VASOPEPTIDASE INHIBITION WITH OMAPATRILAT: CARDIAC, RENAL AND ENDOCRINE EFFECTS OF THREE MONTH TREATMENT IN CHRONIC HEART FAILURE
D.R. McClean, H. Ikram*, I.G. Crozier, M. Hume, M. Reynolds, A.M. Richards, M.G. Nicholls.
Cardiology Department, Christchurch Hospital, Christchurch, New Zealand.
Background: Omapatrilat is a combined inhibitor of neutral endopeptidase and angiotensin converting enzyme. The purpose of this study was to evaluate the effects of this drug on clinical status, left ventricular and renal function, and neurohormonal changes in chronic heart failure (CHF).
Methods: The study was a randomised, double blind single-centre study in 41 patients with NYHA Class II-IV EF <40%. Patients were randomised to 2.5, 5, 10, 20 or 40mg once daily. Data for all doses combined and also dose-dependent changes. [2.5mgm(control), 5-10mg (low dose) and 20-40mg (high dose)] are shown. Clinical status assessment, echocardiography and digital applanation tonometry were performed at baseline and after 3 months of chronic therapy.
|
HR |
EF |
SP |
UVol |
UNa |
ANP |
BNP |
EPI |
|
|
B |
71 |
24 |
1797 |
66.0 |
47.8 |
|||
|
3 mths |
67* |
28** |
116** |
2148** |
135** |
65.3 |
39.3** |
101** |
|
Change from B |
2.5mg |
5-10mg |
20-40mg |
|
EF |
-3.4 |
6.73** |
7.41** |
|
s |
29.4 |
-33.5 |
-66.4* |
|
SP |
-3.6 |
-16.8 |
-25** |
|
UNa |
12.1 |
14.1 |
47.2 |
Patient clinical assessment of heart failure status at 3 months improved ** (dose-dependent**); B = Baseline; s = meriodional wall stress (g/cm2); SP = systolic pressure (mmHg); UVol = urinary volume (mls/24hr); UNa = urinary sodium (mmol/24hr); EPI = epinephrine (pmol/l); p<05*, p<01**.
Conclusion: Long-term omapatrilat treatment in CHF resulted in a dose-dependent improvement in clinical status and ejection fraction. This is due to dose-related reductions in afterload and blood pressure, with natriuresis, diuresis and improved neuroendocrine status.
