SynthesisPloS one2015
Clinical efficacy and safety of Ezetimibe on major cardiovascular endpoints: systematic review and meta-analysis of randomized controlled trials.
Synthesis in PloS one, 2015. The graph read 5 numbers from its abstract, feeding 3 cells of the map: it finds no clear difference in 3. It is linked to trial NCT04862962 (Retrospective Study to Evaluate the Safety of the Fixed-dose Combination Rosuvastatin / Ezetimibe as a Treatment for Patients With Dyslipidaemia in Usual Medical Practice.), which is not on this map. Cited by 19 papers, 4 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 E+simvastatin combination also increased the risk for all outcomes (all-cause death RR 2.52, 95% CI 0.65-9.74; CV deaths 3.04, 0.48-19.21; not-CV deaths 3.03, 0.12-73.5; MI 1.91, 0.42-8.70; stroke 2.38, 0.46-12.35; SAEs 1.45, 0.95-2.23).
In SHARP and SEAS E+simvastatin did not reduce all-cause death (RR respectively 1.02, 95% CI 0.94-1.11; and 1.04, 0.79-1.36), though at the same time there was a tendency towards reduction of the risk of CV death (RR 0.93, 95% CI 0.80-1.07; and 0.83, 0.56-1.22 respectively) and towards an increase of the risk on non-CV death (RR 1.09, 95% CI) 0.98-1.21; and 1.26, 0.85-1.86 respectively).
All-cause deaths were 105 in the E group, and 100 in the placebo group (HR 1.04; 95% CI 0.79-1.36).
The meta-analysis of the two trials showed a null effect of E+simvastatin for allcause death (RR 1.02, 95% CI 0.95-1.09) and SAEs (RR 1.01, 95% CI 0.96-1.06); a trend toward advantage for MI (RR 0.81, 95% CI 0.66-1.00), stroke (RR 0.86, 95% CI 0.72-1.00) and CV deaths (RR o.91, 95% CI 0.80-1-04) and a trend toward damage for non-CV death (RR 1.08, 95% CI 0.99-1.18) and for cancer (RR 1.18, 95% CI 0.80-1.74).
Examples include torcetrapib plus atorvastatin vs. atorvastatin [30] (CV outcome HR 1.25; 95% CI 1.14-2.19; all-cause death 1.58; 95% CI 1.14-2.19); dalcetrapib plus statin vs. statin [31] (CV outcome HR 1.04; 95% CI 0.93-1.16); niacin plus simvastatin vs. simvastatin [32] (CV outcome HR 1.02; 95% CI 0.87-1.2; all-cause death 1.16; 95% CI 0.87-1.56).
clause the extractor read what became the number
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.
Statins×all-cause mortality
InconclusiveOpen on the map →What to test next →13 readable studies in this cell: 3 favour the treatment, 8 find no difference, 2 favour the comparator.
This paper's own estimate is on a different scale from the rest of the cell, so it is not drawn here.
Other lipid agents×all-cause mortality
InconclusiveOpen on the map →What to test next →2 readable studies in this cell: 1 favour the treatment, 1 find no difference, 0 favour the comparator.
This paper's own estimate is on a different scale from the rest of the cell, so it is not drawn here.
Statins×cardiovascular events
InconclusiveOpen on the map →What to test next →29 readable studies in this cell: 17 favour the treatment, 11 find no difference, 1 favour the comparator.
This paper's own estimate is on a different scale from the rest of the cell, so it is not drawn here.
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.
Retrospective Study to Evaluate the Safety of the Fixed-dose Combination Rosuvastatin / Ezetimibe as a Treatment for Patients With Dyslipidaemia in Usual Medical Practice.
Who cites it
19 citing papers in PubMed, 4 syntheses or guidelines pooled it, 37 citations in OpenAlex.
