Introduction
Methods
Trial design
Patient enrolment and randomization
Trial procedures
Study endpoints
Statistical analysis
Results
Cohort characteristics at baseline
Placebo | Empagliflozin | P-value | |
---|---|---|---|
Sample size (n) | 71 | 71 | |
Age [years] (SD) | 68.5 ± 8.0 | 69.3 ± 7.4 | 0.53 |
Sex [female]—[%] (n) | 12.7% (9) | 15.5% (11) | 0.81 |
Heart rate [bpm] (SD) | 68.6 ± 10.4 | 68.3 ± 10.5 | 0.85 |
Blood pressure—Systolic [mmHg] (SD) | 132.8 ± 15.9 | 134.5 ± 15.9 | 0.53 |
—Diastolic [mmHg] (SD) | 76.1 ± 9.3 | 77.4 ± 9.2 | 0.38 |
Body Mass Index [kg/m2] (SD) | 31.8 ± 4.8 | 31.9 ± 4.7 | 0.85 |
NT-proBNP [pg/ml] (IQR) | 129 (53/353) | 142 (59/268) | 0.96 |
Traditional cardiovascular risk factors | |||
Arterial Hypertension—[%] (n) | 94.4% (67) | 84.5% (60) | 0.099 |
Diabetes mellitus—[%] (n) | 100% (71) | 100% (71) | 1.0 |
Insulin-dependent diabetes mellitus—[%] (n) | 45.1% (32) | 50.7% (36) | 0.61 |
HbA1c [%] (IQR) | 7.4 (7.0/8.2) | 7.3 (7.0/7.7) | 0.30 |
Dyslipidemia—[%] (n) | 90.1% (64) | 84.5% (60) | 0.45 |
Family history of MI and/or stroke—[%] (n) | 32.4% (23) | 28.2% (20) | 0.72 |
Obesity—[%] (n) | 57.7% (41) | 64.8% (46) | 0.49 |
Smoking—[%] (n) | 15.5% (11) | 12.7% (9) | 0.81 |
Comorbidities | |||
Atrial fibrillation—[%] (n) | 29.9% (20) | 23.2% (16) | 0.44 |
Chronic kidney disease—[%] (n) | 20.0% (14) | 13.0% (9) | 0.36 |
Chronic obstructive pulmonary disease—[%] (n) | 5.6% (4) | 7.1% (5) | 0.74 |
Chronic heart failure—[%] (n) | 26.8% (19) | 15.5% (11) | 0.15 |
Coronary artery disease—[%] (n) | 44.1% (30) | 35.9% (23) | 0.38 |
History of myocardial infarction—[%] (n) | 37.1% (26) | 23.2% (16) | 0.098 |
History of TIA/Stroke—[%] (n) | 9.6% (7) | 7.1% (5) | 0.77 |
Peripheral artery disease—[%] (n) | 11.9% (8) | 10.1% (7) | 0.79 |
Venous thromboembolism—[%] (n) | 10.0% (7) | 7.1% (5) | 0.76 |
Echocardiography | |||
Lateral E/e´ ratio (IQR) | 9.1 (8.1/10.3) | 9.9 (8.4/11.9) | 0.031 |
LVEF [%] (SD) | 57.9 ± 5.7 | 59.2 ± 5.5 | 0.19 |
Left ventricular mass index [g/m2.7] (SD) | 95.2 ± 25.0 | 94.6 ± 26.9 | 0.90 |
Effect of empagliflozin compared to placebo on left ventricular diastolic function
Additional study endpoints
After 1 week of treatment | After 12 weeks of treatment | |||
---|---|---|---|---|
Beta-estimate (95% CI) | P-value | Beta-estimate (95% CI) | P-value | |
Cardiac biomarkers | ||||
Left ventricular ejection fractiona [%] | 0.4 (– 0.8; 1.6) | 0.48 | – 0.3 (– 1.5; 0.9) | 0.62 |
Left ventricular end-diastolic volumea [ml] | – 3.1 (– 8.1; 1.9) | 0.23 | 1.1 (– 4.9; 7.1) | 0.71 |
