Observational studyAmerican heart journal2021

Statins and atherosclerotic cardiovascular outcomes in patients on incident dialysis and with atherosclerotic heart disease.

Jay S Shavadia, Jonathan Wilson, Daniel Edmonston, Alyssa Platt, Patti Ephraim, Rasheeda Hall, Benjamin A Goldstein, L Ebony Boulware, Eric Peterson, Jane Pendergast and 1 more

Erratum issuedOpen access · greenAbstract readObservational Study
In one paragraph

Observational study in American heart journal, 2021. The graph read 6 numbers from its abstract, feeding 2 cells of the map, but none could be read as for or against, so it casts no vote. It also reports 2 associations that do not count as treatment evidence, such as HR 0.96 (0.94 to 0.98) for all-cause mortality. An erratum has been issued. Cited by 11 papers, 1 of them a synthesis that pooled it.

6numbers the graph read from it
0cells of the map it votes in
11citing papers in PubMed, 1 pooled it
1.8field-weighted citation impact, top 14% 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.

Read, but not usablea number the graph found but could not read as for or against

Composite risk of all-cause mortality, nonfatal myocardial infarction, or stroke thereafterstatin use vs statin nonusean association or prognostic statement, not a treatment comparison · ascvd, ckdfeeds one cell of the map
HR 0.980.96 to 1.01
Statin use was modestly associated with lower all-cause mortality (HR 0.96, 95% CI 0.94-0.98; E value = 1.21) and, similarly, a modest lower composite risk of all-cause mortality, nonfatal myocardial infarction, or stroke over the first 2 years (HR 0.90, 95% CI 0.88-0.91) but attenuated thereafter (HR 0.98, 95% CI 0.96-1.01).
Fatal/nonfatal myocardial infarction or strokestatin use vs statin nonusean association or prognostic statement, not a treatment comparison · ascvd, ckdfeeds one cell of the map
HR 1.000.97 to 1.02
Over a median 662 days, statin users had similar risk of fatal/nonfatal myocardial infarction or stroke overall (hazard ratio [HR] 1.00, 95% CI 0.97-1.02), or in subgroups (age< 50 years [HR = 1.05, 95% CI 0.95-1.17]; waitlisted for kidney transplant [HR 0.99, 95% CI 0.97-1.02]).
Fatal/nonfatal myocardial infarction or strokestatin use vs statin nonuse, in age< 50 yearsan association or prognostic statement, not a treatment comparison · ascvd, ckdfeeds one cell of the map
HR 1.050.95 to 1.17
Over a median 662 days, statin users had similar risk of fatal/nonfatal myocardial infarction or stroke overall (hazard ratio [HR] 1.00, 95% CI 0.97-1.02), or in subgroups (age< 50 years [HR = 1.05, 95% CI 0.95-1.17]; waitlisted for kidney transplant [HR 0.99, 95% CI 0.97-1.02]).
Fatal/nonfatal myocardial infarction or strokestatin use vs statin nonuse, in waitlisted for kidney transplantan association or prognostic statement, not a treatment comparison · ascvd, ckdfeeds one cell of the map
HR 0.990.97 to 1.02
Over a median 662 days, statin users had similar risk of fatal/nonfatal myocardial infarction or stroke overall (hazard ratio [HR] 1.00, 95% CI 0.97-1.02), or in subgroups (age< 50 years [HR = 1.05, 95% CI 0.95-1.17]; waitlisted for kidney transplant [HR 0.99, 95% CI 0.97-1.02]).
All-cause mortalitystatin use vs statin nonusean association or prognostic statement, not a treatment comparison · ascvd, ckdfeeds one cell of the map
HR 0.960.94 to 0.98
Statin use was modestly associated with lower all-cause mortality (HR 0.96, 95% CI 0.94-0.98; E value = 1.21) and, similarly, a modest lower composite risk of all-cause mortality, nonfatal myocardial infarction, or stroke over the first 2 years (HR 0.90, 95% CI 0.88-0.91) but attenuated thereafter (HR 0.98, 95% CI 0.96-1.01).
Composite risk of all-cause mortality, nonfatal myocardial infarction, or stroke over the first 2 yearsstatin use vs statin nonusean association or prognostic statement, not a treatment comparison · ascvd, ckdfeeds one cell of the map
HR 0.900.88 to 0.91
Statin use was modestly associated with lower all-cause mortality (HR 0.96, 95% CI 0.94-0.98; E value = 1.21) and, similarly, a modest lower composite risk of all-cause mortality, nonfatal myocardial infarction, or stroke over the first 2 years (HR 0.90, 95% CI 0.88-0.91) but attenuated thereafter (HR 0.98, 95% CI 0.96-1.01).

