Evidence map›Paper›PMID 26039521›Full record

Trial reportThe New England journal of medicine2015

Ezetimibe Added to Statin Therapy after Acute Coronary Syndromes.

Christopher P Cannon, Michael A Blazing, Robert P Giugliano, Amy McCagg, Jennifer A White, Pierre Theroux, Harald Darius, Basil S Lewis, Ton Oude Ophuis, J Wouter Jukema and 12 more

9 registry-linked trialsOpen access · bronzeAbstract readComparative StudyMulticenter StudyRandomized Controlled Trial
PubMed Publisher
In one paragraph

Trial report in The New England journal of medicine, 2015. 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 1,598 papers, 9 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
1,598citing papers in PubMed, 9 pooled it
451.7field-weighted citation impact, top 1% of its field
1 · What the graph read from 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.

2 · The registry

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.

NCT00202878 phase3completed

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)

Ran2005Enrolled18,144Registered outcomes4Posted comparisons4ConditionsHypercholesterolemia, Myocardial InfarctionArmsezetimibe/simvastatin, Placebo for ezetimibe 10 mg/simvastatin 40 mg combination, Placebo for simvastatin 40 mg, simvastatin
PMID 26330412PMID 25066560PMID 20435175other papers from this trial
Open the trial in the graph
NCT03696940 phase3unknown statusstarted 2018, after this paper: background citation

Estudio clínico Fase III Para Evaluar la Eficacia terapéutica en Pacientes Mexicanos Con Dislipidemia Mediante el Uso vía Oral de L-Carnitina + Atorvastatina Comparado Con Atorvastatina

Ran2018Enrolled120Registered outcomes6Posted comparisons0ConditionsCardiovascular Risk Factor, DyslipidemiasArmsAtorvastatin 10mg, L-Carnitine 500Mg Oral Tablet + Atorvastatin 10 mg
PMID 27046161PMID 25537708PMID 24793440PMID 24793441PMID 24793443PMID 16034009PMID 26939026PMID 17039901PMID 23190071PMID 19604523PMID 25915661PMID 19618992other papers from this trial
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NCT03771053 naunknown statusstarted 2018, after this paper: background citation

Intravascular Ultrasound Evaluation of the Intervention Effect of Simvastatin Combined With Ezetimibe on Coronary Borderline Lesion in Patients With Stable Angina Pectoris and Diabetes Mellitus Compared With Simvastatin Alone

Ran2018Enrolled240Registered outcomes7Posted comparisons0ConditionsCoronary Heart DiseaseArmsEzetimibe with simvastatin, simvastatin
PMID 21446892PMID 19675335PMID 28927191PMID 15389231PMID 16533939PMID 16787216PMID 18940534PMID 20609967PMID 22085316other papers from this trial
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NCT04826354 phase4completedstarted 2021, after this paper: background citation

Effects of High-dose StAtin Versus Low-dose Statin Plus Ezetimibe on Statin-Associated Muscle Symptoms & on Reaching Target LDL-C Levels Among Elderly Patients With Atherosclerotic Cardiovascular Disease

Ran2021Enrolled582Registered outcomes11Posted comparisons0ConditionsAtheroscleroses, CoronaryArmsRosuvastatin, rosuvastatin and ezetimibe
PMID 30423391PMID 28249067PMID 30403574PMID 28007331PMID 28304224PMID 28444290PMID 16453090PMID 22686958PMID 29020411PMID 30580575PMID 21067804PMID 22410123other papers from this trial
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NCT05976893 phase4unknown statusstarted 2023, after this paper: background citation

Study on the Composite Endpoint Event of PCSK9 Inhibitor in Patients With Very High Risk of ASCVD and Cancer

