Table 2. Primary and secondary outcomes in clinical trials of sacubitril/valsartan, dapagliflozin, empagliflozin, vericiguat and omecamtiv mecarbil.
| Variables | PARADIGM-HF | PIONEER-HF | DAPA-HF | EMPEROR-Reduced | VICTORIA | GALACTIC-HF | |
|---|---|---|---|---|---|---|---|
| Trial characteristics | |||||||
| Investigated medication | Sacubitril/valsartan | Sacubitril/valsartan | Dapagliflozin | Empaglflozin | Vericiguat | Omecamtiv mecarbil | |
| Comparator | Enalapril | Enalapril | Placebo | Placebo | Placebo | Placebo | |
| No. of patients enrolled | 8,442 | 881 | 4,744 | 3,730 | 5,050 | 8,256 | |
| Median follow up | 27 months | 8 weeks | 18.2 months | 16 months | 10.8 months | 21.8 months | |
| Primary outcome | |||||||
| Death from CV causes or hospitalization for HF | Time-averaged proportional change in NT-proBNP | WHF (hospitalization or an urgent visit resulting in intravenous therapy for HF) or CV death | CV death or hospitalization for WHF | Death from CV causes or first hospitalization for HF | First HF event (hospitalization or urgent visit for HF) or death from CV causes | ||
| HR, 0.80; 95% CI, 0.73–0.87; p<0.001 | - | HR, 0.74; 95% CI, 0.65–0.85; p<0.001 | HR, 0.75; 95% CI,0.65–0.86; p<0.001 | HR, 0.90; 95% CI, 0.82–0.98; p=0.02 | HR, 0.92; 95% CI, 0.86–0.99; p=0.03 | ||
| Secondary outcomes | |||||||
| Death from CV causes | HR, 0.79; 95% CI, 0.71–0.89; p<0.001 | - | HR, 0.82; 95% CI, 0.69–0.98; p=0.03 | HR, 0.92; 95% CI, 0.75–1.12; p<0.001 | HR, 0.93; 95% CI, 0.81–1.06 | HR, 1.01; 95% CI, 0.92–1.11 | |
| First HF hospitalization | HR, 0.79; 95% CI, 0.71–0.89; p<0.001 | HR, 0.56; 95% CI, 0.37–0.84 | HR, 0.70; 95% CI, 0.59–0.83; p<0.001 | HR, 0.70; 95% CI, 0.58–0.85, p<0.001) | HR, 0.90; 95% CI, 0.81–1.00 | HR, 0.95; 95% CI, 0.87–1.03 | |
| Death from any cause | HR, 0.84; 95% CI, 0.76–0.93; p<0.001 | HR, 0.66, 95% CI, 0.30–1.48 | HR, 0.83; 95% CI, 0.71–0.97; p=0.02 | HR, 0.92; 95% CI, 0.77–1.10 | HR, 0.95; 95% CI, 0.84–1.07; p=0.38 | HR, 1.00; 95% CI, 0.92–1.09 | |
| Change in KCCQ* | At 8 months; 1.64 (0.63–2.65), p=0.001 | - | At 8 months; 1.18 (1.11–1.26), p<0.001 | At 13 months;1.7 (0.5–3.0) | - | At 3 months; inpatients: 2.5 (0.5–4.5), outpatients: −0.5 (−1.4, 0.5), p=0.03 by joint omnibus F-testing | |
| Worsening renal function | †HR, 0.86; 95% CI, 0.65–1.13; p=0.28 | †RR, 0.93; 95% CI, 0.67–1.28 | †HR, 0.71; 95% CI, 0.44–1.16; p=0.17 | ‡HR, 0.50; 95% CI, 0.32–0.77 | - | - | |
CV = cardiovascular; HF = heart failure; NT-proBNP = N-terminal pro-brain natriuretic peptide; WHF = worsening heart failure; HR = hazard ratio; CI = confidence interval; KCCQ = The Kansas City Cardiomyopathy Questionnaire ; eGFR = estimated glomerular filtration rate; GFR = glomerular filtration rate.
*Between group difference; †Decline in renal function defined as end-stage renal disease or 50% eGFR decline from randomization or decrease of eGFR of more than 30 mL/min/1.73 m2 to less than 60 mL/min/1.73 m2; ‡The composite renal outcome includes chronic dialysis or renal transplantation or a sustained reduction of 40% or more in the estimated GFR or a sustained estimated GFR of less than 15 mL/min/ 1.73 m2 in patients with a baseline estimated GFR of 30 mL/min/1.73 m2 or more or a sustained estimated GFR of less than 10 mL/min/1.73 m2 in those with a baseline estimated GFR of less than 30 mL/min/1.73m2.