TABLE 1.
The design of the study and the main results of the DAPA‐HF, 4 EMPEROR‐reduced 5 and SOLOIST 6 trials are summarised
|
DAPA‐HF 4 (n = 4,744) |
EMPEROR‐reduced 5 (n = 3,730) |
SOLOIST 6 (n = 1,222) |
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|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Dapagliflozin 10 mg o.d. vs. placebo | Empagliflozin 10 mg o.d. vs. placebo | Sotagliflozin 200 mg o.d. up‐titrated to 400 mg o.d. vs. placebo | ||||||||||
| Clinical setting | ||||||||||||
| Outpatients | Outpatients | Inpatients or outpatients (pre‐ or post‐discharge) | ||||||||||
| Main inclusion criteria | ||||||||||||
| With and without T2DM | With and without T2DM | With T2DM | ||||||||||
| Diagnosis of HFrEF (≥2 months) with NYHA classes II–IV | Diagnosis of HFrEF (≥3 months) with NYHA II–IV | Hospitalisation due to acute decompensated heart failure | ||||||||||
| LVEF ≤40% in the last 12 months | LVEF ≤40% in the last 6 months | No need for oxygen therapy, intravenous inotropic or vasodilator (excluding nitrates) or diuretic therapy. | ||||||||||
|
hHF (last 12 months) Yes No |
If AF |
hHF (last 12 months) Yes No |
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| NT‐proBNP | >400 | >600 | >900 |
NT‐proBNP
|
SR AF |
≥600 >1,200 |
≥2,500 ≥5,000 |
BNP |
SR AF |
≥150 >450 |
||
|
SR AF |
≥600 >1,200 |
≥1,000 ≥2,000 |
NT‐proBNP |
SR AF |
≥600 >1,800 |
||||||
|
SR AF |
≥600 >1,200 |
≥600 >1,200 |
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|
Optimal treatment, stable in the last ≥4 weeks (ACEI, ARB or ARNI; beta‐bloccanti, MRA) |
Optimal treatment, stable in the last ≥1 weeks (ACEI, ARB or ARNI; beta‐bloccanti, MRA) | |||||||||||
| Main exclusion criteria | ||||||||||||
| History of hypotension or systolic arterial pressure <95 mm Hg | History of hypotension or systolic arterial pressure <100 mm Hg | Systolic arterial pressure <100 mm Hg | ||||||||||
| eGFR <30 mL/min/1.73 m2 | eGFR <20 mL/min/1.73 m2 | eGFR <30 mL/min/1.73 m2 | ||||||||||
| Follow‐up (median) | ||||||||||||
| 18.2 months | 16 months | 9 months | ||||||||||
| Main results | ||||||||||||
|
Primary end point: ‐ CV death and hHF or urgent HF visit: ARR: 4.9 × 100 patients/year HR, 0.74 (95% CI, 0.65‐0.85); P <.001 Main secondary end points: ‐ Total number of hHF: HR, 0.75 (95% CI, 0.65‐0.88); ˆ < 0.001 ‐ CV death: HR, 0.82 (95% CI, 0.69‐0.98); p: NA ‐ All‐cause death: HR, 0.83 (95% CI, 0.71‐0.97); p: NA |
Primary end point: ‐ total number CV death and hHF: ARR, −5.3 × 100 patients/year HR, 0.75 (95% CI, 0.65‐0.86); P <.001 Secondary end points: ‐ Total number hHF: HR, 0.70 (95% CI, 0.58‐0.85); P <.001 ‐ Mean slope of change in eGFR (mL/min/1.73 m2) per year: absolute difference 1.73 (95% CI, 1.10‐2.37); P <.001 Other analysed end points: ‐ CV death: HR, 0.92 (95% CI, 0.75‐1.12); p: NA ‐ All‐cause death: HR, 0.92 (95% CI, 0.77‐1.10); p: NA |
Primary end point: ‐ total number CV death and hHF or urgent HF visit: ARR: −25.3 × 100 patients/year HR, 0.67 (95% CI, 0.52‐0.85); P <.001 Main secondary end points: ‐ Total number HF hospitalisation or urgent visit: HR, 0.64 (95% CI, 0.49‐0.83); HR, P <.001 ‐ CV death: HR 0.84 (95% CI, 0.58‐1.22); P =.36 ‐ All‐cause death: HR, 0.82 (95% CI, 0.59‐1.14); p: NA |
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| Non‐HF‐related adverse events | ||||||||||||
|
Dapagliflozin vs. placebo: ‐ symptoms of volume depletion 7.5% vs. 6.8% |
Empagliflozin vs. placebo: ‐ Hypotension: 9.4% vs. 8.7% ‐ Genital infections 1.7% vs. 0.6% |
Sotagliflozin vs. placebo ‐ Hypotension 6.0% vs. 4.6% ‐ Diarrhoea 6.1% vs. 3.4% ‐ Severe hypoglycaemia 1.5% vs. 0.3% |
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Abbreviations: ACEi, ACE inhibitor; AF, atrial fibrillation; ARB, angiotensin II receptor blocker; ARNi, angiotensin receptor neprilysin inhibitor; ARR, absolute risk reduction; CI, confidence interval; GFR, estimated glomerular filtration rate; hHF, hospitalisation for heart failure; HR, hazard ratio; LVEF, left ventricular ejection fraction; MRA, mineralocorticoid receptor antagonists; NA, not available; NT‐proBNP, N‐terminal pro‐brain natriuretic peptide; SR, sinus rhythm; T2DM, type 2 diabetes mellitus.