Evidence map›Paper›PMID 25748612›Full record

SynthesisLancet (London, England)2015

Genetic risk, coronary heart disease events, and the clinical benefit of statin therapy: an analysis of primary and secondary prevention trials.

J L Mega, N O Stitziel, J G Smith, D I Chasman, M Caulfield, J J Devlin, F Nordio, C Hyde, C P Cannon, F Sacks and 7 more

5 registry-linked trialsAbstract readMeta-Analysis
PubMed Full text at PMC Publisher
In one paragraph

Synthesis in Lancet (London, England), 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 5 registered trials, which are not on this map. Cited by 335 papers, 5 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
335citing papers in PubMed, 5 pooled it
–field-weighted citation impact
1 · What the graph read from 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.

2 · The registry

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.

NCT04636996 naunknown statusnot on this mapstarted 2021, after this paper: background citation

Effects of Artificial Intelligence Assisted Follow-up Strategy Based on a New Remote Contactless Sleep Monitoring System on Secondary Prevention in Patients Received Coronary Artery Bypass Grafting Surgery

TypeinterventionalSponsorChinese Academy of Medical Sciences, Fuwai HospitalRan2021 to 2022Enrolled200ConditionsCoronary Heart Disease, Artificial Intelligence, Sleep ApneaArmsartificial intelligence assisted follow-up
NCT05072275 unknown statusnot on this mapstarted 2023, after this paper: background citation

Prospective Electronic Polygenic Risk Study (PEPRS) - First Phase

TypeobservationalSponsorScripps Translational Science InstituteRan2023 to 2023Enrolled1,000ConditionsCoronary Artery Disease
NCT05175651 nanot yet recruitingnot on this mapstarted 2023, after this paper: background citation

Prospective Electronic Polygenic Risk Study - Second Phase

TypeinterventionalSponsorScripps Translational Science InstituteRan2023 to 2027Enrolled10,000ConditionsCoronary Artery Disease, GlaucomaArmsGenetic risk assessment
NCT05277116 naactive not recruitingnot on this mapstarted 2022, after this paper: background citation

The Electronic Medical Records and GEnomics (eMERGE) Network Genomic Risk Assessment

TypeinterventionalSponsorVanderbilt University Medical CenterRan2022 to 2030Enrolled26,877ConditionsGenetic DiseaseArmsGenome Informed Risk Assessment (GIRA) report
NCT07039123 naactive not recruitingnot on this mapstarted 2025, after this paper: background citation

Polygenic Risk Score to Optimize Primary Prevention in Intermediate Risk Population (PERSONAL)

TypeinterventionalSponsorUniversity of BernRan2025 to 2027Enrolled205ConditionsPrimary Prevention of Cardiovascular DiseaseArmsPolygenic Risk Score for Coronary Artery Disease (PRS-CAD), Standardized Risk Communication Tool (SCORE2)
3 · Its place in the literature

Who cites it

335 citing papers in PubMed, 5 syntheses or guidelines pooled it.

  1. Pooled it
  2. Pooled it
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  6. Polygenic risk, aspirin, and primary prevention of coronary artery disease.European heart journal. Cardiovascular pharmacotherapy · 2025
    Trial
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  9. Review
  10. Article
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  12. Polygenic Prediction of Nongoal Response to Statin Therapy.Circulation. Genomic and precision medicine · 2026
    Article
  13. Review
  14. Article
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275 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

17 authors.

J L Mega *TIMI Study Group, Cardiovascular Division, Brigham and Women's Hospital and Harvard Medical School, Boston, MA.
N O Stitziel *Cardiovascular Division, Department of Medicine and Division of Statistical Genomics, Washington University School of Medicine, Saint Louis, MO.
J G SmithDepartment of Cardiology, Clinical Sciences, Lund University and Skåne University Hospital, Lund, Sweden.
D I ChasmanCenter for Cardiovascular Disease Prevention, Divisions of Preventive Medicine and Genetics, Brigham and Women's Hospital and Harvard Medical School, Boston, MA.
M CaulfieldWilliam Harvey Research Institute, Queen Mary University of London and Barts NIHR CV Biomedical Research Institute, London, United Kingdom.
J J DevlinQuest Diagnostics, Alameda, CA.
F NordioTIMI Study Group, Cardiovascular Division, Brigham and Women's Hospital and Harvard Medical School, Boston, MA.
C HydePfizer Research Laboratory, Groton, CT.
C P CannonTIMI Study Group, Cardiovascular Division, Brigham and Women's Hospital and Harvard Medical School, Boston, MA.
F SacksDepartment of Nutrition, Harvard School of Public Health and Channing Division of Network Medicine, Brigham and Women's Hospital, Boston, MA.
N PoulterInternational Centre for Circulatory Health, National Heart & Lung Institute, Imperial College London, United Kingdom.
P SeverInternational Centre for Circulatory Health, National Heart & Lung Institute, Imperial College London, United Kingdom.
P M RidkerCenter for Cardiovascular Disease Prevention, Divisions of Preventive Medicine and Cardiology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA.
E BraunwaldTIMI Study Group, Cardiovascular Division, Brigham and Women's Hospital and Harvard Medical School, Boston, MA.
O MelanderDepartment of Clinical Sciences, Faculty of Medicine, Lund University and Department of Internal Medicine, Skåne University Hospital, Malmö, Sweden.
S Kathiresan *Program in Medical and Population Genetics, Broad Institute of Harvard and MIT; Center for Human Genetic Research and Cardiovascular Research Center, Massachusetts General Hospital and Harvard Medical School, Boston, MA.
M S Sabatine *TIMI Study Group, Cardiovascular Division, Brigham and Women's Hospital and Harvard Medical School, Boston, MA.

