Comparison of the effects of omapatrilat and lisinopril on circulating neurohormones and cytokines in patients with chronic heart failure.
Angiotensin-converting enzyme (ACE) inhibitors exert their effects by modulating the neurohumoral milieu. Vasopeptidase inhibitors (VPI) are ACE and neutral endopeptidase inhibitors and may increase natriuretic peptides, bradykinin, and perhaps endothelin-1 in patients with congestive heart failure. Patients (n = 107) with ischemic or dilated cardiomyopathy, New York Heart Association functional class II to III, with left ventricular ejection fraction <40%, and on ACE inhibitor therapy were randomized to either the VPI omapatrilat 40 mg/day or the ACE inhibitor lisinopril 20 mg/day. Trough levels of neurohormones (24 hours after dosing) were assessed at baseline, and at 12 and 24 weeks of follow-up. C-terminal atrial natriuretic peptide (C-ANP) levels decreased with lisinopril (p = 0.035), but not with omapatrilat. In contrast, N-terminal ANP levels did not change, and brain natriuretic peptide (BNP) levels tended to decrease similarly in both groups. Endothelin-1 levels increased in both groups, the increase reaching statistical significance with omapatrilat (p = 0.008). Levels of the proinflammatory cytokine interleukin-6 tended to decrease, and the anti-inflammatory cytokine interleukin-10 increased in both groups, with statistical significance only for interleukin-10 with omapatrilat therapy. Neither agent changed catecholamines or angiotensin II. Thus, even at trough levels, omapatrilat potentiates C-ANP more than lisinopril. Potentially important effects of omapatrilat on endothelin-1 and anti-inflammatory cytokines were identified, providing potential explanations for differences in clinical outcome.
Sheth
Tej
T
Division of Cardiology, University of Toronto and University Health Network, Toronto, Ontario, Canada.
Parker
Tom
T
Block
Alan
A
Hall
Christian
C
Adam
Albert
A
Pfeffer
Mark A
MA
Stewart
Duncan J
DJ
Qian
Chunlin
C
Rouleau
Jean L
JL
D000368:Aged; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D009320:Atrial Natriuretic Factor / Q000097:blood / Q000187:drug effects; D015415:Biomarkers / Q000097:blood; D002908:Chronic Disease; D016207:Cytokines / Q000097:blood* / Q000187:drug effects*; D004311:Double-Blind Method; D019332:Endothelin-1 / Q000097:blood / Q000187:drug effects; D005260:Female; D005500:Follow-Up Studies; D006333:Heart Failure / Q000097:blood* / Q000188:drug therapy*; D006801:Humans; D017706:Lisinopril / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D020097:Natriuretic Peptide, Brain / Q000097:blood / Q000187:drug effects; D018377:Neurotransmitter Agents / Q000097:blood*; D011237:Predictive Value of Tests; D011446:Prospective Studies; D011725:Pyridines / Q000627:therapeutic use*; D013318:Stroke Volume / Q000187:drug effects / Q000502:physiology; D013841:Thiazepines / Q000627:therapeutic use*; D016896:Treatment Outcome
D000806:Angiotensin-Converting Enzyme Inhibitors; D015415:Biomarkers; D016207:Cytokines; D019332:Endothelin-1; D018377:Neurotransmitter Agents; D011725:Pyridines; D013841:Thiazepines; D020097:Natriuretic Peptide, Brain; C106266:omapatrilat; D009320:Atrial Natriuretic Factor; D017706:Lisinopril