This study is planned to investigate the impact of Empagliflozin on biomarkers of heart failure in patients with myocardial infarction with and without type 2 diabetes mellitus within 6 months after the event.
Type 2 diabetes mellitus (T2DM) is associated with an about two to three-fold increased risk for cardiovascular events as compared to subjects without diabetes. Sodium-dependent glucose cotransporter 2 (SGLT-2) is mainly expressed in human kidneys and small intestinal cells. In the proximal tubule of the nephron SGLT-2 is responsible for the reabsorption of approximately 90% of the filtrated glucose. Inhibition of SGLT-2 was shown to increase renal glucose excretion and to lower glucose. Subsequently, a number of SGLT-2 inhibitors were developed and are currently approved for the treatment of type 2 diabetes. Recently, Zinman et al published the results of the Cardiovascular Outcome Event Trial in Type 2 Diabetes Mellitus Patient trial (EMPA REG OUTCOME TRIAL) where the cardiovascular impact of a glucose lowering regimen including Empagliflozin as compared to usual glucose control without an SGLT-2 inhibitor was investigated. The trial demonstrated an unexpected reduction in the primary composite endpoint, comprising cardiovascular death, non-fatal myocardial infarction and non-fatal stroke. The reduction was mainly driven by a 38% relative risk reduction in cardiovascular deaths; moreover they demonstrated an impressive 35% relative risk reduction in the secondary endpoint hospitalization for heart failure. Of note, the beneficial effects observed in the Empagliflozin group seem to occur very rapidly after commencing the treatment, as suggested by the early separation of the Kaplan-Meier curves. However, the mechanisms responsible for this finding remain unclear. Diuretic effects with subsequent impact on hemodynamics or potential cardioprotective effects of glucagon, which levels rise under the treatment with SGLT-2 inhibitors and the resulting rise in ketone bodies or a small increase in hematocrit have been suggested. The aim of our trial is to investigate whether Empagliflozin treatment commenced within 72-h after acute myocardial infarction has an impact on heart failure in subjects with and without diabetes mellitus type 2.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
476
The subject will receive Empagliflozin 10 mg orally once daily for 26 weeks.
The subject will receive Placebo orally once daily for 26 weeks.
Barmherzige Brüder Eisenstadt
Eisenstadt, Burgenland, Austria
Klinikum Klagenfurt am Wörthersee
Klagenfurt, Carinthia, Austria
Universitätsklinikum St. Pölten
Sankt Pölten, Lower Austria, Austria
Changes of Nt-proBNP (N-terminales Pro Brain Natriuretic Peptide) Levels
Difference in the change of nt-proBNP (N terminales pro brain natriuretic peptide) levels between treatment groups from randomization to week 26
Time frame: 26 weeks
Changes in Ejection Fraction
Difference in the change of ejection fraction between treatment groups from randomization to week 26 Ejection fraction was measured by ultrasound.
Time frame: 26 weeks
Changes in Left Ventricular End-diastolic Volume
Difference in the change of left ventricular end-diastolic volume from randomization to week 26 (measured by ultrasound)
Time frame: 26 weeks
Duration of Hospital Stay
Difference in the duration of hospital stay between the treatment groups after initiation of the study treatment. This outcome measure includes all days of an inpatient stay in a hospital after the initial discharge.
Time frame: 30 weeks
Changes in E/è Ratio From Baseline to Week 26
E/E' ratio is a measure of left ventricular filling pressure. The E/e' ratio is a parameter for diastolic function assessment that is frequently used for Heart failure with preserved ejection fraction evaluation. To derive the E/e´ ratio one must divide the maximum velocity of the E-wave of mitral valve inflow by the maximal velocity of E. In normal individuals the E/e´ ratio is \<8. In the presence of diastolic dysfunction / impaired relaxation, e´ will be rather low. In contrast, the E-wave increases with elevated filling pressures. Thus the E/e´ ratio will increase in the presence of diastolic dysfunction. An E/e´ratio \>14 is highly suggestive of elevated filling pressures.
Time frame: From Baseline to Week 26
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Kardinal schwarzenberg Klinikum Schwarzach
Schwarzach im Pongau, State of Salzburg, Austria
Kepler Universitätsklinikum Linz
Linz, Upper Austria, Austria
VIVIT Institut am akademischen Lehrkrankenhaus Feldkirch
Feldkirch, Vorarlberg, Austria
Landeskrankenhaus Graz II Standort West
Graz, Austria
Medical University of Graz
Graz, Austria
Uniklinikum Salzburg
Salzburg, Austria
Krankenanstalt Rudolfstiftung
Vienna, Austria
...and 1 more locations
Changes in Left Ventricular End-systolic Volume (LVESV) From Baselin to Week 26
End-systolic volume (ESV) is the volume of blood in a ventricle at the end of contraction, or systole, and the beginning of filling, or diastole. Left ventricular end-systolic volume (LVESV) was measured at baseline and after 26 weeks by echocardiography.
Time frame: Baseline to Week 26