9 (proprotein convertase subtilisin/kexin type 9) inhibition has not been established.
methodsWe studied 14 298 patients with atherosclerotic cardiovascular disease from the FOURIER trial (Further Cardiovascular Outcomes Researh With PCSK9 Inhibition in Subjects With Elevated Risk). A 27-single-nucleotide polymorphism genetic risk score defined low (quintile 1), intermediate (quintiles 2-4), and high (quintile 5) genetic risk. Patients were also categorized by major atherosclerotic risk factors including diabetes mellitus, hypertension, low-density lipoprotein cholesterol ≥100 mg/dl, and smoking; multiple (≥2) risk factors was considered high clinical risk. Outcomes consisted of major coronary events (coronary heart death, myocardial infarction, or coronary revascularization) and major vascular events (major coronary events and ischemic stroke). Median follow-up was 2.3 years.
resultsAfter we adjusted for clinical factors, the genetic risk score was associated with risk for both major vascular events (
conclusionPatients without multiple clinical risk factors or high genetic risk had a low event rate and did not appear to derive benefit from evolocumab over 2.3 years. Conversely, patients with multiple clinical risk factors but without high genetic risk had intermediate risk and intermediate risk reduction. Patients with high genetic risk, regardless of clinical risk, had a high event rate and derived the greatest relative and absolute benefit from evolocumab, which mitigated this risk.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.