clause the extractor read what became the number

2 · Its place on the map

Where it lands on the map

Rows are treatments, columns are outcomes. The coloured squares are the cells this paper feeds, coloured by the vote it casts there. Click one to jump to what this paper adds to it.

supports the treatmentfavours the comparatorno clear differenceread, but no usable result
3 · What it changes

What it adds to each cell

For every cell the paper feeds: the belief in the claim with and without this paper, and this paper's estimate drawn against every other readable study in the cell. The ringed dot is this paper.

Statins×cardiovascular events

No readable resultOpen on the map →What to test next →

29 readable studies in this cell: 19 favour the treatment, 9 find no difference, 1 favour the comparator.

Belief with this paper
0.86replicated · 12 families support, 2 contradict · against placebo
Without itNot a counted family in this claim, so removing it changes nothing.
← favours the treatmentfavours the comparator →
1 · no effect
HR 0.750.64 to 0.88
NCT023442907,769 enrolled · 2015
HR 0.640.48 to 0.84
HR 0.880.69 to 1.11
NCT03944512102 enrolled · 2019
RR 0.670.37 to 1.19

This paper's own estimate is on a different scale from the rest of the cell, so it is not drawn here.

Statins×all-cause mortality

No readable resultOpen on the map →What to test next →

13 readable studies in this cell: 3 favour the treatment, 8 find no difference, 2 favour the comparator.

Belief with this paper
0.50contested · 3 families support, 2 contradict · against placebo
Without itNot a counted family in this claim, so removing it changes nothing.
← favours the treatmentfavours the comparator →
1 · no effect
NCT023442907,769 enrolled · 2015
HR 0.880.70 to 1.12
HR 1.000.90 to 1.12
NCT03944512102 enrolled · 2019
RR 0.670.37 to 1.19
RR 0.990.89 to 1.11

This paper's own estimate is on a different scale from the rest of the cell, so it is not drawn here.

4 · 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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

5 · Its place in the literature

Who cites it

11 citing papers in PubMed, 1 synthesis or guideline pooled it, 17 citations in OpenAlex.

  1. Pooled it
  2. Endothelial dysfunction in chronic kidney disease: a clinical perspective.American journal of physiology. Heart and circulatory physiology · 2025
    Review
  3. Review
  4. Article
  5. Peritoneal Dialysis Aggravates and Accelerates Atherosclerosis in UremicJournal of the American Heart Association · 2024
    Article
  6. Article
  7. Article
  8. Article
  9. Review
  10. Review
  11. Article
6 · The record

Corrections and comments

7 · Who and what money

Authors and funding

11 authors at 4 institutions in 2 countries.

Jay S ShavadiaDepartment of Medicine, Division of Cardiology, University of Saskatchewan, Saskatoon, Saskatchewan, Canada; Duke Clinical Research Institute, Durham, NC. Electronic address: jss372@usask.ca.
Jonathan WilsonDepartment of Biostatistics and Bioinformatics, Duke University School of Medicine, Durham, NC.
Daniel EdmonstonDuke Clinical Research Institute, Durham, NC; Department of Medicine, Duke University School of Medicine, Durham, NC.
Alyssa PlattDuke Clinical Research Institute, Durham, NC; Department of Biostatistics and Bioinformatics, Duke University School of Medicine, Durham, NC.
Patti EphraimDepartment of Epidemiology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD.
Rasheeda HallDuke Clinical Research Institute, Durham, NC; Department of Medicine, Duke University School of Medicine, Durham, NC.
Benjamin A GoldsteinDuke Clinical Research Institute, Durham, NC; Department of Biostatistics and Bioinformatics, Duke University School of Medicine, Durham, NC.
L Ebony BoulwareDuke Clinical Research Institute, Durham, NC; Department of Medicine, Duke University School of Medicine, Durham, NC.
Eric PetersonDuke Clinical Research Institute, Durham, NC; Department of Medicine, Duke University School of Medicine, Durham, NC.
Jane PendergastDuke Clinical Research Institute, Durham, NC; Department of Biostatistics and Bioinformatics, Duke University School of Medicine, Durham, NC.
Julia J SciallaDuke Clinical Research Institute, Durham, NC; Department of Medicine, Duke University School of Medicine, Durham, NC; Departments of Medicine and Public Health Sciences, University of Virginia School of Medicine, Charlottesville, VA.
Duke University · USClinical Research Institute · USJohns Hopkins University · USUniversity of Virginia · US

