Evidence map›Paper›PMID 38573708›Full record

Trial reportClinical cancer research : an official journal of the American Association for Cancer Research2024

Statins Do Not Significantly Affect Oxidative Nitrosative Stress Biomarkers in the PREVENT Randomized Clinical Trial.

Igor Makhlin, Biniyam G Demissei, Ralph D'Agostino, W Greg Hundley, Camelia Baleanu-Gogonea, Nicholas S Wilcox, Anna Chen, Amanda M Smith, Nathaniel Sean O'Connell, James L Januzzi and 5 more

Registry-linked trialOpen access · bronzeAbstract readRandomized Controlled Trial
In one paragraph

Trial report in Clinical cancer research : an official journal of the American Association for Cancer Research, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT01988571 (Preventing Anthracycline Cardiovascular Toxicity With Statins), which is not on this map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
2.4field-weighted citation impact, top 11% 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.

NCT01988571 phase2completednot on this map

Preventing Anthracycline Cardiovascular Toxicity With Statins (PREVENT)

TypeinterventionalSponsorWake Forest University Health SciencesRan2014 to 2020Enrolled279ConditionsBreast Cancer, LymphomaArmsAtorvastatin, Placebo
3 · Its place in the literature

Who cites it

6 citing papers in PubMed, 6 citations in OpenAlex.

  1. Article
  2. Review
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  5. Review
  6. 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

15 authors at 7 institutions in 2 countries.

Igor Makhlin *Division of Hematology and Oncology, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.ORCID 0000-0001-7374-7330
Biniyam G Demissei *Division of Cardiology, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.ORCID 0000-0003-0875-4985
Ralph D'AgostinoDepartment of Biostatistics and Data Science, Wake Forest School of Medicine, Winston-Salem, North Carolina.ORCID 0000-0002-3550-8395
W Greg HundleyDivision of Cardiology, Pauley Heart Center, Virginia Commonwealth University, Richmond, Virginia.ORCID 0000-0002-2433-8853
Camelia Baleanu-GogoneaDepartment of Cardiovascular and Metabolic Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio.ORCID 0000-0003-4147-5347
Nicholas S WilcoxDivision of Cardiology, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.ORCID 0000-0002-3693-7650
Anna ChenPerelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.ORCID 0000-0001-5667-7174
Amanda M SmithDivision of Cardiology, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.ORCID 0000-0002-9881-236X
Nathaniel Sean O'ConnellDepartment of Biostatistics and Data Science, Wake Forest School of Medicine, Winston-Salem, North Carolina.ORCID 0000-0002-3827-5152
James L JanuzziMassachusetts General Hospital and Baim Institute for Clinical Research, Boston, Massachusetts.ORCID 0000-0002-8338-1798
Glenn J LesserDepartment of Medicine, Hematology and Oncology, Wake Forest School of Medicine, Winston-Salem, North Carolina.ORCID 0009-0003-5471-8907
Marielle Scherrer-CrosbieDivision of Cardiology, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.ORCID 0000-0001-6375-9266
Borja IbáñezCentro Nacional de Investigaciones Cardiovasculares (CNIC), CIBER-CV, Madrid, Spain.ORCID 0000-0002-5036-254X
W H Wilson TangDepartment of Cardiovascular and Metabolic Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio.ORCID 0000-0002-8335-735X
Bonnie KyDivision of Cardiology, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.ORCID 0000-0002-6628-9981
University of Pennsylvania · USWake Forest University · USBaim Institute for Clinical Research · USCleveland Clinic · USCleveland Clinic Lerner College of Medicine · USSpanish National Centre for Cardiovascular Research · ESVirginia Commonwealth University · US

