Document Detail

Effect of metformin on left ventricular function after acute myocardial infarction in patients without diabetes: the GIPS-III randomized clinical trial.
MedLine Citation:
PMID:  24687169     Owner:  NLM     Status:  MEDLINE    
IMPORTANCE: Metformin treatment is associated with improved outcome after myocardial infarction in patients with diabetes. In animal experimental studies metformin preserves left ventricular function.
OBJECTIVE: To evaluate the effect of metformin treatment on preservation of left ventricular function in patients without diabetes presenting with ST-segment elevation myocardial infarction (STEMI).
DESIGN, SETTING, AND PARTICIPANTS: Double-blind, placebo-controlled study conducted among 380 patients who underwent primary percutaneous coronary intervention (PCI) for STEMI at the University Medical Center Groningen, The Netherlands, between January 1, 2011, and May 26, 2013.
INTERVENTIONS: Metformin hydrochloride (500 mg) (n = 191) or placebo (n = 189) twice daily for 4 months.
MAIN OUTCOMES AND MEASURES: The primary efficacy measure was left ventricular ejection fraction (LVEF) after 4 months, assessed by magnetic resonance imaging. A secondary efficacy measure was the N-terminal pro-brain natriuretic peptide (NT-proBNP) concentration after 4 months. The incidence of major adverse cardiac events (MACE; the combined end point of death, reinfarction, or target-lesion revascularization) was recorded until 4 months as a secondary efficacy measure.
RESULTS: At 4 months, all patients were alive and none were lost to follow-up. LVEF was 53.1% (95% CI, 51.6%-54.6%) in the metformin group (n = 135), compared with 54.8% (95% CI, 53.5%-56.1%) (P = .10) in the placebo group (n = 136). NT-proBNP concentration was 167 ng/L in the metformin group (interquartile range [IQR], 65-393 ng/L) and 167 ng/L in the placebo group (IQR, 74-383 ng/L) (P = .66). MACE were observed in 6 patients (3.1%) in the metformin group and in 2 patients (1.1%) in the placebo group (P = .16). Creatinine concentration (79 µmol/L [IQR, 70-87 µmol/L] vs 79 µmol/L [IQR, 72-89 µmol/L], P = .61) and glycated hemoglobin (5.9% [IQR, 5.6%-6.1%] vs 5.9% [IQR, 5.7%-6.1%], P = .15) were not significantly different between both groups. No cases of lactic acidosis were observed.
CONCLUSIONS AND RELEVANCE: Among patients without diabetes presenting with STEMI and undergoing primary PCI, the use of metformin compared with placebo did not result in improved LVEF after 4 months. The present findings do not support the use of metformin in this setting.
TRIAL REGISTRATION: Identifier: NCT01217307.
Chris P H Lexis; Iwan C C van der Horst; Erik Lipsic; Wouter G Wieringa; Rudolf A de Boer; Ad F M van den Heuvel; Hindrik W van der Werf; Remco A J Schurer; Gabija Pundziute; Eng S Tan; Wybe Nieuwland; Hendrik M Willemsen; Bernard Dorhout; Barbara H W Molmans; Anouk N A van der Horst-Schrivers; Bruce H R Wolffenbuttel; Gert J ter Horst; Albert C van Rossum; Jan G P Tijssen; Hans L Hillege; Bart J G L de Smet; Pim van der Harst; Dirk J van Veldhuisen;
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Publication Detail:
Type:  Journal Article; Randomized Controlled Trial; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  JAMA     Volume:  311     ISSN:  1538-3598     ISO Abbreviation:  JAMA     Publication Date:  2014 Apr 
Date Detail:
Created Date:  2014-04-16     Completed Date:  2014-04-28     Revised Date:  2014-09-17    
Medline Journal Info:
Nlm Unique ID:  7501160     Medline TA:  JAMA     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1526-35     Citation Subset:  AIM; IM    
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MeSH Terms
Double-Blind Method
Hypoglycemic Agents / therapeutic use*
Magnetic Resonance Imaging
Metformin / therapeutic use*
Middle Aged
Myocardial Infarction / complications,  drug therapy*,  physiopathology
Percutaneous Coronary Intervention
Treatment Outcome
Ventricular Dysfunction, Left / prevention & control*
Ventricular Function, Left / drug effects*
Reg. No./Substance:
0/Hypoglycemic Agents; 9100L32L2N/Metformin
Iwan C C van der Horst / ; Chris P H Lexis / ; Erik Lipsic / ; Pim van der Harst / ; Dirk J van Veldhuisen / ; Wouter G Wieringa / ; Rudolf A de Boer / ; Ad F M van den Heuvel / ; Hindrik W van der Werf / ; Remco A J Schurer / ; Gabija Pundziute / ; Eng S Tan / ; Hendrik M Willemsen / ; Anouk N A van der Horst-Schrivers / ; Bruce H R Wolffenbuttel / ; Bernard Dorhout / ; Hans L Hillege / ; Wybe Nieuwland / ; Peter van der Meer / ; René A Tio / ; Jenifer Coster / ; Yoran M Hummel / ; Barbara H W Molmans / ; Gert J ter Horst / ; Remco Renken / ; Anita J Sibeijn-Kuiper / ; Bart J G L de Smet / ; Albert C van Rossum / ; Robin Nijveldt / ; Jan G P Tijssen / ; Iwan C C van der Horst / ; Erik Lipsic / ; Pim van der Harst / ; Rudolf A de Boer / ; Anouk N A van der Horst-Schrivers / ; Bruce H R Wolffenbuttel / ; Dirk J van Veldhuisen / ; Chris P H Lexis / ; Iwan C C van der Horst / ; Erik Lipsic / ; Pim van der Harst / ; Dirk J van Veldhuisen / ; Jan G P Tijssen / ; Robert J de Winter / ; Arne J Risselada / ; Richard M de Jong / ; Rob K Gonera / ; Vincent M Roolvink / ; André P van Beek / ; Fred van den Berg /
Comment In:
Nat Rev Cardiol. 2014 Jun;11(6):314   [PMID:  24736756 ]

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