Trial reportCardiovascular drugs and therapy2015

Effect of Metformin on Renal Function After Primary Percutaneous Coronary Intervention in Patients Without Diabetes Presenting with ST-elevation Myocardial Infarction: Data from the GIPS-III Trial.

Rene A Posma, Chris P H Lexis, Erik Lipsic, Maarten W N Nijsten, Kevin Damman, Daan J Touw, Dirk Jan van Veldhuisen, Pim van der Harst, Iwan C C van der Horst

Open access · hybridFull text readRandomized Controlled Trial
In one paragraph

Trial report in Cardiovascular drugs and therapy, 2015. The graph read 4 numbers from its abstract, feeding 4 cells of the map: it finds no clear difference in 1. It also reports an association that does not count as treatment evidence, such as OR 3.30 (1.51 to 7.23) for adverse events & safety. Cited by 14 papers, 4 of them syntheses that pooled it.

4numbers the graph read from it
1cell of the map it votes in
14citing papers in PubMed, 4 pooled it
1.3field-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.

← favours the treatmentfavours the comparator →
0.51 · no effect
Contrast-induced acute kidney injury (CI-AKI)metformin 500 mg twice daily vs placebo twice dailyno clear difference · ckd, t2dfeeds one cell of the map
OR 0.960.52 to 1.75P=0.88
After adjustment for covariates, metformin treatment was not associated with CI-AKI (odds ratio: 0.96, 95%CI 0.52-1.75, P=0.88).

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

Cardiovascular eventsan association or prognostic statement, not a treatment comparison · ckd, t2dfeeds one cell of the map
increase -1.03P = 0.60
OR odds ratio, 95%CI 95 % confidence interval, TIMI thrombolysis in myocardial infarction, eGFR estimated glomerular filtration rate, CK creatine kinase, NT-proBNP N-terminal pro-B-type natriuretic peptide aDefined as Hb <13.7 mg/dl (<8.5 mmol/L) in men and Hb <12.1 mg/dl (<7.5 mmol/L) in women bCalculated using the Chronic Kidney Disease Epidemiology Collaboration study equation cLog transformed dIn total, coumarine derivatives were initiated in 19 (5.0 %) patients during hospitalization on clinical indication eIn total, mineralocorticoid receptor antagonists were initiated in 38 (10.0 %) patients during hospitalization on clinical indication Predictors for contrast-induced acute kidney injury When included in the multivariate analysis, contrast dose was not associated with the development of contrast-induced acute kidney injury (OR: 1.01 per 10 ml increase, 95%CI 0.98-1.03, P = 0.60).
Adverse events & safetyan association or prognostic statement, not a treatment comparison · ckd, t2dfeeds one cell of the map
OR 3.301.51 to 7.23P < 0.01
CI-AKI contrast-induced acute kidney injury, ARB angiotensin-receptor blocker aIn addition to the study medication Multivariate logistic regression analysis identified the initiation of a MRA during hospitalization as the strongest predictor of CI-AKI (odds ratio (OR): 3.30, 95%CI 1.51-7.23, P < 0.01), as presented in Table 3.
Adverse events & safetyan association or prognostic statement, not a treatment comparison · ckd, t2dfeeds one cell of the map
increase -1.03P = 0.60
When included in the multivariate analysis, contrast dose was not associated with the development of CI-AKI (OR: 1.01 per 10 ml increase, 95%CI 0.98-1.03, P = 0.60).Table 3Predictors for contrast-induced acute kidney injuryUnivariateMultivariateCharacteristicOR (95%CI) P-value OR (95%CI) P-value Randomization to metformin1.07 (0.61-1.88)0.820.96 (0.52-1.75)0.88Age (per 5 years increase)1.08 (0.95-1.21)0.241.31 (1.14-1.55)<0.01Female sex1.67 (0.91-3.07)0.10Ischemia time (per 5 mins increase)1.01 (1.00-1.02)<0.01Anemiaa 0.73 (0.34-1.57)0.42Pre-intervention TIMI-flow0.79 (0.62-1.01)0.06Contrast dose (per 5 ml increase)1.02 (1.00-1.05)0.07Length of procedure (per 5 mins increase)1.05 (0.99-1.13)0.13eGFRb (per 5 ml/min/1.72 m2 increase)1.12 (1.01-1.24)0.031.33 (1.14-1.55)<0.01CK (per 10 U/L increase)1.01 (1.00-1.02)<0.01Myocardial band of CK (per 5 U/L increase)1.03 (1.01-1.06)<0.01NT-proBNPc 2.08 (1.28-3.38)<0.011.91 (1.10-3.32)0.02Initiation of a coumarin derivative during hospitalizationd 3.70 (1.39-9.86)<0.01Initiation of a MRA during hospitalizatione 3.60 (1.72-7.57)<0.013.30 (1.51-7.23)<0.01When included in the multivariate analysis, contrast dose was not associated with the devel

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.

