ArticleThe New England journal of medicine2008
Analyses of cancer data from three ezetimibe trials.
Article in The New England journal of medicine, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It reports registered trial NCT00202878. Cited by 66 papers, 7 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.
A Multicenter, Double-Blind, Randomized Study to Establish the Clinical Benefit and Safety of Vytorin (Ezetimibe/Simvastatin Tablet) vs Simvastatin Monotherapy in High-Risk Subjects Presenting With Acute Coronary Syndrome (IMProved Reduction of Outcomes: Vytorin Efficacy International Trial - IMPROVE IT)
Open the trial in the graphA Multicenter, Double-Blind, Randomized, Placebo-Controlled Study to Evaluate the Effects of Ezetimibe + Simvastatin on Clinical Outcomes in Patients With Aortic Stenosis
Study of Heart and Renal Protection (SHARP): The Effects of Lowering LDL-cholesterol With Simvastatin 20mg Plus Ezetimibe 10mg in Patients With Chronic Kidney Disease: a Randomized Placebo-controlled Trial
Who cites it
66 citing papers in PubMed, 7 syntheses or guidelines pooled it, 230 citations in OpenAlex.
- The Relationship between Statin Intake and Risk of Pancreatic Cancer: A Systematic Review and Meta-analysis.Current drug research reviews · 2025Pooled it
- Statins and the risk of pancreatic cancer: A systematic review and meta-analysis of 2,797,186 patients.Cardiology journal · 2024Pooled it
- HMG CoA reductase inhibitors (statins) for people with chronic kidney disease not requiring dialysis.The Cochrane database of systematic reviews · 2023Pooled it
- Pooled it
- Clinical efficacy and safety of Ezetimibe on major cardiovascular endpoints: systematic review and meta-analysis of randomized controlled trials.PloS one · 2015 · on this mapPooled it
- Potential increased risk of cancer from commonly used medications: an umbrella review of meta-analyses.Annals of oncology : official journal of the European Society for Medical Oncology · 2014Pooled it
- Effects of folic acid supplementation on overall and site-specific cancer incidence during the randomised trials: meta-analyses of data on 50,000 individuals.Lancet (London, England) · 2013Pooled it
- The Effect of Atorvastatin on Breast Cancer Biomarkers in High-Risk Women.Cancer prevention research (Philadelphia, Pa.) · 2016Trial
- Ascertainment, classification, and impact of neoplasm detection during prolonged treatment with dual antiplatelet therapy with prasugrel vs. clopidogrel following acute coronary syndrome.European heart journal · 2016Trial
- The effects of lowering LDL cholesterol with simvastatin plus ezetimibe in patients with chronic kidney disease (Study of Heart and Renal Protection): a randomised placebo-controlled trial.Lancet (London, England) · 2011 · on this mapTrial
- Intensive lowering of LDL cholesterol with 80 mg versus 20 mg simvastatin daily in 12,064 survivors of myocardial infarction: a double-blind randomised trial.Lancet (London, England) · 2010Trial
- Fluvastatin reduces proliferation and increases apoptosis in women with high grade breast cancer.Breast cancer research and treatment · 2010Trial
- Real-world evidence on the additional cancer risk reduction of ezetimibe: a 10-year nationwide retrospective cohort study emulating a target trial.Journal of cancer research and clinical oncology · 2025Article
- Total-, LDL-, and HDL-cholesterol, apolipoproteins, and triglycerides with risk of total and fatal prostate cancer in Black and White men in the ARIC study.The Prostate · 2023Article
- Global incidence, mortality, and burden of esophageal cancer, and its correlation with SDI, metabolic risks, fasting plasma glucose, LDL cholesterol, and body mass index: An ecological study.Health science reports · 2023Article
- Promotion of colorectal cancer cell death by ezetimibeFrontiers in pharmacology · 2023Article
- Ezetimibe and Cancer: Is There a Connection?Frontiers in pharmacology · 2022Review
- The safety and efficacy of Ezetimibe Plus Statins on ASVD and Related Diseases.Aging and disease · 2021Article
- Emerging Non-statin Treatment Options for Lowering Low-Density Lipoprotein Cholesterol.Frontiers in cardiovascular medicine · 2021Review
- Prospective Evaluation of Malignancy in 17,708 Patients Randomized to Ezetimibe Versus Placebo: Analysis From IMPROVE-IT.JACC. CardioOncology · 2020Article
6 more citing papers are in PubMed but not listed here.
Corrections and comments
- Commented on by
- Commented on by
- Commented on by
- Commented on by
- Comment on
Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
Abstract
backgroundFive years of statin therapy lowers low-density lipoprotein (LDL) cholesterol substantially and, over a 5-year period, results in reductions in the incidence of cardiovascular events. The Simvastatin and Ezetimibe in Aortic Stenosis (SEAS) trial (ClinicalTrials.gov number, NCT00092677) has raised the hypothesis that adding ezetimibe to statin therapy for larger LDL cholesterol reductions might increase the incidence of cancer.
methodsWe compared the results of a hypothesis-generating analysis of the incidence of cancer in the SEAS trial of ezetimibe plus simvastatin in 1873 patients (mean follow-up after ezetimibe or matching placebo was begun, 4.1 years) with a hypothesis-testing analysis of cancer data from the two large ongoing trials of this regimen: the Study of Heart and Renal Protection (SHARP) (NCT00125593) with 9264 patients (mean follow-up, 2.7 years) and the Improved Reduction of Outcomes: Vytorin Efficacy International Trial (IMPROVE-IT) (NCT00202878), currently with 11,353 patients (mean follow-up, 1.0 year).
resultsIn the SEAS trial, assignment to ezetimibe was associated with an increase in any new onset of cancer (101 patients in the active-treatment group vs. 65 in the control group) from several cancer sites. In SHARP and IMPROVE-IT combined, there was no overall excess of cancer (313 active-treatment vs. 326 control; risk ratio, 0.96; 95% confidence interval, 0.82 to 1.12; P=0.61) and no significant excess at any particular site. Among patients assigned to ezetimibe, there were more, albeit not significantly more, deaths from cancer (97, vs. 72 in the control group; P=0.07), but there were also fewer, although not significantly fewer, other cases of cancer (216, vs. 254 in the control group; P=0.08). There was no evidence of a trend in the risk ratio for incidence of or death from cancer with increasing duration of follow-up.
conclusionsThe available results from these three trials do not provide credible evidence of any adverse effect of ezetimibe on rates of cancer. Follow-up of longer duration will permit the balance of risks and benefits to be determined more reliably.
Indexed as
Identifiers
What Socratic holds
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.