Trial reportThe New England journal of medicine2008
Intensive lipid lowering with simvastatin and ezetimibe in aortic stenosis.
Trial report in The New England journal of medicine, 2008. The graph read 3 numbers from its abstract, feeding 4 cells of the map: it finds no clear difference in 4. It is linked to 6 registered trials, which are not on this map. Cited by 510 papers, 10 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.
Aortic-valve replacement was performed in 267 patients (28.3%) in the simvastatin-ezetimibe group and in 278 patients (29.9%) in the placebo group (hazard ratio, 1.00; 95% CI, 0.84 to 1.18; P=0.97).
RESULTS: During a median follow-up of 52.2 months, the primary outcome occurred in 333 patients (35.3%) in the simvastatin-ezetimibe group and in 355 patients (38.2%) in the placebo group (hazard ratio in the simvastatin-ezetimibe group, 0.96; 95% confidence interval [CI], 0.83 to 1.12; P=0.59).
Fewer patients had ischemic cardiovascular events in the simvastatin-ezetimibe group (148 patients) than in the placebo group (187 patients) (hazard ratio, 0.78; 95% CI, 0.63 to 0.97; P=0.02), mainly because of the smaller number of patients who underwent coronary-artery bypass grafting.
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Where it lands on the map
Rows are treatments, columns are outcomes. The coloured squares are the cells this paper feeds, coloured by the vote it casts there. Click one to jump to what this paper adds to it.
What it adds to each cell
For every cell the paper feeds: the belief in the claim with and without this paper, and this paper's estimate drawn against every other readable study in the cell. The ringed dot is this paper.
Other lipid agents×cardiovascular events
InconclusiveOpen on the map →What to test next →10 readable studies in this cell: 5 favour the treatment, 5 find no difference, 0 favour the comparator.
Statins×cardiovascular events
InconclusiveOpen on the map →What to test next →30 readable studies in this cell: 18 favour the treatment, 11 find no difference, 1 favour the comparator.
Other lipid agents×cardiac & vascular function
InconclusiveOpen on the map →What to test next →4 readable studies in this cell: 0 favour the treatment, 4 find no difference, 0 favour the comparator.
Statins×cardiac & vascular function
InconclusiveOpen on the map →What to test next →11 readable studies in this cell: 4 favour the treatment, 6 find no difference, 1 favour the comparator.
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.
A Multicenter, Double-Blind, Randomized, Placebo-Controlled Study to Evaluate the Effects of Ezetimibe + Simvastatin on Clinical Outcomes in Patients With Aortic Stenosis
Evaluating the Effectiveness of Atorvastatin on the Progression of Aortic Dilatation and Valvular Degeneration in Patients With Bicuspid Aortic Valve (BICATOR)
A Randomized Trial of PCSK9 Inhibitors in Calcific Aortic Valve Stenosis
The Use of ACURATE Neo 2 Valve in Patients With Symptomatic Aortic Valve Stenosis
Clinical Study on the Influence of Calcium and Phosphorus Regulation Therapy on Valvular Heart Disease.
Effect and Safety of PCSK9 Inhibitors on the Progression of Mild/Middle Calcific Aortic Stenosis: A Randomized Controlled Clinical Trial
Who cites it
510 citing papers in PubMed, 10 syntheses or guidelines pooled it, 1,607 citations in OpenAlex.
