Evidence map›Paper›PMID 26330412›Full record

Trial reportCirculation2015

Achievement of dual low-density lipoprotein cholesterol and high-sensitivity C-reactive protein targets more frequent with the addition of ezetimibe to simvastatin and associated with better outcomes in IMPROVE-IT.

Erin A Bohula, Robert P Giugliano, Christopher P Cannon, Jing Zhou, Sabina A Murphy, Jennifer A White, Andrew M Tershakovec, Michael A Blazing, Eugene Braunwald

Registry-linked trialAbstract readComparative StudyMulticenter StudyRandomized Controlled Trial
PubMed Publisher
In one paragraph

Trial report in Circulation, 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 146 papers, 10 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
146citing papers in PubMed, 10 pooled it
31.6field-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 25066560PMID 26039521PMID 20435175other papers from this trial
Open the trial in the graph
3 · Its place in the literature

Who cites it

146 citing papers in PubMed, 10 syntheses or guidelines pooled it, 329 citations in OpenAlex.

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  8. Guideline
  9. Ezetimibe for the prevention of cardiovascular disease and all-cause mortality events.The Cochrane database of systematic reviews · 2018 · on this map
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  10. Effect of ezetimibe on plasma adipokines: a systematic review and meta-analysis.British journal of clinical pharmacology · 2017 · on this map
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86 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

9 authors at 1 institution in 1 country.

Erin A BohulaFrom TIMI Study Group, Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA (E.A.B., R.P.G., C.P.C., J.Z., S.A.M., E.B.); Duke Clinical Research Institute, Durham, NC (J.W., M.A.B.); and Merck, Kenilworth, NJ (A.M.T.). ebohula@partners.org.
Robert P GiuglianoFrom TIMI Study Group, Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA (E.A.B., R.P.G., C.P.C., J.Z., S.A.M., E.B.); Duke Clinical Research Institute, Durham, NC (J.W., M.A.B.); and Merck, Kenilworth, NJ (A.M.T.).
Christopher P CannonFrom TIMI Study Group, Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA (E.A.B., R.P.G., C.P.C., J.Z., S.A.M., E.B.); Duke Clinical Research Institute, Durham, NC (J.W., M.A.B.); and Merck, Kenilworth, NJ (A.M.T.).
Jing ZhouFrom TIMI Study Group, Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA (E.A.B., R.P.G., C.P.C., J.Z., S.A.M., E.B.); Duke Clinical Research Institute, Durham, NC (J.W., M.A.B.); and Merck, Kenilworth, NJ (A.M.T.).
Sabina A MurphyFrom TIMI Study Group, Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA (E.A.B., R.P.G., C.P.C., J.Z., S.A.M., E.B.); Duke Clinical Research Institute, Durham, NC (J.W., M.A.B.); and Merck, Kenilworth, NJ (A.M.T.).
Jennifer A WhiteFrom TIMI Study Group, Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA (E.A.B., R.P.G., C.P.C., J.Z., S.A.M., E.B.); Duke Clinical Research Institute, Durham, NC (J.W., M.A.B.); and Merck, Kenilworth, NJ (A.M.T.).
Andrew M TershakovecFrom TIMI Study Group, Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA (E.A.B., R.P.G., C.P.C., J.Z., S.A.M., E.B.); Duke Clinical Research Institute, Durham, NC (J.W., M.A.B.); and Merck, Kenilworth, NJ (A.M.T.).
Michael A BlazingFrom TIMI Study Group, Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA (E.A.B., R.P.G., C.P.C., J.Z., S.A.M., E.B.); Duke Clinical Research Institute, Durham, NC (J.W., M.A.B.); and Merck, Kenilworth, NJ (A.M.T.).
Eugene BraunwaldFrom TIMI Study Group, Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA (E.A.B., R.P.G., C.P.C., J.Z., S.A.M., E.B.); Duke Clinical Research Institute, Durham, NC (J.W., M.A.B.); and Merck, Kenilworth, NJ (A.M.T.).
Clinical Research Institute · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundStatins lower low-density lipoprotein cholesterol (LDL-C) and high-sensitivity C-reactive protein (hs-CRP); addition of ezetimibe to statins further reduces LDL-C and hs-CRP. An analysis of the relationship between achieved LDL-C and hs-CRP targets and outcomes for simvastatin and ezetimibe/simvastatin was prespecified in Improved Reduction of Outcomes: Vytorin Efficacy International Trial (IMPROVE-IT). METHODS AND

resultsThe IMPROVE-IT trial randomly assigned 18 144 patients stabilized after acute coronary syndrome to simvastatin or ezetimibe/simvastatin. LDL-C and hs-CRP were measured at baseline and 1 month after randomization. Outcomes were assessed in those achieving one or both of the prespecified targets of LDL-C<70 mg/dL and hs-CRP<2 mg/L versus achieving neither target, adjusting for differences in baseline characteristics. An exploratory analysis examined targets of LDL-C<50 mg/dL and hs-CRP<1 mg/L. Patients meeting both targets at baseline, with no 1-month values, or with end points before 1 month were excluded. Of 15 179 patients, 39% achieved the dual LDL-C (<70 mg/dL) and hs-CRP (<2 mg/L) targets at 1 month, 14% met neither target, 14% met only the hs-CRP target, and 33% met only the LDL-C target. Those achieving dual targets had lower primary end point rates than those meeting neither target (cardiovascular death, major coronary event, or stroke; 38.9% versus 28.0%; adjusted hazard ratio, 0.73; 0.66-0.81; P<0.001). More patients treated with ezetimibe/simvastatin met dual targets than those treated with simvastatin alone (50% versus 29%, P<0.001). The association of dual-target attainment with improved outcomes was similar irrespective of treatment assignment (P-interaction=0.65). Similar findings were observed using the exploratory targets.

conclusionsSignificantly more patients treated with ezetimibe/simvastatin met prespecified and exploratory dual LDL-C and hs-CRP targets than patients treated with simvastatin alone. Reaching both LDL-C and hs-CRP targets was associated with improved outcomes after multivariable adjustment. CLINICAL

trial registrationURL: http://www.clinicaltrials.gov; Unique identifier: NCT00202878.

Indexed as

Acute Coronary SyndromeAgedAnticholesteremic AgentsBiomarkersCardiovascular DiseasesCerebral RevascularizationCholesterol, LDLComorbidityC-Reactive ProteinCreatinineDouble-Blind MethodDrug MonitoringDrug Therapy, CombinationElectrocardiographyEzetimibeFemaleAnticholesteremic AgentsBiomarkersCholesterol, LDLC-Reactive ProteinCreatinineEzetimibeHydroxymethylglutaryl-CoA Reductase InhibitorsSimvastatinacute coronary syndromecholesterol, LDLC-reactive proteinezetimibehydroxymethylglutaryl-CoA reductase inhibitorssecondary prevention

Identifiers

PMID26330412
OpenAlexW2127469535

What Socratic holds

Texttitle and abstract
Read underepoch 390

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.