Trial reportCirculation. Cardiovascular genetics2014
High-dose simvastatin exhibits enhanced lipid-lowering effects relative to simvastatin/ezetimibe combination therapy.
Trial report in Circulation. Cardiovascular genetics, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
10 citing papers in PubMed, 18 citations in OpenAlex.
- Cardiometabolic Factor-Specific Metabolic Signatures in Metabolic Dysfunction-Associated Steatotic Liver Disease: Insights from Non-Targeted Metabolomics.Antioxidants (Basel, Switzerland) · 2026Article
- A Reproducible Ceramide Phenotype of Sepsis Across Aetiologies - A Monocenter Cohort Study.Journal of inflammation research · 2026Article
- The Role of Statins in the Prevention of Ovarian and Endometrial Cancers.Cancer prevention research (Philadelphia, Pa.) · 2023Article
- Discovery of drug-omics associations in type 2 diabetes with generative deep-learning models.Nature biotechnology · 2023Article
- Modulation of Plasma Lipidomic Profiles in Metastatic Castration-Resistant Prostate Cancer by Simvastatin.Cancers · 2022Article
- Similar plasma lipidomic profile in people living with HIV treated with a darunavir-based or an integrase inhibitor-based antiretroviral therapy.Scientific reports · 2019Article
- Effects of Silymarin on the In Vivo Pharmacokinetics of Simvastatin and Its Active Metabolite in Rats.Molecules (Basel, Switzerland) · 2019Article
- Complex polymorphisms in endocytosis genes suggest alpha-cyclodextrin as a treatment for breast cancer.PloS one · 2018Article
- Applying metabolomics to cardiometabolic intervention studies and trials: past experiences and a roadmap for the future.International journal of epidemiology · 2016Review
- Lovastatin reversed the enhanced sphingomyelin caused by 27-hydroxycholesterol in cultured vascular endothelial cells.Biochemistry and biophysics reports · 2016Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
12 authors at 4 institutions in 2 countries.
Funding
Abstract
Statins are the frontline in cholesterol reduction therapies; however, their use in combination with agents that possess complimentary mechanisms of action may achieve further reductions in low-density lipoprotein cholesterol. Thirty-nine patients were treated with either 80 mg simvastatin (n=20) or 10 mg simvastatin plus 10 mg ezetimibe (n=19) for 6 weeks. Dosing was designed to produce comparable low-density lipoprotein cholesterol reductions, while enabling assessment of potential simvastatin-associated pleiotropic effects. Baseline and post-treatment plasma were analyzed for lipid mediators (eg, eicosanoids and endocannabinoids) and structural lipids by liquid chromatography tandem mass spectrometry. After statistical analysis and orthogonal projections to latent structures multivariate modeling, no changes were observed in lipid mediator levels, whereas global structural lipids were reduced in response to both monotherapy (R(2)Y=0.74; Q(2)=0.66; cross-validated ANOVA P=7.0×10(-8)) and combination therapy (R(2)Y=0.67; Q(2)=0.54; cross-validated ANOVA P=2.6×10(-5)). Orthogonal projections to latent structures modeling identified a subset of 12 lipids that classified the 2 treatment groups after 6 weeks (R(2)Y=0.65; Q(2)=0.61; cross-validated ANOVA P=5.4×10(-8)). Decreases in the lipid species phosphatidylcholine (15:0/18:2) and hexosyl-ceramide (d18:1/24:0) were the strongest discriminators of low-density lipoprotein cholesterol reductions for both treatment groups (q<0.00005), whereas phosphatidylethanolamine (36:3e) contributed most to distinguishing treatment groups (q=0.017). Shifts in lipid composition were similar for high-dose simvastatin and simvastatin/ezetimibe combination therapy, but the magnitude of the reduction was linked to simvastatin dosage. Simvastatin therapy did not affect circulating levels of lipid mediators, suggesting that pleiotropic effects are not associated with eicosanoid production. Only high-dose simvastatin reduced the relative proportion of sphingomyelin and ceramide to phosphatidylcholine (q=0.008), suggesting a pleiotropic effect previously associated with a reduced risk of cardiovascular disease.
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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.