Metformin in non-Diabetic Patients Presenting with ST Elevation Myocardial Infarction: Rationale and Design of the Glycometabolic Intervention as Adjunct to Primary Percutaneous Intervention in ST Elevation Myocardial Infarction (GIPS)-III Trial

Lexis, Chris P. H.; Horst, Iwan C. C. van der; Lipšic, Erik; Harst, Pim van der; Horst-Schrivers, Anouk N A van der; Wolffenbuttel, Bruce H. R.; Boer, Rudolf A. de; Rossum, Albert C. van; Veldhuisen, Dirk J. van; Smet, Bart J. G. L. de

doi:10.1007/s10557-012-6413-1

Cited by 47 publications

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“…The GIPS-III trial was a single center, randomized, double blind, placebo-controlled study. The study design, baseline characteristics and primary outcomes have previously been reported [31,32]. In short, patients presenting with STEMI to the University Medical Center Groningen between January 1, 2011, and May 26, 2013 who underwent successful PCI with implantation of at least 1 stent with a diameter of at least 3 mm were eligible for inclusion in the trial.…”

Section: Methodsmentioning

confidence: 99%

The Effect of Metformin on Diastolic Function in Patients Presenting with ST-Elevation Myocardial Infarction

et al. 2016

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IntroductionDiastolic dysfunction is an important predictor of poor outcome after myocardial infarction. Metformin treatment improved diastolic function in animal models and patients with diabetes. Whether metformin improves diastolic function in patients presenting with ST-segment elevation myocardial infarction (STEMI) is unknown.MethodsThe GIPS-III trial randomized STEMI patients, without known diabetes, to metformin or placebo initiated directly after PCI. The previously reported primary endpoint was left ventricular ejection fraction at 4 months, which was unaffected by metformin treatment. This is a predefined substudy to determine an effect of metformin on diastolic function. For this substudy trans-thoracic echocardiography was performed during hospitalization and after 4 months. Diastolic dysfunction was defined as having the combination of a functional alteration (i.e. decreased tissue velocity: mean of septal e’ and lateral e’) and a structural alteration (i.e. increased left atrial volume index (LAVI)). In addition, left ventricular mass index and transmitral flow velocity (E) to mean e' ratio (E/e’) were measured to determine an effect of metformin on individual echocardiographic markers of diastolic function.ResultsIn 237 (63%) patients included in the GIPS-III trial diastolic function was measured during hospitalization as well as at 4 months. Diastolic dysfunction was present in 11 (9%) of patients on metformin and 11 (9%) patients on placebo treatment (P = 0.98) during hospitalization. After 4 months 22 (19%) of patients with metformin and 18 (15%) patients with placebo (P = 0.47) had diastolic dysfunction. In addition, metformin did not improve any of the individual echocardiographic markers of diastolic function.ConclusionsIn contrast to experimental and observational data, our randomized placebo controlled trial did not suggest a beneficial effect of short-term metformin treatment on diastolic function in STEMI patients.

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Section: Methodsmentioning

confidence: 99%

The Effect of Metformin on Diastolic Function in Patients Presenting with ST-Elevation Myocardial Infarction

et al. 2016

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“…This study was performed as a substudy of the glycometabolic intervention as adjunct to primary percutaneous intervention in ST elevation myocardial infarction (GIPS)-III trial (clinicaltrials.gov NTC01217307) [12–14]. The GIPS-III trial was a prospective, single center, double blind, randomized clinical trial that compared metformin 500 mg twice daily to placebo treatment in 380 non-diabetic patients requiring primary PCI for STEMI.…”

Section: Methodsmentioning

confidence: 99%

Chronic ischemic mitral regurgitation and papillary muscle infarction detected by late gadolinium-enhanced cardiac magnetic resonance imaging in patients with ST-segment elevation myocardial infarction

