Evidence map›Paper›PMID 30630361›Full record

Trial reportCirculation. Cardiovascular quality and outcomes2019

Medication Discontinuation in the IMPROVE-IT Trial.

Ann Marie Navar, Matthew T Roe, Jennifer A White, Christopher P Cannon, Yuliya Lokhnygina, L Kristin Newby, Robert P Giugliano, Andrew M Tershakovec, Eugene Braunwald, Robert M Califf and 1 more

Registry-linked trialOpen access · greenAbstract readComparative StudyMulticenter StudyRandomized Controlled Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Circulation. Cardiovascular quality and outcomes, 2019. 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 19 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
19citing papers in PubMed, 3 pooled it
10.4field-weighted citation impact, top 2% 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 26039521PMID 20435175other papers from this trial
Open the trial in the graph
3 · Its place in the literature

Who cites it

19 citing papers in PubMed, 3 syntheses or guidelines pooled it, 50 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Pooled it
  4. Article
  5. Article
  6. Lipid-Lowering Therapy after Acute Coronary Syndrome.Journal of clinical medicine · 2024
    Review
  7. Lipid-lowering approaches to manage statin-intolerant patients.European heart journal supplements : journal of the European Society of Cardiology · 2024
    Article
  8. Article
  9. Review
  10. Review
  11. Article
  12. Understanding Study Drug Discontinuation Through EUCLID.Frontiers in cardiovascular medicine · 2022
    Article
  13. Article
  14. Article
  15. Optimal Medical Therapy Prescription in Patients with Acute Coronary Syndrome in the Netherlands: A Multicenter Pilot Registry.American journal of cardiovascular drugs : drugs, devices, and other interventions · 2021
    Article
  16. Article
  17. Article
  18. Review
  19. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

11 authors at 3 institutions in 1 country.

Ann Marie NavarDuke Clinical Research Institute, Duke University School of Medicine, Durham, NC (A.M.N., M.T.R., J.A.W., Y.L., L.K.N., M.A.B.).
Matthew T RoeDuke Clinical Research Institute, Duke University School of Medicine, Durham, NC (A.M.N., M.T.R., J.A.W., Y.L., L.K.N., M.A.B.).
Jennifer A WhiteDuke Clinical Research Institute, Duke University School of Medicine, Durham, NC (A.M.N., M.T.R., J.A.W., Y.L., L.K.N., M.A.B.).
Christopher P CannonTIMI Study Group, Division of Cardiovascular Medicine, Brigham and Women's Hospital, Boston, MA (C.P.C., R.P.G., E.B.).
Yuliya LokhnyginaDuke Clinical Research Institute, Duke University School of Medicine, Durham, NC (A.M.N., M.T.R., J.A.W., Y.L., L.K.N., M.A.B.).
L Kristin NewbyDuke Clinical Research Institute, Duke University School of Medicine, Durham, NC (A.M.N., M.T.R., J.A.W., Y.L., L.K.N., M.A.B.).
Robert P GiuglianoDuke Clinical Research Institute, Duke University School of Medicine, Durham, NC (A.M.N., M.T.R., J.A.W., Y.L., L.K.N., M.A.B.).
Andrew M TershakovecMerck & Co, Inc, Rahway, NJ (A.M.T.).
Eugene BraunwaldTIMI Study Group, Division of Cardiovascular Medicine, Brigham and Women's Hospital, Boston, MA (C.P.C., R.P.G., E.B.).
Robert M CaliffDuke Forge, Duke University, Durham, NC (A.M.N., R.M.C.).
Michael A BlazingDuke Clinical Research Institute, Duke University School of Medicine, Durham, NC (A.M.N., M.T.R., J.A.W., Y.L., L.K.N., M.A.B.).
Duke University · USBrigham and Women's Hospital · USMerck & Co., Inc., Rahway, NJ, USA (United States) · US

Funding

Preventing Cardiovascular Disease through Improved Risk Prediction and CommunicationK01HL133416 · NHLBI · DUKE UNIVERSITY · PI NAVAR, ANN MARIE · 2016 to 2020
$707k
NHLBI NIH HHS K01 HL133416
6 · The paper itself

Abstract

backgroundAlthough cholesterol-lowering medications can reduce the risk of recurrent cardiovascular events, premature discontinuation limits effectiveness. Discontinuation rates have not been systematically reported for lipid-lowering trials. METHODS AND

resultsWe evaluated medication discontinuation in IMPROVE-IT (Improved Reduction of Outcomes: Vytorin Efficacy International Trial), which evaluated placebo+simvastatin versus ezetimibe+simvastatin in patients hospitalized with the acute coronary syndrome and followed longitudinally postdischarge. Reasons for discontinuation were evaluated from randomization through study end (median 71.9 [interquartile range 51.8-85.8] months). Kaplan-Meier (KM) discontinuation rates were evaluated at 30 days, 1 year, and through year 7, and compared by treatment arm and region, with Cox proportional hazards modeling used to evaluate predictors of discontinuation. Overall, 46.7% of subjects discontinued study medication (KM rate by study end 50.9% [95% CI, 50.1%-51.7%]). The risk of discontinuation was highest early in the trial but decreased with increasing time, with a terminal KM rate per 100 person-years of 8.4 (8.2-8.6) from years 1 to 7. Discontinuation was higher in the placebo+simvastatin versus ezetimibe+simvastatin arm (KM rate 52.0% versus 49.8%, P=0.049) and was highest in the United States (7-year KM rate 57.4%). In multivariable modeling, smoking, prior revascularization, hypertension, unstable angina, female sex, nonwhite race, and US location were associated with higher discontinuation rates.

conclusionsAlthough discontinuation was highest early and stabilized to 8% per year, because of prolonged follow-up, most discontinuation occurred after year 1. Adding ezetimibe to statin therapy did not increase discontinuation risk. Geographic differences and patient-level factors should be considered in trial design and analysis. CLINICAL

trial registrationURL: https://www.clinicaltrials.gov . Unique identifier: NCT00202878.

Indexed as

Acute Coronary SyndromeAgedAsiaAustraliaBiomarkersDouble-Blind MethodDrug Administration ScheduleDrug UtilizationDyslipidemiasEuropeEzetimibe, Simvastatin Drug CombinationFemaleHumansHydroxymethylglutaryl-CoA Reductase InhibitorsLipidsMaleBiomarkersEzetimibe, Simvastatin Drug CombinationHydroxymethylglutaryl-CoA Reductase InhibitorsLipidsacute coronary syndromecholesterolezetimibemedication adherencestatin

Identifiers

PMID30630361
PMCPMC6541480
OpenAlexW2910401579

What OpenQuestion holds

Texttitle and abstract
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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 OpenQuestion graph.