Trial reportEuropean heart journal2013
Impact of common genetic variation on response to simvastatin therapy among 18 705 participants in the Heart Protection Study.
Trial report in European heart journal, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers, 10 of them syntheses that pooled it.
What it found
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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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
50 citing papers in PubMed, 10 syntheses or guidelines pooled it, 109 citations in OpenAlex.
- APOE genotype and the effect of statins on lipid outcomes: A meta-analysis.British journal of clinical pharmacology · 2026Pooled it
- Association Between ABCG2 Polymorphism and Statin-Induced Adverse Events: A Meta-Analysis.Cardiovascular toxicology · 2025Pooled it
- Genomewide Association Study of Statin-Induced Myopathy in Patients Recruited Using the UK Clinical Practice Research Datalink.Clinical pharmacology and therapeutics · 2019Pooled it
- LPA Variants Are Associated With Residual Cardiovascular Risk in Patients Receiving Statins.Circulation · 2018 · on this mapPooled it
- A genetic risk score is associated with statin-induced low-density lipoprotein cholesterol lowering.Pharmacogenomics · 2016Pooled it
- Genetic risk, coronary heart disease events, and the clinical benefit of statin therapy: an analysis of primary and secondary prevention trials.Lancet (London, England) · 2015Pooled it
- Pharmacogenetic meta-analysis of genome-wide association studies of LDL cholesterol response to statins.Nature communications · 2014Pooled it
- Very low levels of atherogenic lipoproteins and the risk for cardiovascular events: a meta-analysis of statin trials.Journal of the American College of Cardiology · 2014Pooled it
- Robust association of the LPA locus with low-density lipoprotein cholesterol lowering response to statin treatment in a meta-analysis of 30 467 individuals from both randomized control trials and observational studies and association with coronary artery disease outcome during statin treatment.Pharmacogenetics and genomics · 2013 · on this mapPooled it
- The pharmacogenetics of rosuvastatin and implications for treatment: a systematic review.PharmacogenomicsPooled it
- Polymorphisms of SLCO1B1 rs4149056 and SLC22A1 rs2282143 are associated with responsiveness to acitretin in psoriasis patients.Scientific reports · 2018Trial
- Candidate-Gene Study of Functional Polymorphisms in SLCO1B1 and CYP3A4/5 and the Cholesterol-Lowering Response to Simvastatin.Clinical and translational science · 2017Trial
- Individual and Combined Associations of Genetic Variants in CYP3A4, CYP3A5, and SLCO1B1 With Simvastatin and Simvastatin Acid Plasma Concentrations.Journal of cardiovascular pharmacology · 2015Trial
- Trial
- Polygenic Prediction of Nongoal Response to Statin Therapy.Circulation. Genomic and precision medicine · 2026Article
- Pharmacogenomic predictors of drug response and choice in dyslipidemia and hypertension.medRxiv : the preprint server for health sciences · 2026Article
- Leveraging large-scale biobank EHRs to enhance pharmacogenetics of cardiometabolic disease medications.Nature communications · 2025Article
- Statin therapy in primary and secondary cardiovascular disease prevention.Current atherosclerosis reports · 2024Review
- Leveraging large-scale biobank EHRs to enhance pharmacogenetics of cardiometabolic disease medications.medRxiv : the preprint server for health sciences · 2024Article
- Predictive Value ofGenes · 2023Article
Corrections and comments
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
Abstract
aimsStatins reduce LDL cholesterol (LDL-C) and the risk of vascular events, but it remains uncertain whether there is clinically relevant genetic variation in their efficacy. This study of 18 705 individuals aims to identify genetic variants related to the lipid response to simvastatin and assess their impact on vascular risk response. METHODS AND
resultsA genome-wide study of the LDL-C and apolipoprotein B (ApoB) response to 40 mg simvastatin daily was performed in 3895 participants in the Heart Protection Study, and the nine strongest associations were tested in 14 810 additional participants. Selected candidate genes were also tested in up to 18 705 individuals. There was 90% power to detect differences of 2.5% in LDL-C response (e.g. 42.5 vs. 40% reduction) in the genome-wide study and of 1% in the candidate gene study. None of the associations from the genome-wide study was replicated, and nor were significant associations found for 26 of 36 candidates tested. Novel lipid response associations with variants in LPA, CELSR2/PSRC1/SORT1, and ABCC2 were found, as well as confirmatory evidence for published associations in LPA, APOE, and SLCO1B1. The largest and most significant effects were with LPA and APOE, but were only 2-3% per allele. Reductions in the risk of major vascular events during 5 years of statin therapy among 18 705 high-risk patients did not differ significantly across genotypes associated with the lipid response.
conclusionsCommon genetic variants do not appear to alter the lipid response to statin therapy by more than a few per cent, and there were similar large reductions in vascular risk with simvastatin irrespective of genotypes associated with the lipid response to simvastatin. Consequently, their value for informing clinical decisions related to maximizing statin efficacy appears to be limited.
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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.