- Genomic and transcriptomic analyses of aortic stenosis enhance therapeutic target discovery and disease prediction.Nature genetics · 2026Pooled it
- The effects of cholesterol-lowering drugs on neurocognitive function: systematic review and meta analysis.Frontiers in neurology · 2026Pooled it
- Pooled it
- Benefits and Risks of Antihyperlipidemic Medication in Adults with Different Low-Density Lipoprotein Cholesterol Based on the Number Needed to Treat.American journal of cardiovascular drugs : drugs, devices, and other interventions · 2024 · on this mapPooled it
- Is there a shift from cardiovascular to cancer death in lipid-lowering trials? A systematic review and meta-analysis.PloS one · 2024Pooled it
- Effect of ezetimibe-statin combination therapy vs. statin monotherapy on coronary atheroma phenotype and lumen stenosis in patients with coronary artery disease: a meta-analysis and trial sequential analysis.Frontiers in pharmacology · 2024Pooled it
- The Effect of Statins on the Incidence and Prognosis of Bladder Cancer: A Systematic Review and Meta-Analysis.Current oncology (Toronto, Ont.) · 2023Pooled it
- Lipid-Lowering Trials Are Not Representative of Patients Managed in Clinical Practice: A Systematic Review and Meta-Analysis of Exclusion Criteria.Journal of the American Heart Association · 2023Pooled it
- Association Between Lipoprotein(a) and Calcific Aortic Valve Disease: A Systematic Review and Meta-Analysis.Frontiers in cardiovascular medicine · 2022Pooled it
- Update of the Brazilian Guideline for Familial Hypercholesterolemia - 2021.Arquivos brasileiros de cardiologia · 2021Guideline
- Reduction of contrast medium for transcatheter aortic valve replacement planning using a spectral detector CT: a prospective clinical trial.European radiology · 2024Trial
- Prognosis in asymptomatic patients with discordantly graded aortic valve stenosis based on pressure recovery adjusted valve area.Open heart · 2022Trial
- Vitamin K2 and D in Patients With Aortic Valve Calcification: A Randomized Double-Blinded Clinical Trial.Circulation · 2022Trial
- Association of Annual N-Terminal Pro-Brain Natriuretic Peptide Measurements With Clinical Events in Patients With Asymptomatic Nonsevere Aortic Stenosis: A Post Hoc Substudy of the SEAS Trial.JAMA cardiology · 2022Trial
- Low myocardial energetic efficiency is associated with increased mortality in aortic stenosis.Open heart · 2021Trial
- Effect of Denosumab or Alendronic Acid on the Progression of Aortic Stenosis: A Double-Blind Randomized Controlled Trial.Circulation · 2021Trial
- Reduction in Revascularization With Icosapent Ethyl: Insights From REDUCE-IT Revascularization Analyses.Circulation · 2021 · on this mapTrial
- Cardiovascular event rate modifies response to pharmacologic LDL-C lowering in primary prevention: implications of a systematic review and meta-analysis for clinical practice.American journal of preventive cardiology · 2026Article
- Aortic valve stenosis serum IGFBP2 mediates female-specific Evogliptin resistance in valve myofibroblasts.Cell reports · 2026Article
- Complement Component C4B Prioritization Through Drug‒Target Mendelian Randomization and Proteomic Analysis Reveals a Novel Therapeutic Target for Calcific Aortic Valve Stenosis.Cardiovascular drugs and therapy · 2026Article
450 more citing papers are in PubMed but not listed here.
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Authors and funding
17 authors at 14 institutions in 9 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The marked sentences are the ones the graph read a number from.
backgroundHyperlipidemia has been suggested as a risk factor for stenosis of the aortic valve, but lipid-lowering studies have had conflicting results.
methodsWe conducted a randomized, double-blind trial involving 1873 patients with mild-to-moderate, asymptomatic aortic stenosis. The patients received either 40 mg of simvastatin plus 10 mg of ezetimibe or placebo daily. The primary outcome was a composite of major cardiovascular events, including death from cardiovascular causes, aortic-valve replacement, nonfatal myocardial infarction, hospitalization for unstable angina pectoris, heart failure, coronary-artery bypass grafting, percutaneous coronary intervention, and nonhemorrhagic stroke. Secondary outcomes were events related to aortic-valve stenosis and ischemic cardiovascular events.
resultsDuring a median follow-up of 52.2 months, the primary outcome occurred in 333 patients (35.3%) in the simvastatin-ezetimibe group and in 355 patients (38.2%) in the placebo group (hazard ratio in the simvastatin-ezetimibe group, 0.96; 95% confidence interval [CI], 0.83 to 1.12; P=0.59). Aortic-valve replacement was performed in 267 patients (28.3%) in the simvastatin-ezetimibe group and in 278 patients (29.9%) in the placebo group (hazard ratio, 1.00; 95% CI, 0.84 to 1.18; P=0.97). Fewer patients had ischemic cardiovascular events in the simvastatin-ezetimibe group (148 patients) than in the placebo group (187 patients) (hazard ratio, 0.78; 95% CI, 0.63 to 0.97; P=0.02), mainly because of the smaller number of patients who underwent coronary-artery bypass grafting. Cancer occurred more frequently in the simvastatin-ezetimibe group (105 vs. 70, P=0.01).
conclusionsSimvastatin and ezetimibe did not reduce the composite outcome of combined aortic-valve events and ischemic events in patients with aortic stenosis. Such therapy reduced the incidence of ischemic cardiovascular events but not events related to aortic-valve stenosis. (ClinicalTrials.gov number, NCT00092677.)
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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 Socratic graph.