- National Heart Center/Saudi Heart Association 2025 Guidelines for Cardiovascular Diseases Prevention and Risk Assessment.Saudi medical journal · 2026Guideline
- Lipid-Lowering Efficacy of Ezetimibe in Patients with Atherosclerotic Cardiovascular Disease: A Systematic Review and Meta-Analyses.American journal of cardiovascular drugs : drugs, devices, and other interventions · 2020Pooled it
- Ezetimibe for the prevention of cardiovascular disease and all-cause mortality events.The Cochrane database of systematic reviews · 2018 · on this mapPooled it
- Effect of ezetimibe on plasma adipokines: a systematic review and meta-analysis.British journal of clinical pharmacology · 2017 · on this mapPooled it
- Effects of ezetimibe and anticoagulant combined therapy on progressing stroke: a randomized, placebo-controlled study.Journal of neurology · 2016Trial
- Strategies for the Secondary Prevention of Atherosclerotic Cardiovascular Disease.US cardiology · 2025Review
- Statin Use in Children and Adolescents - Dos, Don'ts and Practical Tips.Current atherosclerosis reports · 2024Review
- Ezetimibe: Integrating Established Use with New Evidence - A Comprehensive Review.Current atherosclerosis reports · 2024Review
- Efficacy and Safety of Bempedoic Acid in Patients with High Cardiovascular Risk: An Update.Current vascular pharmacology · 2024Review
- Anti-Hypercholesterolemia Effects of Edible Seaweed Extracts and Metabolomic Changes in Hep-G2 and Caco-2 Cell Lines.Life (Basel, Switzerland) · 2023Article
- Review
- Article
- Real-World Evidence Evaluation on the Lipid Profile, Therapeutic Goals, and Safety of the Fixed-Dose Combination of Rosuvastatin/Ezetimibe (Trezete®) in Dyslipidemia Patients.Cardiology research and practice · 2022Article
- Safety of ezetimibe in lipid-lowering treatment: systematic review and meta-analysis of randomised controlled trials and cohort studies.BMJ medicine · 2022Article
- Cholesterol-Lowering Treatment in Chronic Kidney Disease: Multistage Pairwise and Network Meta-Analyses.Scientific reports · 2019Article
- Comparison of the Effects of Ezetimibe-Statin Combination Therapy on Major Adverse Cardiovascular Events in Patients with and without Diabetes: A Meta-Analysis.Endocrinology and metabolism (Seoul, Korea) · 2018Article
- Effect of Ezetimibe Monotherapy on Low-Density Lipoprotein Cholesterol and on Markers of Cholesterol Synthesis and Absorption in Japanese Patients With Hypercholesterolemia.Journal of clinical medicine research · 2017Article
- High-density Lipoprotein and Low-density Lipoprotein Therapeutic Approaches in Acute Coronary Syndromes.Current cardiology reviews · 2017Review
- Tanshinone IIA Modulates Low Density Lipoprotein Uptake via Down-Regulation of PCSK9 Gene Expression in HepG2 Cells.PloS one · 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
5 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The marked sentences are the ones the graph read a number from.
backgroundRandomized clinical trials (RCTs) about Ezetimibe's efficacy on patient-oriented outcomes have given discordant results. The aim of this study was to determine the net effect of Ezetimibe and of the widely marketed combination, Ezetimibe+simvastatin, on mortality and morbidity outcomes. METHODS AND
findingsWe searched for RCT on Ezetimibe using MEDLINE, CCTR, EMBASE, ClinicalTrials.gov databases up to December 2013, Merck and Novartis online registers, and personal communications. Two authors independently selected trials fulfilling these criteria: RCTs comparing Ezetimibe±statin or another lipid-lowering drug against placebo, or against the same lipid-lowering drug at the same dosage, with a follow-up at least 24 weeks and one or more of these outcomes: all-cause mortality, cardiovascular (CV) mortality, stroke, myocardial infarction (MI), cancer, serious adverse events (SAEs); we assessed the risk of bias using the Cochrane checklist. We extracted the data for major clinical events as a dichotomous measure, with the patient the unit of analysis. Pooled analysis was done with random and fixed effect based models. Trials comparing Ezetimibe plus a lipid-lowering drug against the same lipidlowering drug representing the net effect of Ezetimibe, showed a nonsignificant tendency toward damage for cancer, MI, stroke and SAEs. Ezetimibe+simvastatin vs. simvastatin alone showed a stronger tendency towards a higher risk for all-cause death (2.52; 0.65-9.74), CV death (3.04; 0.48-19.21), non-CV death (3.03; 0.12-73.50), MI (1.91; 0.42-8.70), stroke (2.38; 0.46-12.35), cancer (RR 11.11; 0.62-198.29), and SAEs (1.45; 0.95-2.23). Limitations include small numbers of events and inadequate power of the pooling. Trials comparing Ezetimibe+simvastatin vs placebo showed non-significant effects: MI (0.81; 0.66-1.00 p = 0.051), all-cause death (1.02; 0.95-1.09), CV death (0.91; 0.80-1.04), non-CV death (108; 0.99-1.18), stroke (0.86; 0.72-1.04), cancer (1.18; 0.80-1.74), SAEs (1.01; 0.96-1.06).
conclusionsEzetimibe±simvastatin had inconsistent effects on important outcomes. No firm conclusions are possible, but findings indicative of damage suggest much more selective use of Ezetimibe±simvastatin.
Indexed as
Identifiers
What OpenQuestion 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 OpenQuestion graph.