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Randomized Controlled Trial
. 2016 Dec 15;11(12):e0168340.
doi: 10.1371/journal.pone.0168340. eCollection 2016.

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

Lawien Al Ali  1 , Minke T Hartman  1 , Chris P H Lexis  1 , Yoran M Hummel  1 , Erik Lipsic  1 , Joost P van Melle  1 , Dirk J van Veldhuisen  1 , Adriaan A Voors  1 , Iwan C C van der Horst  2 , Pim van der Harst  1
Affiliations
Randomized Controlled Trial

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

Lawien Al Ali et al. PLoS One. .

Abstract

Introduction: Diastolic 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.

Methods: The 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.

Results: In 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.

Conclusions: In 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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Conflict of interest statement

The authors have declared that no competing interests exist.

Figures

Fig 1
Fig 1. Flowchart of echocardiographic assessment during hospitalization and at 4 months according to randomization.
STEMI denotes ST-segment elevation myocardial infarction.
Fig 2
Fig 2. Barchart of classification of diastolic function during hospitalization and at 4 months according to randomization.
Fig 3
Fig 3. Barchart of prevalence of abnormal individual parameters of diastolic function during hospitalization and at 4 months according to randomization.
See this image and copyright information in PMC

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