Ran2023Enrolled620Registered outcomes5Posted comparisons0ConditionsASCVD, Atherosclerotic Cardiovascular Disease, Cancer, Proprotein Convertase Subtilisin/Kexin Type 9 InhibitorArmsEvolocumab, Statin
PMID 30403574PMID 25773607PMID 28304224PMID 36031810PMID 35508320PMID 24161333PMID 36017568PMID 37416519PMID 31248666PMID 31887831PMID 29653628PMID 21543628other papers from this trial
Open the trial in the graph
NCT02991118 phase3completednot on this mapstarted 2016, after this paper: background citation

A Long-term, Randomized, Double-blind, Placebo-controlled, Multicenter Study to Evaluate the Efficacy of Bempedoic Acid (ETC-1002) in Patients With Hyperlipidemia at High Cardiovascular Risk Not Adequately Controlled by Their Lipid-Modifying Therapy

TypeinterventionalSponsorEsperion Therapeutics, Inc.Ran2016 to 2018Enrolled779ConditionsHypercholesterolemia, Atherosclerotic Cardiovascular DiseaseArmsbempedoic acid, placebo
NCT03590496 nacompletednot on this mapstarted 2018, after this paper: background citation

Safety and Efficacy of PROPionatE for Reduction of LDL Cholesterol (PROPER-LDL Trial) - A Phase 2 Randomized Placebo Controlled Double-blind Trial

TypeinterventionalSponsorCharite University, Berlin, GermanyRan2018 to 2020Enrolled62ConditionsHypercholesterolemiaArmsCalcium-Propionate 500mg, Placebo
NCT07242599 phase3not yet recruitingnot on this mapstarted 2026, after this paper: background citation

A Multicenter, Randomized, Open-label, Parallel-controlled, Event-driven, Blinded-endpoint Trial Evaluating the Efficacy and Safety of Ongericimab Injection in High-risk Stroke Patients With Intracranial or Extracranial Atherosclerotic Stenosis.

TypeinterventionalSponsorBeijing Tiantan HospitalRan2026 to 2029Enrolled4,810ConditionsIschemic Cerebral InfarctionArmsHigh target group, Low target group
NCT07577518 nanot yet recruitingnot on this mapstarted 2026, after this paper: background citation

Percutaneous Intervention Versus Optimal Medical Therapy in Chronic Coronary Syndrome (PIVOT) Trial

TypeinterventionalSponsorSeoul National University HospitalRan2026 to 2034Enrolled2,301ConditionsChronic Coronary SyndromeArmspercutaneous coronary intervention, Guideline-directed Optimal Medical treatment, Carvedilol Sustained-Release (SR) (Nested RCT subset), Carvedilol Immediate-Release (IR) (Nested RCT subset)
3 · Its place in the literature

Who cites it

1,598 citing papers in PubMed, 9 syntheses or guidelines pooled it, 4,306 citations in OpenAlex.

  1. Pooled it
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  11. Inclisiran in Patients with CKD: Post Hoc Pooled Analysis of Three Phase 3 Trials.Journal of the American Society of Nephrology : JASN · 2026
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  15. PCSK-9-inhibitor therapy improves endothelial function in high-risk patients with cardiovascular disease.Clinical research in cardiology : official journal of the German Cardiac Society · 2026
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1,538 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

22 authors at 9 institutions in 7 countries.