Metformin×kidney outcomes

InconclusiveOpen on the map →What to test next →

1 readable study in this cell: 0 favour the treatment, 1 find no difference, 0 favour the comparator.

Belief with this paper
0.25no deciding trial · 0 families support, 0 contradict · against placebo
Without itThis paper is the only evidence family behind the claim. Without it there is no number.
← favours the treatmentfavours the comparator →
1 · no effect
This paper · 2015
OR 0.960.52 to 1.75

Antihypertensives×cardiovascular events

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

1 readable study in this cell: 1 favour the treatment, 0 find no difference, 0 favour the comparator.

Belief with this paper
0.50one trial · 1 family supports, 0 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 0.710.56 to 0.90

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

Antihypertensives×adverse events & safety

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

No other readable study in this cell yet. This paper is the evidence.

Belief with this paperNo claim has been compiled for this cell yet.

Metformin×adverse events & safety

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

22 readable studies in this cell: 9 favour the treatment, 8 find no difference, 5 favour the comparator.

Belief with this paper
0.27contested · 4 families support, 11 contradict · against placebo
Without itNot a counted family in this claim, so removing it changes nothing.
← favours the treatmentfavours the comparator →
0 · no effect
NCT017190031,413 enrolled · 2012
Adjusted mean -0.72-0.95 to -0.48
NCT018093271,186 enrolled · 2013
Δ -0.40-0.59 to -0.21
NCT022730501,136 enrolled · 2014
Δ -8.90-13.3 to -4.50
NCT01126580807 enrolled · 2010
Δ -0.22-0.36 to -0.08
NCT01023581784 enrolled · 2009
Δ -0.67-0.96 to -0.37
NCT00386100688 enrolled · 2006
Δ 1.47-14.8 to 20.8
NCT01217073685 enrolled · 2010
Δ 1.00-9.80 to 13.1
NCT01890122647 enrolled · 2013
Δ -0.68-0.89 to -0.47
NCT00727857600 enrolled · 2007
Δ 0.860.51 to 1.22
NCT01958671461 enrolled · 2013
Δ -2.60-13.1 to 8.10
NCT00328172302 enrolled · 2006
Δ -0.85-1.10 to -0.59
NCT01485614200 enrolled · 2012
Δ 2.40-10.0 to 14.9

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

14 citing papers in PubMed, 4 syntheses or guidelines pooled it, 23 citations in OpenAlex.

  1. Pooled it
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  5. Trial
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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

9 authors at 2 institutions in 1 country.

Rene A Posma
Chris P H Lexis
Erik Lipsic
Maarten W N Nijsten
Kevin Damman
Daan J Touw
Dirk Jan van Veldhuisen
Pim van der Harst
Iwan C C van der Horst
University of Groningen · NLUniversity Medical Center Groningen · NL

Funding

No grant is acknowledged in the PubMed record.

8 · The paper itself

Abstract

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

purposeThe association between metformin use and renal function needs further to be elucidated since data are insufficient whether metformin affects renal function in higher risk populations such as after ST-elevation myocardial infarction (STEMI).

methodsWe studied 379 patients included in the GIPS-III trial in which patients without diabetes or renal dysfunction, who underwent primary percutaneous coronary interventions (PCI) for STEMI, were randomized to metformin 500 mg or placebo twice daily for four months. At baseline and at seven scheduled visits up to four months after PCI, estimated glomerular filtration rate (eGFR) was determined (2582 values). Contrast-induced acute kidney injury (CI-AKI) was defined as an increase in serum creatinine of ≥0.3 mg/dl or 25 % rise within 48 h after PCI.

resultsAt all visits, the mean eGFR was similar in patients randomized to metformin or placebo. Over the four month period, mixed-effect repeated-measures model analysis showed a least-squares mean ± standard error change in eGFR of -5.9±0.8 ml/min/1.73 m2 in the metformin group and −7.1 ±0.8 ml/min/1.73 m2 in the control group (P=0.27 for overall interaction). The incidence of CI-AKI was 14.8 %; 29 (15.2 %) patients in the metformin group versus 27 (14.4 %) controls (P=0.89). After adjustment for covariates, metformin treatment was not associated with CI-AKI (odds ratio: 0.96, 95%CI 0.52−1.75, P=0.88).

conclusionWe conclude that initiation of metformin shortly after primary PCI has no adverse effect on renal function in patients without diabetes or prior renal impairment, further providing evidence of the safety of metformin use after myocardial infarction and subsequent contrast exposure.

Indexed as

Percutaneous Coronary InterventionAcute Kidney InjuryCreatinineDiabetes MellitusFemaleGlomerular Filtration RateHumansHypoglycemic AgentsKidneyMaleMetforminMiddle AgedMyocardial InfarctionCreatinineHypoglycemic AgentsMetformin

Identifiers

PMID27656713
PMCPMC4636992
OpenAlexW1795905593

What Socratic holds

Textfull text, public
LicenceCC BY
Read underepoch 390

Registered trials

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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.