Source: Cancer  |  Posted 9 years ago

C-terminal atrial natriuretic peptide (C-ANP) is potentiated more by omapatrilat than lisinopril, even at trough levels, say Canadian, United States and Norwegian researchers.

They identified potentially important effects of omapatrilat on endothelin-1 and anti-inflammatory cytokines in patients with chronic heart failure.

Differences in clinical outcome might be explained by these findings, suggest investigators at the University of Toronto and University Health Network, St. Michael's Hospital, Ontario; Universite de Montreal, Quebec, Canada; Bristol-Myers Squibb, New Jersey; Brigham and Women's Hospital, Boston, United States; and University of Oslo, Norway.

They point out that the effects of angiotensin-converting enzyme (ACE) inhibitors modulate the neurohumoral milieu.

In patients with congestive heart failure, natriuretic peptides, bradykinin, and possibly endothelin-1 may be increased by asopeptidase inhibitors (VPI) which are ACE and neutral endopeptidase inhibitors.

One hundred and seven subjects with ischemic or dilated cardiomyopathy, New York Heart Association functional class II to III, with left ventricular ejection fraction of less than 40 percent were included in this study.

All were receiving treatment with ACE inhibitors and were randomly assigned to two groups for either the VPI omapatrilat 40 mg/day or the ACE inhibitor lisinopril 20 mg/day.

Assessments were made of trough levels of neurohormones (24 hours after dosing) at baseline and at 12 and 24 weeks of follow-up.

C-ANP levels were found to decrease with lisinopril (p = 0.035), though not with omapatrilat.

No change was seen, however, in N-terminal ANP levels.

Both groups showed a tendency for a similar decrease in brain natriuretic peptide (BNP) levels. Both had increased endothelin-1 levels, which was statistically significant with omapatrilat (p = 0.008).

While a decrease was seen in levels of the proinflammatory cytokine interleukin-6, there was an increase in both groups of the anti-inflammatory cytokine interleukin-10. The only statistical significance for interleukin-10, however, was shown with omapatrilat therapy. Catecholamines or angiotensin II were unchanged by either agent.