The Pharmaceutical Journal
Vol 269 No 7209 p151
3 August 2002

This article
Reprint
Photocopy

News summary

Vasopeptidase inhibitor is an effective treatment for chronic heart failure

Omapatrilat, a vasopeptidase inhibitor, is effective in treating heart failure, a new study shows. It reduces all-cause mortality and admission to hospital for chronic heart failure requiring intravenous treatment.

Omapatrilat has a dual mechanism of action and works by inhibiting two enzymes, angiotensin-converting enzyme (ACE) and neutral endopeptidase (NEP).

Dr Milton Packer, College of Physicians and Surgeons, Columbia University, New York, randomly assigned 5,770 patients to receive either omapatrilat, titrated up to 40mg once daily (n=2,886) or enalapril (n=2,884), titrated up to 10mg twice daily. Patients were eligible for the study if they had heart failure because of an ischaemic or non-ischaemic cardiomyopathy for two months or more, or had a left ventricular ejection fraction of 30 per cent or less and had been admitted to hospital for heart failure within the previous 12 months.

The percentage of patients who died or were admitted to hospital for heart failure requiring intravenous treatment was 33.7 per cent in the omapatrilat group and 31.7 per cent in the enalapril group, a result which the authors say showed non-inferiority but not superiority of omapatrilat over enalapril. The number of deaths was 477 in the omapatrilat group and 507 in the enalapril group.

They conclude that omapatrilat reduced the morbidity and mortality of patients with moderate to severe heart failure but was not more effective than ACE inhibition alone in decreasing the risk of death and admission to hospital for heart failure requiring intravenous treatment. However, secondary and post hoc analyses that relied on a broader definition of heart failure or focused on all cardiovascular events suggested the possibility that omapatrilat may be more effective than enalapril in these patients. They add that their inability to demonstrate that omapatrilat is superior to enalapril may have been related to deficiencies in both the effectiveness of NEP inhibition or ACE inhibition achieved by omapatrilat in the dosing regimens used.

The study is published as a rapid track publication on the Circulation website (www.circulationaha.org).

Bristol-Myers Squibb, the company developing the drug for both hypertension and heart failure, withdrew its marketing application for the product in the US in 2000, following questions about the risk of angioedema associated with the drug (PJ, 29 April 2000, p646). The company said that last week, the FDA advisory committee declined an application for omapatrilat for use in hypertension, again because of safety concerns. However, it plans to continue discussions with the FDA and evaluate options for potential use in a high-risk population.

Dr Neal Maskrey, medical director, National Prescribing Centre, told The Journal: "We have been interested in reports of trials of this drug for some time. If licensed it will add to the number of therapeutic options for people with heart failure, but at present it seems that ACE inhibitors and beta-blockers will remain the cornerstones of therapy for most people."