Trial reportTransplantation2014

More potent lipid-lowering effect by rosuvastatin compared with fluvastatin in everolimus-treated renal transplant recipients.

Ida Robertsen, Anders Asberg, Tone Granseth, Nils Tore Vethe, Fatemeh Akhlaghi, Mwlod Ghareeb, Espen Molden, Morten Reier-Nilsen, Hallvard Holdaas, Karsten Midtvedt

Open access · greenAbstract readClinical TrialComparative Study
In one paragraph

Trial report in Transplantation, 2014. The graph read 1 number from its abstract, feeding 1 cell of the map, but none could be read as for or against, so it casts no vote. Cited by 10 papers, 1 of them a synthesis that pooled it.

1number the graph read from it
0cells of the map it votes in
10citing papers in PubMed, 1 pooled it
1.5field-weighted citation impact, top 19% 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

Lipidscomparator not stated · dyslipidemia, ckdfeeds one cell of the map
decrease -12.2P<0.01
RESULTS: In RTR already receiving fluvastatin, switching to rosuvastatin further decreased LDL cholesterol and total cholesterol by 30.2±12.2% (P<0.01) and 18.2±9.6% (P<0.01), respectively.

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×lipids

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

38 readable studies in this cell: 28 favour the treatment, 4 find no difference, 6 favour the comparator.

Belief with this paper
0.50contested · 21 families support, 7 contradict · against placebo
Without itNot a counted family in this claim, so removing it changes nothing.
← favours the treatmentfavours the comparator →
0 · no effect
NCT002899002,340 enrolled · 2006
Δ -13.2-16.8 to -9.60
reduced -66.0-73.0 to -58.0
NCT02546323543 enrolled · 2015
Δ -35.5-40.2 to -30.7
NCT01678820299 enrolled · 2012
Δ 0.50-4.80 to 5.80
NCT01218204287 enrolled · 2010
Δ 5.47-15.7 to 26.7
NCT0093525931 enrolled · 2009
Δ -51.7
reductions -33.6-38.8 to -28.4

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

10 citing papers in PubMed, 1 synthesis or guideline pooled it, 16 citations in OpenAlex.

  1. Fluvastatin for lowering lipids.The Cochrane database of systematic reviews · 2018
    Pooled it
  2. Use of Statins in Kidney Transplant Recipients in Norway.International journal of environmental research and public health · 2022
    Observational
  3. Article
  4. Article
  5. Article
  6. Article
  7. Article
  8. Article
  9. Review
  10. Review
6 · The record

Corrections and comments

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

7 · Who and what money

Authors and funding

10 authors at 3 institutions in 1 country.

Ida Robertsen1 Department of Pharmaceutical Biosciences, School of Pharmacy, University of Oslo, Oslo, Norway. 2 Department of Transplant Medicine, Oslo University Hospital, Oslo, Norway. 3 Department of Medical Biochemistry, Oslo University Hospital, Oslo, Norway. 4 Department of Pharmacology, Oslo University Hospital, Oslo, Norway. 5 Biomedical and Pharmaceutical Sciences, College of Pharmacy, University of Rhode Island, Kingston, RI. 6 Center of Psychopharmacology, Diakonhjemmet Hospital, Oslo, Norway. 7 Department of Nephrology, Drammen Hospital, Drammen, Norway. 8 Address correspondence to: Ida Robertsen, School of Pharmacy, University of Oslo. P. O. Box 1068 Blindern, 0316 Oslo, Norway.
Anders Asberg
Tone Granseth
Nils Tore Vethe
Fatemeh Akhlaghi
Mwlod Ghareeb
Espen Molden
Morten Reier-Nilsen
Hallvard Holdaas
Karsten Midtvedt
Oslo University Hospital · NODiakonhjemmet Hospital · NOUniversity of Oslo · NO

Funding

NIGMS NIH HHS R15 GM101599NIGMS NIH HHS R15GM101599
8 · The paper itself

Abstract

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

backgroundDyslipidemia is a risk factor for premature cardiovascular morbidity and mortality in renal transplant recipients (RTRs). Pharmacotherapy with mTOR inhibitors aggravates dyslipidemia, thus necessitating lipid-lowering therapy with fluvastatin, pravastatin, or atorvastatin. These agents may not sufficiently lower lipid levels, and therefore, a more potent agent like rosuvastatin maybe needed.

methodsWe have aimed to assess the lipid-lowering effect of rosuvastatin as compared with fluvastatin in RTR receiving everolimus. Safety was assessed as the pharmacokinetic (PK) interaction potential of a rosuvastatin/everolimus combination in RTR. A 12-hour everolimus PK investigation was performed in 12 stable RTR receiving everolimus and fluvastatin (80 mg/d). Patients were then switched to rosuvastatin (20 mg/d), and a follow-up 12/24-hour PK investigation of everolimus/rosuvastatin was performed after 1 month. All other drugs were kept unchanged.

resultsIn RTR already receiving fluvastatin, switching to rosuvastatin further decreased LDL cholesterol and total cholesterol by 30.2±12.2% (P<0.01) and 18.2±9.6% (P<0.01), respectively. Everolimus AUC0-12 was not affected by concomitant rosuvastatin treatment, 80.3±21.3 μg*h/L before and 78.5±21.9 μg*h/L after, respectively (P=0.61). Mean rosuvastatin AUC0-24 was 157±61.7 ng*h/mL, approximately threefold higher than reported in the literature for nontransplants. There were no adverse events, and none of the patients had or developed proteinuria.

conclusionRosuvastatin showed a superior lipid-lowering effect compared to fluvastatin in stable RTR receiving everolimus. The combination of everolimus/rosuvastatin seems to be as safe as the everolimus/fluvastatin combination.

Indexed as

Kidney TransplantationAgedBiomarkersCytochrome P-450 CYP3ADrug InteractionsDrug SubstitutionDyslipidemiasEverolimusFatty Acids, MonounsaturatedFemaleFluorobenzenesFluvastatinGenotypeHumansHydroxymethylglutaryl-CoA Reductase InhibitorsImmunosuppressive AgentsBiomarkersCYP3A5 protein, humanCytochrome P-450 CYP3AEverolimusFatty Acids, MonounsaturatedFluorobenzenesFluvastatinHydroxymethylglutaryl-CoA Reductase InhibitorsImmunosuppressive AgentsIndolesLipidsPyrimidinesRosuvastatin CalciumSirolimusSulfonamides

Identifiers

PMID24521776
PMCPMC4127422
OpenAlexW1975945408

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.