Funding

ECOG-ACRIN NCORP Research Base - TMISTUG1CA189828 · NCI · ECOG-ACRIN MEDICAL RESEARCH FOUNDATION · PI Peter J ODwyer, MITCHELL D. SCHNALL · 2014 to 2026
$199.7M
Collaborations and NCORP Collective ManagementUG1CA189823 · NCI · MAYO CLINIC ROCHESTER · PI Evanthia Galanis, Olwen Hahn · 2014 to 2026
$120.6M
Wake Forest NCORP Research BaseUG1CA189824 · NCI · WAKE FOREST UNIVERSITY HEALTH SCIENCES · PI Emily Van Meter Dressler, GLENN J LESSER · 2014 to 2026
$57.9M
Comprehensive Cancer Center of Wake Forest University CCOP Research BaseU10CA081851 · NCI · WAKE FOREST UNIVERSITY HEALTH SCIENCES · PI SHAW, EDWARD G · 1999 to 2013
$22.0M
Preventing Anthracycline Cardiovascular Toxicity with StatinsR01HL118740 · NHLBI · WAKE FOREST UNIVERSITY HEALTH SCIENCES · PI HUNDLEY, WILLIAM GREGORY · 2013 to 2018
$4.2M
Multimarker Risk Prediction in Cancer Therapy CardiotoxicityR01HL118018 · NHLBI · UNIVERSITY OF PENNSYLVANIA · PI KY, BONNIE · 2014 to 2018
$3.7M
MENTORING IN PATIENT-ORIENTED RESEARCH IN DEEP PHENOTYPING IN CARDIO-ONCOLOGYK24HL167127 · NHLBI · UNIVERSITY OF PENNSYLVANIA · PI Bonnie Ky · 2023 to 2026
$496k
Markers of Oxidative and Nitrosative Stress in Anthracycline Cardiotoxicity and Statin CardioprotectionR21HL141802 · NHLBI · UNIVERSITY OF PENNSYLVANIA · PI KY, BONNIE · 2018 to 2019
$469k
National Cancer Institute (NCI) U10CA081851National Cancer Institute (NCI) UG1CA189823National Cancer Institute (NCI) UG1CA189824National Cancer Institute (NCI) UG1CA189828National Heart, Lung, and Blood Institute (NHLBI) R01HL118018National Heart, Lung, and Blood Institute (NHLBI) R01HL118740National Heart, Lung, and Blood Institute (NHLBI) R21HL14802NCI NIH HHS U10 CA081851NCI NIH HHS UG1 CA189823NCI NIH HHS UG1 CA189824NCI NIH HHS UG1 CA189828NHLBI NIH HHS K24 HL167127NHLBI NIH HHS R01 HL118018NHLBI NIH HHS R01 HL118740NHLBI NIH HHS R21 HL141802
6 · The paper itself

Abstract

purposePreventing Anthracycline Cardiovascular Toxicity with Statins (PREVENT; NCT01988571) randomized patients with breast cancer or lymphoma receiving anthracyclines to atorvastatin 40 mg daily or placebo. We evaluated the effects of atorvastatin on oxidative and nitrosative stress biomarkers, and explored whether these biomarkers could explain the lack of effect of atorvastatin on LVEF (left ventricular ejection fraction) in PREVENT. PATIENTS AND

methodsBlood samples were collected and cardiac MRI was performed before doxorubicin initiation and at 6 and 24 months. Thirteen biomarkers [arginine-nitric oxide metabolites, paraoxonase-1 (PON-1) activity, and myeloperoxidase] were measured. Dimensionality reduction using principal component analysis was used to define biomarker clusters. Linear mixed-effects models determined the changes in biomarkers over time according to treatment group. Mediation analysis determined whether biomarker clusters explained the lack of effect of atorvastatin on LVEF.

resultsAmong 202 participants with available biomarkers, median age was 53 years; 86.6% had breast cancer; median LVEF was 62%. Cluster 1 levels, reflecting arginine methylation metabolites, were lower over time with atorvastatin, although this was not statistically significant (P = 0.081); Cluster 2 levels, reflecting PON-1 activity, were significantly lower with atorvastatin (P = 0.024). There were no significant changes in other biomarker clusters (P > 0.05). Biomarker clusters did not mediate an effect of atorvastatin on LVEF (P > 0.05).

conclusionsAtorvastatin demonstrated very modest effects on oxidative/nitrosative stress biomarkers in this low cardiovascular risk population. Our findings provide potential mechanistic insight into the lack of effect of atorvastatin on LVEF in the PREVENT trial.

Indexed as

AtorvastatinBiomarkersBreast NeoplasmsHydroxymethylglutaryl-CoA Reductase InhibitorsNitrosative StressOxidative StressAdultAgedArginineAryldialkylphosphataseDoxorubicinFemaleHumansMaleMiddle AgedArginineAryldialkylphosphataseAtorvastatinBiomarkersDoxorubicinHydroxymethylglutaryl-CoA Reductase Inhibitors

Identifiers

PMID38573708
PMCPMC11287023
OpenAlexW4393951042

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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.