Evidence map›Paper›PMID 34396246›Full record

ArticleJACC. CardioOncology2020

Prospective Evaluation of Malignancy in 17,708 Patients Randomized to Ezetimibe Versus Placebo: Analysis From IMPROVE-IT.

Robert P Giugliano, Baris Gencer, Stephen D Wiviott, Jeong-Gun Park, Charles S Fuchs, Wolfram Goessling, Thomas A Musliner, Andrew M Tershakovec, Michael A Blazing, Robert Califf and 2 more

Registry-linked trialOpen access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in JACC. CardioOncology, 2020. 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 8 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed, 1 pooled it
1.6field-weighted citation impact, top 16% 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

8 citing papers in PubMed, 1 synthesis or guideline pooled it, 11 citations in OpenAlex.

  1. Pooled it
  2. Review
  3. Review
  4. Article
  5. Review
  6. Ezetimibe and Cancer: Is There a Connection?Frontiers in pharmacology · 2022
    Review
  7. Dyslipidemia in breast cancer patients increases the risk of SAR-CoV-2 infection.Infection, genetics and evolution : journal of molecular epidemiology and evolutionary genetics in infectious diseases · 2021
    Review
  8. 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

12 authors at 6 institutions in 1 country.

Robert P GiuglianoTIMI Study Group, Division of Cardiovascular Medicine, Brigham and Women's Hospital, and Department of Medicine, Harvard Medical School, Boston, Massachusetts, USA.
Baris GencerTIMI Study Group, Division of Cardiovascular Medicine, Brigham and Women's Hospital, and Department of Medicine, Harvard Medical School, Boston, Massachusetts, USA.
Stephen D WiviottTIMI Study Group, Division of Cardiovascular Medicine, Brigham and Women's Hospital, and Department of Medicine, Harvard Medical School, Boston, Massachusetts, USA.
Jeong-Gun ParkTIMI Study Group, Division of Cardiovascular Medicine, Brigham and Women's Hospital, and Department of Medicine, Harvard Medical School, Boston, Massachusetts, USA.
Charles S FuchsSmilow Cancer Hospital at Yale New Haven, New Haven, Connecticut, USA.
Wolfram GoesslingDivision of Gastroenterology, Massachusetts General Hospital, Boston, Massachusetts, USA.
Thomas A MuslinerMerck, Kenilworth, New Jersey, USA.
Andrew M TershakovecMerck, Kenilworth, New Jersey, USA.
Michael A BlazingDuke Clinical Research Institute, Durham, North Carolina, USA.
Robert CaliffVerily Life Sciences and Google Health, South San Francisco, California, USA.
Christopher P CannonTIMI Study Group, Division of Cardiovascular Medicine, Brigham and Women's Hospital, and Department of Medicine, Harvard Medical School, Boston, Massachusetts, USA.
Eugene BraunwaldTIMI Study Group, Division of Cardiovascular Medicine, Brigham and Women's Hospital, and Department of Medicine, Harvard Medical School, Boston, Massachusetts, USA.
Brigham and Women's Hospital · USMerck & Co., Inc., Rahway, NJ, USA (United States) · USClinical Research Institute · USGoogle (United States) · USMassachusetts General Hospital · USSmilow Cancer Hospital · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundAn increased risk of malignancy was reported with simvastatin/ezetimibe in 1,873 patients in the SEAS (Simvastatin and Ezetimibe in Aortic Stenosis) trial.

objectivesThe purpose of this study was to clarify this unexpected finding in a larger sample size of patients stabilized after acute coronary syndrome, we conducted a prospective systematic analysis of malignancy events in IMPROVE-IT (Improved Reduction of Outcomes: Vytorin Efficacy International Trial).

methodsWithin IMPROVE-IT, 17,708 patients post-acute coronary syndrome were randomized to either ezetimibe 10 mg or matching placebo on a background of simvastatin 40 mg who took ≥1 dose of the study drug. Suspected tumors (benign and malignant) reported by investigators or identified from a review of adverse events were adjudicated by oncologists without knowledge of drug assignment. The primary malignancy endpoint included new, relapsing, or progressive malignancies (excluding nonmelanotic skin malignancies). The secondary endpoint was death due to malignancy.

resultsIn this trial, 1,470 patients developed the primary malignancy endpoint during a median 6 years of follow-up. The most common malignancy locations were prostate (18.9%), lung (16.8%), and bladder (8.8%) with no differences by treatment group (p > 0.05 for each location). Kaplan-Meier 7-year rates of malignancies were similar with ezetimibe and placebo (10.2% vs. 10.3%; hazard ratio: 1.03; 95% confidence interval: 0.93 to 1.14; p = 0.56), as were the rates for malignancy death (3.8% vs. 3.6%; hazard ratio: 1.04; 95% confidence interval: 0.88 to 1.23; p = 0.68).

conclusionsAmong 17,708 patients receiving simvastatin 40 mg daily, those randomized to ezetimibe 10 mg daily had a similar incidence of malignancy and deaths due to malignancy compared with those receiving placebo during a median follow-up of 6 years (96,377 patient-years). (IMPROVE-IT: Examining Outcomes in Subjects With Acute Coronary Syndrome: Vytorin [Ezetimibe/Simvastatin] vs Simvastatin [P04103]; NCT00202878).

Indexed as

ACS, acute coronary syndromeacute coronary syndromesBMI, body mass indexcancerCI, confidence intervalezetimibeHR, hazard ratiohs-CRP, high-sensitive C-reactive proteinKM, Kaplan-MeierLDL-C, low-density lipoprotein cholesterollipid-lowering therapylipidsmalignancyPCSK9, proprotein convertase subtilisin kexin 9PH, proportional hazardRR, risk ratiostatin

Identifiers

PMID34396246
PMCPMC8352126
OpenAlexW3084764100

What Socratic holds

Textmetadata
LicenceCC BY-NC-ND
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.