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CLINICAL STUDIES

The clinical, cardiac, renal, arterial and neurohormonal effects of omapatrilat, a vasopeptidase inhibitor, in patients with chronic heart failure

^a Department of Cardiology, Christchurch Hospital, Christchurch, New Zealand

Manuscript received July 21, 1999; revised manuscript received January 28, 2000, accepted March 30, 2000.

Reprint requests and correspondence: Prof. Hamid Ikram, Department of Cardiology, Christchurch Hospital, Private Bag 4710, Christchurch, New Zealand t.nz
HAMIDI{at}chhlth.gov

OBJECTIVES

We sought to examine the effects of long-term vasopeptidase inhibition in patients with heart failure.

BACKGROUND

The long-term effects of omapatrilat, an agent that inhibits both neutral endopeptidase and angiotensin-converting enzyme, on clinical status, neurohormonal indexes and left ventricular function in patients with chronic heart failure (CHF) have not been previously documented.

METHODS

Forty-eight patients in New York Heart Association functional class II or III, with left ventricular ejection fraction (LVEF) 40% and in sinus rhythm were randomized to a dose-ranging pilot study of omapatrilat for 12 weeks. Measurements were performed at baseline and 12 weeks.

RESULTS

There was an improvement in functional status, as reported by the patient (p < 0.001) and physician (p < 0.001) at 12 weeks. Dose-dependent improvements in LVEF (p < 0.001) and LV end-systolic wall stress (sigma) (p < 0.05) were seen, together with a reduction in systolic blood pressure (p < 0.05). There was evidence of a natriuretic effect (p < 0.001), and total blood volume decreased (p < 0.05). Omapatrilat induced an increase in postdose plasma atrial natriuretic peptide levels (p < 0.01) in the high dose groups, with a reduction in predose plasma brain natriuretic peptide (p < 0.001) and epinephrine (p < 0.01) levels after 12 weeks of therapy. Omapatrilat was well tolerated.

CONCLUSIONS

The sustained hemodynamic, neurohumoral and renal effects of omapatrilat, together with improved functional status, suggest that vasopeptidase inhibition has potential as a new therapeutic modality for the treatment of CHF.

Abbreviations and Acronyms   ACE = angiotensin-converting enzyme   ANP = atrial natriuretic peptide   BNP = brain natriuretic peptide   cGMP = cyclic 3',5'-guanosine monophosphate   CHF = chronic heart failure   LVEF = left ventricular ejection fraction   NEP = neutral endopeptidase   NYHA = New York Heart Association   RAS = renin–angiotensin system

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