et al. 2016

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BackgroundBoth papillary muscle infarction (PMI) and chronic ischemic mitral regurgitation (CIMR) are associated with reduced survival after myocardial infarction. The influence of PMI on CIMR and factors influencing both entities are incompletely understood.ObjectivesWe sought to determine the influence of PMI on CIMR after primary percutaneous coronary intervention (PCI) for ST-segment elevation myocardial infarction (STEMI) and to define independent predictors of PMI and CIMR.MethodsBetween January 2011 and May 2013, 263 patients (mean age 57.8 ± 11.5 years) underwent late gadolinium-enhanced cardiac magnetic resonance imaging and transthoracic echocardiography 4 months after PCI for STEMI. Infarct size, PMI, and mitral valve and left ventricular geometric and functional parameters were assessed. Univariate and multivariate analyses were performed to identify predictors of PMI and CIMR (≥grade 2+).ResultsPMI was present in 61 patients (23 %) and CIMR was present in 86 patients (33 %). In patients with PMI, 52 % had CIMR, and in patients without PMI, 27 % had CIMR (P < 0.001). In multivariate analyses, infarct size [odds ratio (OR) 1.09 (95 % confidence interval 1.04–1.13), P < 0.001], inferior MI [OR 4.64 (1.04–20.62), P = 0.044], and circumflex infarct-related artery [OR 8.21 (3.80–17.74), P < 0.001] were independent predictors of PMI. Age [OR 1.08 (1.04–1.11), P < 0.001], infarct size [OR 1.09 (1.03-1.16), P = 0.003], tethering height [OR 19.30 (3.28–113.61), P = 0.001], and interpapillary muscle distance [OR 3.32 (1.31–8.42), P = 0.011] were independent predictors of CIMR.ConclusionsThe risk of PMI is mainly associated with inferior infarction and infarction in the circumflex coronary artery. Although the prevalence of CIMR is almost doubled in the presence of PMI, PMI is not an independent predictor of CIMR. Tethering height and interpapillary muscle distance are the strongest independent predictors of CIMR.

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“…Currently, several clinical trials are being performed to test this hypothesis. As an example, the Glycometabolic Intervention as adjunct to Primary percutaneous intervention in ST elevation myocardial infarction (GIPS)-III trial is a prospective, single center, double blind, randomized, placebo-controlled trial, which is currently studying the efficacy of metformin with the aim to preserve left ventricular ejection fraction in non-diabetic patients presenting with ST elevation MI (STEMI) [35].…”

Section: Metformin In Patients Following Acute Coronary Syndromementioning

confidence: 99%

Metformin revisited: A critical review of the benefit–risk balance in at-risk patients with type 2 diabetes

Scheen

Paquot

2013

Diabetes & Metabolism

148

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Metformin is unanimously considered as the first-line glucose-lowering agent. Theoretically, however, it cannot be prescribed in a large proportion of patients with type 2 diabetes because of the presence of numerous contraindications corresponding to situations that may increase the risk of lactic acidosis. Various observational data from real life showed that many diabetic patients considered as "at risk" still receive metformin, often without appropriate dose adjustment, apparently without any harm, especially no increased risk of lactic acidosis. More interestingly, recent data suggest that type 2 diabetes patients who are considered as being "at risk" because of the presence of traditional contraindications still take benefit from metformin therapy, with a reduction of morbidity and mortality compared with other glucose-lowering agents, more particularly sulfonylureas. The present review analyzes the benefit-risk balance of metformin therapy in special populations, namely patients with stable coronary artery disease, acute coronary syndrome or myocardial infarction, congestive heart failure, renal impairment or chronic kidney disease, hepatic dysfunction and chronic respiratory insufficiency, all conditions that may theoretically increase the risk of lactic acidosis. A special attention will be devoted to elderly patients with type 2 diabetes. Indeed, this population is growing rapidly and older patients may cumulate several comorbidities

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Metformin in non-Diabetic Patients Presenting with ST Elevation Myocardial Infarction: Rationale and Design of the Glycometabolic Intervention as Adjunct to Primary Percutaneous Intervention in ST Elevation Myocardial Infarction (GIPS)-III Trial

Cited by 47 publications

References 45 publications

The Effect of Metformin on Diastolic Function in Patients Presenting with ST-Elevation Myocardial Infarction

The Effect of Metformin on Diastolic Function in Patients Presenting with ST-Elevation Myocardial Infarction

Chronic ischemic mitral regurgitation and papillary muscle infarction detected by late gadolinium-enhanced cardiac magnetic resonance imaging in patients with ST-segment elevation myocardial infarction

Metformin revisited: A critical review of the benefit–risk balance in at-risk patients with type 2 diabetes

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