Funding

Support for QA/QC for Prior Approval ProcessUL1TR002553 · NCATS · DUKE UNIVERSITY · PI LI, JENNIFER S, MCNAMARA, JAMES O. · 2018 to 2023
$58.5M
Integrated Mineral Metabolism Treatment Strategies in Patients on DialysisR01DK111952 · NIDDK · UNIVERSITY OF VIRGINIA · PI SCIALLA, JULIA J · 2017 to 2020
$1.6M
Deprescribing for Older Dialysis PatientsK76AG059930 · NIA · DUKE UNIVERSITY · PI HALL, RASHEEDA K · 2018 to 2022
$1.2M
NCATS NIH HHS UL1 TR002553NIDDK NIH HHS R01 DK111952
8 · The paper itself

Abstract

The marked sentences are the ones the graph read a number from.

Statins failed to reduce cardiovascular (CV) events in trials of patients on dialysis. However, trial populations used criteria that often excluded those with atherosclerotic heart disease (ASHD), in whom statins have the greatest benefit, and included outcome composites with high rates of nonatherosclerotic CV events that may not be modified by statins. Here, we study whether statin use associates with lower atherosclerotic CV risk among patients with known ASHD on dialysis, including in those likely to receive a kidney transplant, a group excluded within trials but with lower competing mortality risks.

methodsUsing data from the United States Renal Data System including Medicare claims, we identified adults initiating dialysis with ASHD. We matched statin users 1:1 to statin nonusers with propensity scores incorporating hard matches for age and kidney transplant listing status. Using Cox models, we evaluated associations of statin use with the primary composite of fatal/nonfatal myocardial infarction and stroke (including within prespecified subgroups of younger age [<50 years] and waitlisting status); secondary outcomes included all-cause mortality and the composite of all-cause mortality, nonfatal myocardial infarction, or stroke.

resultsOf 197,716 patients with ASHD, 47,562 (24%) were consistent statin users from which we created 46,186 matched pairs. Over a median 662 days, statin users had similar risk of fatal/nonfatal myocardial infarction or stroke overall (hazard ratio [HR] 1.00, 95% CI 0.97-1.02), or in subgroups (age< 50 years [HR = 1.05, 95% CI 0.95-1.17]; waitlisted for kidney transplant [HR 0.99, 95% CI 0.97-1.02]). Statin use was modestly associated with lower all-cause mortality (HR 0.96, 95% CI 0.94-0.98; E value = 1.21) and, similarly, a modest lower composite risk of all-cause mortality, nonfatal myocardial infarction, or stroke over the first 2 years (HR 0.90, 95% CI 0.88-0.91) but attenuated thereafter (HR 0.98, 95% CI 0.96-1.01).

conclusionsOur large observational analyses are consistent with trials in more selected populations and suggest that statins may not meaningfully reduce atherosclerotic CV events even among incident dialysis patients with established ASHD and those likely to receive kidney transplants.

Indexed as

Renal DialysisAdultAgedAged, 80 and overAge FactorsAtherosclerosisCause of DeathCoronary DiseaseFemaleHumansHydroxymethylglutaryl-CoA Reductase InhibitorsKaplan-Meier EstimateKidney Failure, ChronicKidney TransplantationMaleMiddle AgedHydroxymethylglutaryl-CoA Reductase Inhibitors

Identifiers

PMID33096103
PMCPMC9011977
OpenAlexW3093531331

What Socratic holds

Texttitle and abstract
LicenceTDM
Read underepoch 390

Registered trials

None linked

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.