The aim of study was to compare efficacy of therapy with ramipril (R, 10 mg) + spironolacton (S, 25 mg), valsartatan (V, 320 mg) + S, sacubitril/valsartan (S/V, 97/103 mg), and S/V+S on prognosis, left (LV) and right ventricular (RV) and atrial (LA) and (RA) functional parameters, NT-pro-BNP (pg/ml), transforming growth factor-beta (TGF-β) and hsCRP (ng/ml) levels in patients (pts) with III NYHA FC heart failure in relation to reduced (HFrEF), mid-ranged (HFmEF) or preserved (HFpEF) ejection fraction (EF).
Methods
122 pts (age 58.4) with HFrEF (EF<50), 108 pts (age 59.9) with HFmEF (40≤EF<50) and 104 pts (age 63.1) with HFpEF (EF≥50) in sinus rhythm were randomly assigned to groups, receiving R+S (n=32; 28; 27), V+S (n=30; 27; 26) and S/V (n=31; 27; 26) and S/V+S (n=29; 26; 25) in addition to diuretics and beta-blockers.
Results
1-year mor-tality and hospitalization (%) were, 40.6 and 73.3; 39.3 and 57.1; 33.3 and 55.5 in R+S; 43.3 and 76.7; 40.7 and 59.3; 38.5 and 57.7 in V+S; 32.3 and 58.1; 29.6 and 48.1 and 30.1 and 42.3 in S/V and 31 and 55.2; 30.8 and 42.3 and 32 and 40 in S/V+S receiving groups with HFrEF, HFmEF and HFpEF, respectively.
Survival analysis revealed RR reduction of 1-year mortality at 20.7 and 23.6; 25.4 and 28.4 and hospitalization at 20.7 and 24.3; 24.7 and 29.3 in HFrEF pts, treated by S/V and S/V+S, compared to R+S and V+S, respectively (p<0.05). Similarly, 1-year mortality and hospitalization were reduced at 24.7 and 21.6; 27.3 and 24.3 in HFmEF pts. Significant reduction of 1-year hospitalization at 23.8 and 23.7; 27.9 and 30.7 (p<0.05), but not mortality was revealed in V/S and V/S+S treatment group with HFpEF. 1-year S/V and S/V+S treatment significantly (at % from baseline, p<0.01) decreased levels of TGF-β at 32.3 and 34.5; 31.3 and 33.3, NT-pro-BNP at 40.3 and 42.3 and 38.9 and 40.1, e' at 30.6 and 31.5; 30.2 and 30.6,Ar-A at 56.6 and 58.8; 55.1 and 57.2, RAFI at 34.3 and 35.1; 32.9 and 33.6, LAFI at 35.7 and 36.6; 34.9 and 35.2, LV EF at 23.1 and 24.2; 22.1 and 23.4 in pts with HFrEF and HFmEF, and significant changes of hsCRP at 34.6 and 35.2, levels of TGF-β at 30.2 and 31.2, TAPSE at 42.2 and 43.4, e' at 26.2 and 28.2, PA ET at 19.8 and 20.3 in pts with HFpEF, compared to R+S and V+S, respectively.
Conclusions
1) S/V and S/V+S treatment associated with significant reduction of morbidity and mortality in pts with HFrEF and HFmEF, and hospitalization in HFpEF compared to use of R+S and V+S. 2) Changes of NT-pro-BNP, Ar-A, RAFI and LAFI, e' ≥40%, TGF-β ≥30% identified pts with cardiovascular risk reduction in HFrEF and HFmEF groups, while changes of TGF-β, hsCRP≥30%; PAET ≥30% revealed pts with improvement of morbidity in pts with HFpEF. 3) Prognostic improvement in pts treated by S/V and S/V+S has related to improvement of TGF-β, LV systolic and diastolic functional parameters, LA and RA functional parameters in HFrEF and HFmEF and to TGF-β, hsCRP, LV diastolic and RV functional parameters changes in HFpEF.
