TABLE 1.
Clinical trials associated with sGC inhibitors and neprilysin inhibitors.
| Study | Drugs | meanEF (%) | Number | Female (%) | NPs (pg/ml) | Outcomes | Notes |
|---|---|---|---|---|---|---|---|
| McMurray et al. (2014), PARADIGM-HF | Sacubitril- Valsartan (LCZ696) | 29.6 | 4187 | 21.0 | BNP 255 NT-proBNP 1631 | A composite of death from CVD or hospitalization 21.8% vs 26.5% HR 0.80, 95% CI 0.73 to 0.87, p < 0.001 | |
| enalapril | 29.4 | 4212 | 22.6 | BNP 251 NT-proBNP 1594 | |||
| Velazquez et. al. (2019) PIONEER-HF | Sacubitril- Valsartan | 24 | 440 | 25.7 | NT-proBNP 4821 | The time-averaged reduction in the NT-proBNP at weeks 4 and 8 to the baseline -46.7% vs -25.3%(ratio of change 0.76, 95% CI 0.69 to 0.85) | |
| enalapril | 25 | 441 | 30.2 | 4710 | |||
| Solomon et al. (2019) PARAGON-HF | Sacbitril- Vaslsartan | 57.6 | 2419 | 51.6 | NT-proBNP 904 | Cardiovascular death 8.5% vs 8.9% HR 0.95, 95% CI 0.79 to 1.16 | A composite outcome of hospitalization and cardiovascular death in female RR 0.73 95% CI 0.59 to 0.90 |
| Valsartan | 57.5 | 2403 | 51.8 | 915 | Total Hospitalization 690 vs 797 HR 0.85, 95% CI 0.72 to 1.0 | ||
| Pieske et al. (2021) PARALLAX | acbitril-Vaslsartan | 56.7 | 1286 | 50.2 | NT-proBNP 786 | The reduction in NTproBNP at week 12 The adjusted geometric mean ratio 0.84 (95% CI, 0.80- 0.88; p < 0.001) | No significant between-group difference in the Kansas City Cardiomyopathy Questionnaire clinical summary score 12.3 vs 11.8 ( mean difference, 0.52; 95% CI, −0.93 to 1.97) |
| No improvement in NYHA class 23.6% vs 24.0% of patients (adjusted odds ratio, 0.98; 95% CI, 0.81 to 1.18) | |||||||
| Individualized comparator | 56.2 | 1286 | 51.2 | 760 | 6-minute walk difference at week 24. | 6-minute walking distance improved among women but decreased among men 6.59 vs −12.07 (p = 0.0024) | |
| No significant between-group from baseline 9.7 m vs 12.2 m | |||||||
| (adjusted mean difference, −2.5 m; 95% CI, −8.5 to 3.5; p = 0.42) | Individualized comparator: enalapril at a target dose of 10, valsartan at a target dose of 160 mg, or placebo (no RAS inhibitor). | ||||||
| Armstrong et al. (2020a) VICTORIA | Vericiguat | 29.3 | 2526 | 24.0 | NT-proBNP 2803 | The composite of death from any cause or hospitalization for heart failure | |
| 37.9% vs 40.9% | |||||||
| HR 0.90, (95% CI 0.83 to 0.98, p = 0.02) | |||||||
| Placebo | 27.9 | 2524 | 23.9 | 2821 | |||
| Udelson et al. (2020) CAPACITY HFpEF | Praliciguat | 61.9 | 91 | 38.5 | NT-proBNP 260 | Changes in peak VO2 | |
| −0.26 vs −0.04 mL/kg/min | |||||||
| 1286 (95% CI, −0.83 to 0.31 and –0.49 to 0.56) | |||||||
| Placebo | 59.8 | 90 | 44.4 | 228.5 | |||
| Armstrong et al. (2020b) VITALITY-HFpEF | Vericiguat 15 mg | 56.8 | 264 | 53.0 | NT-proBNP 1364.5 | The mean changes in the KCCQ PLS | The overall mortality rate was 4.1% (n = 32) |
| 5.5 points in the 15-mg/d vericiguat group | 10 (3.8%) in the 15-mg vericiguat group | ||||||
| 6.5 points in the 10-mg/d vericiguat group | 15 (5.7%) in the 10 mg vericiguat group | ||||||
| 6.9 points in the placebo group | 7 (2.7%) in the placebo group | ||||||
| 8 cardiovascular deaths (3.0%) in the 15-mg vericiguat group | |||||||
| Vericiguat 10mg | 55.8 | 263 | 47.1 | 1339.1 | differences between either vericiguat dosage and placebo were not statistically significant | 12 (4.6%) in the 10-mg vericiguat group | |
| Placebo | 56.3 | 262 | 46.2 | 1644.2 | 4 (1.5%) in the placebo group |