Comparative efficacy of renin-angiotensin system modulators on prognosis and right heart functional parameters in patients with chronic heart failure and preserved left ventricular systolic function

Abstract

The aim of study was to compare efficacy of long-term therapy with ramipril (R, 10 mg), spironolacton (S, 50 mg), valsartan (V, 320 mg) and aliskiren (A, 300 mg) on prognosis, right ventricular (RV) and atrial (RA) parameters, BNP and high sensitivity C-reactive protein (CRP) levels in pts with III-IV NYHA FC CHF and preserved left ventricular ejection fraction (PEF). Methods: 101 pts (age 63.2+1.4) with PEF were randomly assigned to groups A (n=26, receiving only R), B (n=26, receiving S), C (n=26, receiving V) and D (n=24, receiving A) in addition to R, diuretics and beta-blockers. Assessment of RV fractional area changes (FAC), tricuspid annulus plane systolic excursion (TAPSE), transtricuspidal E/A ratio, RA contraction fraction (CF), functional index (FI), kinetic energy (KE), pulmonary artery ejection time (PAET), BNP and CRP levels was performed at baseline, 3, 6, 12, 24 and 36 months. Results: 1-, 2- and 3-year mor-tality (%) were 30.8, 38.5 and 46.2 in group A; 23.1, 30.8 and 38.5 in group B; 28, 36 and 44 in group C and 16.7, 25 and 33.3 in group D. Survival analysis revealed lower pro-ba-bi-li-ty (RR reduction, %) of 1-year at 25 and 45.8, 2-year at 20 and 42.9 and 3-year mortality at 16.7 and 28.6 in pts, treated with S (p<0.05) and A (p<0.01), respectively, compared to group A. R use significantly improved (% from baseline) BNP at 23, CRP at 40.9, E/A ratio at 18.3, RA FI at 30.2, KE at 47.7, CF at 16.3, PAET at 9.5 after 6 months, TAPSE at 28.5 and RV FAC at 21.3 after 12 months. R+S therapy significantly changed BNP at 22.1, CRP at 37.9, RA FI at 27.3, KE at 50.6 after 3 months, E/A ratio at 26.1, CF at 21.1, PAET at 10.9 after 6 months, TAPSE at 29 and FAC at 21.6 after 12 months. R+V use improved CRP at 44.8, E/A ratio at 19.1, RA FI at 20.9, KE at 48.8 after 3 months, CF at 16.3, PAET at 10.9, BNP at 24.6 after 6 months, TAPSE at 31.9 and RV FAC at 22.4 after 12 months. R+A therapy significantly improved BNP at 25.5, CRP at 40.7, E/A ratio at 20.4, RA FI at 25, KE at 55.7, CF at 19.4, PAET at 10.8 after 3 months, TAPSE at 29.7 and RV FAC at 21.2 after 6 months. Reduction from baseline of BNP and CRP values >50% after 12 months associated with significant (p<0.01) improvement of prognosis compared to decrease of BNP and CRP<30% (RR 0.35 and 0.32), respectively Conclusions: 1) Decrease of BNP and CRP>50% after 12 months identified pts with cardiac risk reduction. 2) S and A treatment reduced mortality in pts with CHF and PEF 3) A use associated with lower mortality due to highly expressed improvement of RV and RA functional parameters, neurohormonal and inflammation status.