Funding

Using genetic variation to study biology of blood lipids & coronary heart diseaseR01HL127564 · NHLBI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Pradeep Natarajan, Gina Marie Peloso · 2015 to 2026
$7.3M
Antiplatelet Therapy: Platelet Inhibition, Polymorphisms, and Protein BiomarkersR01HL098082 · NHLBI · BRIGHAM AND WOMEN'S HOSPITAL · PI SABATINE, MARC S · 2009 to 2012
$1.8M
Genetic Risk Stratification to Identify Individuals for Early Statin TherapyRC1HL099634 · NHLBI · BRIGHAM AND WOMEN'S HOSPITAL · PI SABATINE, MARC S · 2009 to 2010
$993k
Rare coding variation and risk for myocardial infarctionK08HL114642 · NHLBI · WASHINGTON UNIVERSITY · PI STITZIEL, NATHAN OLIVER · 2012 to 2016
$703k
Medical Research Council G9521010Medical Research Council MR/K006584/1NHLBI NIH HHS K08 HL114642NHLBI NIH HHS R01 HL098082NHLBI NIH HHS R01 HL127564NHLBI NIH HHS RC1 HL099634
6 · The paper itself

Abstract

backgroundGenetic variants have been associated with the risk of coronary heart disease. In this study, we tested whether or not a composite of these variants could ascertain the risk of both incident and recurrent coronary heart disease events and identify those individuals who derive greater clinical benefit from statin therapy.

methodsA community-based cohort study (the Malmo Diet and Cancer Study) and four randomised controlled trials of both primary prevention (JUPITER and ASCOT) and secondary prevention (CARE and PROVE IT-TIMI 22) with statin therapy, comprising a total of 48,421 individuals and 3477 events, were included in these analyses. We studied the association of a genetic risk score based on 27 genetic variants with incident or recurrent coronary heart disease, adjusting for traditional clinical risk factors. We then investigated the relative and absolute risk reductions in coronary heart disease events with statin therapy stratified by genetic risk. We combined data from the different studies using a meta-analysis.

findingsWhen individuals were divided into low (quintile 1), intermediate (quintiles 2-4), and high (quintile 5) genetic risk categories, a significant gradient in risk for incident or recurrent coronary heart disease was shown. Compared with the low genetic risk category, the multivariable-adjusted hazard ratio for coronary heart disease for the intermediate genetic risk category was 1·34 (95% CI 1·22-1·47, p<0·0001) and that for the high genetic risk category was 1·72 (1·55-1·92, p<0·0001). In terms of the benefit of statin therapy in the four randomised trials, we noted a significant gradient (p=0·0277) of increasing relative risk reductions across the low (13%), intermediate (29%), and high (48%) genetic risk categories. Similarly, we noted greater absolute risk reductions in those individuals in higher genetic risk categories (p=0·0101), resulting in a roughly threefold decrease in the number needed to treat to prevent one coronary heart disease event in the primary prevention trials. Specifically, in the primary prevention trials, the number needed to treat to prevent one such event in 10 years was 66 in people at low genetic risk, 42 in those at intermediate genetic risk, and 25 in those at high genetic risk in JUPITER, and 57, 47, and 20, respectively, in ASCOT.

interpretationA genetic risk score identified individuals at increased risk for both incident and recurrent coronary heart disease events. People with the highest burden of genetic risk derived the largest relative and absolute clinical benefit from statin therapy.

fundingNational Institutes of Health.

Indexed as

Coronary DiseaseHumansHydroxymethylglutaryl-CoA Reductase InhibitorsNumbers Needed To TreatPrimary PreventionRecurrenceRisk AssessmentSecondary PreventionTreatment OutcomeHydroxymethylglutaryl-CoA Reductase Inhibitors

Identifiers

PMID25748612
PMCPMC4608367

What Socratic holds

Textmetadata
LicenceTDM
Read underepoch 390

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 Socratic graph.