[Combined therapy with quinapril, an ACE inhibitor, and valsartan, a type 1 angiotensin II receptors blocker, for moderate chronic cardiac failure may raise the degree of neurohormonal block and improve 24-h heart rate variability compared to the effect of monotherapy (data from the trial SADKO-CHF)].
OBJECTIVE
To compare effects of various regimens of long-term monotherapy with quinapril (an ACE inhibitor) and valsartan (a type 1 angiotensin II receptors blocker) and combined therapy with these drugs on the activity of heurohormonal systems and 24-h heart rate variability (HRV) in patients with stable moderate chronic cardiac failure (CCF).


METHODS
A total of 80 patients with FC II-III CCF secondary to coronary heart disease (CHD), delated cardiomyopathy (DCMP) and decompensated hypertensive heart (49%/47%/4%) were randomized into 3 groups. Group 1 patients (n = 28) received quinapril, group 2 (n = 26)--valsartan, group 3 (n = 26)--quinapril + valsartan. The levels of norepinephrine (NE), angiotensin II (AT II), activity of plasmic renin (PR), aldosteron (AS), plasmic cerebral sodiumuretic peptide (CSUP) were measured and ECG with determination of HRV and heart rate disturbances was made before and 3, 6 months after the treatment.


RESULTS
NE concentration lowered most significantly in group 1 (from 630 to 405 pg/ml) vs groups 2 and 3 (from 525 to 490 pg/ml and from 525 to 480 pg/ml, respectively). A 6-month treatment induced significant changes neither in concentrations of AT II nor AC. ATII concentrations rose 2-fold in group III (from 11.9 to 24.3 pg/ml) under a parallel rise of PR activity from 0.7 to 2.5 ng/ml/h and a fall in AS level from 132 to 83 pg/ml. In group 2 AS diminished also (from 165 to 126 pg/ml). CSUP decreased in all the groups, but significantly only in groups II and III (from 350 to 237 and 322 to 204 pg/ml after 6 months of treatment, respectively). Significant changes of 24-h HRV (both spectral and temporary) were observed in group 1 after 3 months of treatment. These changes lost significance to the end of the treatment. In groups 2 and 3 the changes were less pronounced.


CONCLUSIONS
Quinapril is more potent than valsartan and quinapril + valsartan combination in relation to activity of sympathico-adrenal system and HRV in patients with moderate stable CCF. Long-term therapy with valsartan does not improve parameters of HRV in moderate CCF. If CCF patients take quinapril for a long time, they develop the effect of disappearing block of AS synthesis and reactivation of A TII production. The best mechanism of long-term control over the activity of renin-angiotensin-aldosteron system in patients with moderate CCF is combination of quinapril with valsartan.
Skvortsov
A A
AA
Nasonova
S N
SN
Sychev
A V
AV
Arbolishvili
G N
GN
Baklanova
N A
NA
Mareev
V Iu
VIu
Belenkov
Iu N
IuN
D000328:Adult; D000368:Aged; D000450:Aldosterone / Q000097:blood / Q000378:metabolism*; D000804:Angiotensin II / Q000037:antagonists & inhibitors*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use*; D000959:Antihypertensive Agents / Q000494:pharmacology* / Q000627:therapeutic use*; D002908:Chronic Disease; D004359:Drug Therapy, Combination; D015716:Electrocardiography, Ambulatory; D005260:Female; D006333:Heart Failure / Q000188:drug therapy*; D006339:Heart Rate / Q000187:drug effects*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009638:Norepinephrine / Q000097:blood / Q000378:metabolism*; D000077583:Quinapril; D012083:Renin / Q000097:blood / Q000378:metabolism*; D044005:Tetrahydroisoquinolines / Q000494:pharmacology* / Q000627:therapeutic use*; D013777:Tetrazoles / Q000494:pharmacology* / Q000627:therapeutic use*; D014633:Valine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D000068756:Valsartan
D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D044005:Tetrahydroisoquinolines; D013777:Tetrazoles; D000804:Angiotensin II; D000450:Aldosterone; D000068756:Valsartan; D012083:Renin; D014633:Valine; D000077583:Quinapril; D009638:Norepinephrine