Effects of omapatrilat on systemic arterial function in patients with chronic heart failure.
The mechanisms of action of omapatrilat, an agent that inhibits both neutral endopeptidase 24.11 and angiotensin-converting enzyme, on arterial function in patients with heart failure have not been previously reported. Forty-eight patients in New York Heart Association functional class II to III, left ventricular ejection fraction < or = 40%, and in sinus rhythm were randomized to a dose-ranging (2.5, 5, 10, 20, or 40 mg) study of omapatrilat for 12 weeks. Measurements were obtained at baseline and 12 weeks. Decreases in systolic (25.0 +/- 4.5 vs 2.8 +/- 5.0 mm Hg, p < 0.05) and mean arterial (13.9 +/- 3.0 vs 0.3 +/- 3.3 mm Hg, p < 0.05) pressure were seen after 12 weeks of therapy with higher doses. Ventricular-arterial coupling was improved with a dose-related decrease in augmentation index (-13.8 +/- 1.7% vs +6.1 +/- 2.1%, p < 0.01). There was no change in resting forearm blood flow between groups; however, maximum forearm vasodilator response during reactive hyperemia increased in the high-dose groups compared with the control group (+266 +/- 43% vs - 14 +/- 92%, p < 0.05). Omapatrilat induced an increase in postdose plasma atrial natriuretic peptide levels (30 +/- 11 vs -2 +/- 7 pmol/L, p < 0.01) in high-dose groups consistent with endopeptidase 24.11 inhibition. Omapatrilat shows beneficial changes in ventricular-vascular coupling and arterial function in heart failure.
McClean
D R
DR
Department of Cardiology, Christchurch Hospital, New Zealand.
Ikram
H
H
Garlick
A H
AH
Crozier
I G
IG
D000368:Aged; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects; D009320:Atrial Natriuretic Factor / Q000097:blood; D001794:Blood Pressure / Q000187:drug effects*; D002908:Chronic Disease; D004305:Dose-Response Relationship, Drug; D005260:Female; D006333:Heart Failure / Q000175:diagnosis / Q000188:drug therapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011725:Pyridines / Q000008:administration & dosage* / Q000009:adverse effects; D013318:Stroke Volume / Q000187:drug effects; D013841:Thiazepines / Q000008:administration & dosage* / Q000009:adverse effects; D014664:Vasodilation / Q000187:drug effects*; D016277:Ventricular Function, Left / Q000187:drug effects
D000806:Angiotensin-Converting Enzyme Inhibitors; D011725:Pyridines; D013841:Thiazepines; C106266:omapatrilat; D009320:Atrial Natriuretic Factor