[Is triple combination of different neurohormonal modulators recommended for treatment of mild-to-moderate congestive heart failure patients? (Results of Sadko-CHF study)].
OBJECTIVE
To assess effects of different variants of neurohormonal (NH) modulation with angiotensin converting enzyme (ACE-I) quinapril (Q), angiotensin-receptor blocker (ARB) valsartan (V) and their combination in addition to beta-adrenergic blocker bisoprolol (B) on functional status, quality of life (QOL), parameters of left ventricular (LV) remodeling, main indices of 24-h heart rate variability (HRV) and NH profile in patients with stable mild-to-moderate congestive heart failure (CHF).


METHODS
Sixty three patients with CHF (NYHA class II-III) as a result of ischemic heart disease and dilated cardiomyopathy with LV EF < 40% were randomly assigned to one of the treatment variants on 1:1:1 basis: B+Q (n = 22), B+V (n = 23) and combination of B+Q + V (n = 18). At baseline, all the patients in this study were on background B treatment and according to the study design Q or V were then added to B at randomization. NYHA FC, 6-min walking test (6MT), QOL, 2D-echocardiography, plasma renin activity (PRA), angiotensin II (AT-II), aldosterone (Ald), norepinephrine (NE), epinephrine (E), brain natriuretic peptide (BNP) concentrations and 24-hour HRV parameters were investigated at baseline, 3 and 6 months after randomization.


RESULTS
During the study NYHA FC improvement was revealed in all three treatment groups with comparative significant changes in 6MT distance by 20.4%, 19.1% and 19.4% in B+Q, B+V and B+Q+V groups, respectively. QOL maximally decreased in B+V combination (from 45 to 21 points). LV volumes significantly decreased and LV ejection fraction (EF) increased in all groups to the end of the study. Triple combination had no additional effect on LV volumes and LVEF changes compared to B+Q and B+V groups. Plasma NE concentrations decreased maximally in B+Q group (from 650 to 430 pg/ml, p = 0.007). The lesser effect was observed in the combination of B+Q+V, with any NE changes in B+ V group. The E concentration increased significantly (from 215 to 295 pg/ml, p = 0.024) in the B+Q+V group at the end of the study. Plasma A-II concentration did not differ from the baseline during the study in B+Q group, but significantly increased in B+V group and maximally in B+Q+V group (from 11.4 to 23.5 pg/ml, p = 0.009). To the end of the study plasma Ald concentrations remain reduced significantly only in B+V group. The level of BNP significantly decreased in all 3 treatment groups. Significant changes in HRV indices, both in time and frequency domain, were revealed in the B+Q group at 3-month follow-up and SDNN increased on month 24 (p = 0.039). These changes became insignificant at the end of the study. The lesser effect was revealed in B+Q+V group, with insignificant trend toward an increase of SDNN to the end of the study. HRV indices did not improve in the B+V group.


CONCLUSIONS
During long-term treatment the triple combination of B+Q+ V has no significant advantages over B+Q and B+V by the functional status, QOL and parameters of LV remodeling in patients with mild-to-moderate CHF. The combination of B+Q has more potent effect on 24-hour HRV parameters, sympatho-adrenal activity and renal function compared to B+V and B+Q+V groups in CHF patients in our study. The combination B+Q+V may have a negative effect on NH profile (excessive activation of ATII and E) in CHF patients. The triple combination is not recommended for therapy of stable mild-to-moderate CHF patients.
Skvortsov
A A
AA
Mareev
V Iu
VIu
Nasonova
S N
SN
Sychev
A V
AV
Arbolishvili
G N
GN
Baklanova
N A
NA
Masenko
V P
VP
Belenkov
Iu N
IuN
D000319:Adrenergic beta-Antagonists / Q000627:therapeutic use; D000328:Adult; D000368:Aged; D047228:Angiotensin II Type 1 Receptor Blockers / Q000627:therapeutic use; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use; D015415:Biomarkers / Q000097:blood; D017298:Bisoprolol / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D015716:Electrocardiography, Ambulatory; D005080:Exercise Test; D005260:Female; D005500:Follow-Up Studies; D006333:Heart Failure / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D011788:Quality of Life; D000077583:Quinapril; D013318:Stroke Volume; D044005:Tetrahydroisoquinolines / Q000627:therapeutic use*; D013777:Tetrazoles / Q000627:therapeutic use*; D016896:Treatment Outcome; D014633:Valine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000068756:Valsartan
D000319:Adrenergic beta-Antagonists; D047228:Angiotensin II Type 1 Receptor Blockers; D000806:Angiotensin-Converting Enzyme Inhibitors; D015415:Biomarkers; D044005:Tetrahydroisoquinolines; D013777:Tetrazoles; D000068756:Valsartan; D014633:Valine; D000077583:Quinapril; D017298:Bisoprolol