Left ventricular mass index [g/m2.7] | – 3.9 (– 9.9; 2.1) | 0.20 | – 0.8 (– 7.3; 5.8) | 0.82 |
Relative wall thickness | – 0.005 (– 0.029; 0.02) | 0.72 | 0.00351 (– 0.023; 0.0301) | 0.80 |
NT-proBNPa [pg/ml] | – 0.23 (– 0.30; – 0.06) | 0.009 | – 0.01 (– 0.195; 0.175) | 0.91 |
Troponina [pg/ml] | 0.09 (– 0.05; 0.22) | 0.21 | – 0.071 (– 0.188; 0.0458) | 0.24 |
Circulation | ||||
Blood pressure—Systolic [mmHg] | – 4.53 (– 8.13; – 0.92) | 0.015 | – 3.39 (– 7.37; 0.60) | 0.098 |
Diastolic [mmHg] | – 3.05 (– 5.05; – 1.05) | 0.0034 | – 1.38 (– 3.35; 0.582) | 0.17 |
Heart rate [bpm] | – 0.53 (– 2.63; 1.57) | 0.62 | – 0.16 (– 3.23; 2.92) | 0.92 |
Metabolic biomarkers | ||||
Body mass index [kg/m2] | – 0.42 (– 0.59; – 0.24) | < 0.0001 | – 0.71 (– 0.99; – 0.44) | < 0.0001 |
C-reactive proteina [mg/L] | 0.787 (– 0.122; 0.279) | 0.44 | – 0.185 (– 0.459; 0.089) | 0.19 |
Fatty liver index | – 0.516 (– 2.45; 1.29) | 0.55 | – 2.12 (– 4.81; 0.564) | 0.12 |
HbA1c [%] | – 0.001 (– 0.072; 0.069) | 0.97 | – 0.43 (– 0.62; – 0.23) | < 0.0001 |
Uric acid [mg/dL] | – 1.01 (– 1.28; – 0.75) | < 0.0001 | – 0.66 (– 1.01; – 2.96) | 0.0005 |
Hematological biomarkers | ||||
Leukocyte count [/nL] | 0.39 (0.05; 0.72) | 0.027 | – 0.19 (– 0.58; 0.20) | 0.34 |
Red blood cell count [/pL] | 0.11 (0.04; 0.17) | 0.002 | 0.29 (0.20; 0.38) | < 0.0001 |
Hemoglobin [g/dL] | 0.24 (0.06; 0.42) | 0.01 | 0.82 (0.55; 1.09) | < 0.0001 |
Mean corpuscular hemoglobin [pg] | – 0.21 (– 0.42; – 0.004) | 0.048 | – 0.13 (– 0.40; 0.14) | 0.34 |
Mean corpuscular hemoglobin concentration [g/L] | – 0.28 (– 0.52; – 0.04) | 0.026 | – 0.36 (– 0.61; – 0.12) | 0.005 |
Mean corpuscular volume [fL] | 0.02 (– 0.36; 0.40) | 0.92 | 0.50 (– 0.13; 1.12) | 0.12 |
Hematocrit [%] | 1.05 (0.45; 1.65) | 0.0009 | 2.91 (2.09; 3.73) | < 0.0001 |
Thrombocyte count [/nL] | 8.99 (1.22; 16.8) | 0.025 | – 5.34 (– 13.6; 2.94) | 0.21 |
Beta-estimateEmpagliflozin 10 mg/day vs. Placebo [95% CI] | P-value | |
---|---|---|
Basic modela | – 1.18 [– 1.72; – 0.65] | < 0.0001 |
+ ∆ Hemoglobin | – 0.95 [– 1.54; – 0.36] | 0.0021 |
+ ∆ Hematocrit | – 1.04 [– 1.66; – 0.43] | 0.0012 |
+ ∆ Estimated glomerular filtration rate | – 1.09 [– 1.63; – 0.55] | 0.00013 |
+ ∆ Body mass index | – 1.11 [– 1.69; – 0.52] | 0.00031 |
+ ∆ Systolic blood pressure | – 1.14 [– 1.68; – 0.59] | < 0.0001 |
+ ∆ Diastolic blood pressure | – 1.16 [– 1.71; – 0.61] | < 0.0001 |
+ ∆ HbA1c | – 1.17 [– 1.74; – 0.60] | 0.0001 |
+ ∆ NT-proBNP | – 1.19 [– 1.74; – 0.64] | < 0.0001 |
+ ∆ Uric acid | – 1.19 [– 1.75; – 0.63] | < 0.0001 |
Full modelb | – 0.77 [– 1.52; – 0.02] | 0.046 |