Christopher P CannonFrom the Thrombolysis in Myocardial Infarction (TIMI) Study Group, Brigham and Women's Hospital, and Harvard Medical School, Boston (C.P.C., R.P.G., A.M., K.I., E.A.B., S.D.W., E.B.); Duke Clinical Research Institute (DCRI), Durham, NC (M.A.B., J.A.W., C.R., R.M.C.); Montreal Heart Institute, Montreal (P.T.); Vivantes Neukölln Medical Center, Berlin (H.D.); Lady Davis Carmel Medical Center, Haifa, Israel (B.S.L.); Canisius-Wilhelmina Ziekenhuis, Nijmegen (T.O.O.), and the Netherlands Leiden University Medical Center, Leiden (J.W.J.) - both in the Netherlands; Fondazione IRCCS Policlinico San Matteo and University of Pavia, Pavia, Italy (G.M.D.F.); National Institute of Cardiology, Warsaw, Poland (W.R.); and Merck, Kenilworth, NJ (P.D.L., A.M.T., T.A.M.).
Michael A Blazing
Robert P Giugliano
Amy McCagg
Jennifer A White
Pierre Theroux
Harald Darius
Basil S Lewis
Ton Oude Ophuis
J Wouter Jukema
Gaetano M De Ferrari
Witold Ruzyllo
Paul De Lucca
KyungAh Im
Erin A Bohula
Craig Reist
Stephen D Wiviott
Andrew M Tershakovec
Thomas A Musliner
Eugene Braunwald
Robert M Califf
IMPROVE-IT Investigators
Brigham and Women's Hospital · USMerck & Co., Inc., Rahway, NJ, USA (United States) · USCanisius-Wilhelmina Ziekenhuis · NLCarmel Medical Center · ILInstitute of Cardiology · PLLeiden University Medical Center · NLMontreal Heart Institute · CAUniversity of Pavia · ITVivantes Klinikum · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundStatin therapy reduces low-density lipoprotein (LDL) cholesterol levels and the risk of cardiovascular events, but whether the addition of ezetimibe, a nonstatin drug that reduces intestinal cholesterol absorption, can reduce the rate of cardiovascular events further is not known.

methodsWe conducted a double-blind, randomized trial involving 18,144 patients who had been hospitalized for an acute coronary syndrome within the preceding 10 days and had LDL cholesterol levels of 50 to 100 mg per deciliter (1.3 to 2.6 mmol per liter) if they were receiving lipid-lowering therapy or 50 to 125 mg per deciliter (1.3 to 3.2 mmol per liter) if they were not receiving lipid-lowering therapy. The combination of simvastatin (40 mg) and ezetimibe (10 mg) (simvastatin-ezetimibe) was compared with simvastatin (40 mg) and placebo (simvastatin monotherapy). The primary end point was a composite of cardiovascular death, nonfatal myocardial infarction, unstable angina requiring rehospitalization, coronary revascularization (≥30 days after randomization), or nonfatal stroke. The median follow-up was 6 years.

resultsThe median time-weighted average LDL cholesterol level during the study was 53.7 mg per deciliter (1.4 mmol per liter) in the simvastatin-ezetimibe group, as compared with 69.5 mg per deciliter (1.8 mmol per liter) in the simvastatin-monotherapy group (P<0.001). The Kaplan-Meier event rate for the primary end point at 7 years was 32.7% in the simvastatin-ezetimibe group, as compared with 34.7% in the simvastatin-monotherapy group (absolute risk difference, 2.0 percentage points; hazard ratio, 0.936; 95% confidence interval, 0.89 to 0.99; P=0.016). Rates of prespecified muscle, gallbladder, and hepatic adverse effects and cancer were similar in the two groups.

conclusionsWhen added to statin therapy, ezetimibe resulted in incremental lowering of LDL cholesterol levels and improved cardiovascular outcomes. Moreover, lowering LDL cholesterol to levels below previous targets provided additional benefit. (Funded by Merck; IMPROVE-IT ClinicalTrials.gov number, NCT00202878.).

Indexed as

Acute Coronary SyndromeAgedAnticholesteremic AgentsAzetidinesCardiovascular DiseasesCholesterol, LDLDouble-Blind MethodDrug Therapy, CombinationEzetimibeFemaleHumansHydroxymethylglutaryl-CoA Reductase InhibitorsKaplan-Meier EstimateMaleMiddle AgedSimvastatinAnticholesteremic AgentsAzetidinesCholesterol, LDLEzetimibeHydroxymethylglutaryl-CoA Reductase InhibitorsSimvastatinTriglycerides

Identifiers

PMID26039521
OpenAlexW1520609538

What Socratic holds

Texttitle and abstract
Read underepoch 390

Registered trials

and 3 more above

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.