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Dual Action Drug Fights Heart Failure

Date:
July 30, 2002
Source:
American Heart Association
Summary:
A dual-action drug, called omapatrilat, was found to be as good as a standard ACE-inhibitor in reducing the risk of death and hospitalization from heart failure, according to a report in Circulation: Journal of the American Heart Association.

DALLAS, July 30 – A dual-action drug, called omapatrilat, was found to be as good as a standard ACE-inhibitor in reducing the risk of death and hospitalization from heart failure, according to a report in today's rapid track Circulation: Journal of the American Heart Association.

"The trial shows that omapatrilat is effective in treating heart failure," says lead researcher Milton Packer, M.D., of Columbia University College of Physicians and Surgeons. "And we have some indications that omapatrilat may be superior to a standard ACE inhibitor in some individuals. Our data suggests that this drug may have a special role in treating people who have both high blood pressure and heart failure."

Researchers analyzed the effects of the drug omapatrilat, which blocks both angiotensin-converting enzyme (ACE) and neutral endopeptidase (NEP). In people with high blood pressure, omapatrilat was better than ACE inhibitors alone in lowering blood pressure. They hypothesized that the drug could also be better than an ACE inhibitor in patients with heart failure because it not only blocks ACE but also blocks NEP – one of the enzymes responsible for breaking down peptides that benefit heart function. In animal studies, simultaneous inhibition of both ACE and NEP produced greater benefits than did ACE inhibition alone.

The trial [called the Omapatrilat Vs. Enalapril Randomized Trial of Utility in Reducing Events (OVERTURE) trial] compared omapatrilat with enalapril, a standard ACE inhibitor. The trial enrolled 5770 patients with heart failure at 704 institutions in 42 countries. Participants had heart failure for more than two months, had left ventricular ejection fraction of 30 percent or less and had been hospitalized for heart failure within the previous year. They were randomly assigned: 2886 to the omapatrilat group and 2884 to the enalapril group. The average age of each group was about 63 years, and about 80 percent of the two groups were men. Patients were evaluated on an outpatient basis every one to four months for an average of 14.5 months.

In the omapatrilat group, 914 patients died or were hospitalized for heart failure serious enough to require intravenous treatment, compared to 973 of those in the enalapril group. This was a 6 percent difference – a result that showed that omapatrilat was effective but not more effective than enalapril. However, further analysis, using a broader definition of heart failure or focusing on all cardiovascular events, suggested that omapatrilat may have been superior to enalapril. Patients who had both hypertension and heart failure showed the greatest advantage of omapatrilat when compared with enalapril. These findings in the post hoc analysis warrant further study, he says.

Both drugs were well tolerated in the study. Patients in the omapatrilat group were more likely to experience dizziness and low blood pressure, whereas patients in the enalapril group were more likely to experience worsening heart function and worsening renal function. Angioedema, a swelling of the head and neck which can rarely be serious enough to cause breathing difficulties, occurred rarely in both groups and was never serious.

"Angioedema has been an important concern when omapatrilat was tested in patients without heart failure, but fortunately, patients with heart failure seem to be resistant to this potential side effect of the drug. This was a very gratifying finding."

Co-authors of the study include: Robert M. Califf, M.D., Marvin A. Konstam, M.D., Henry Krum, MBBS, Ph.D.; John J. McMurray, M.D.; Jean-Lucien Rouleau, M.D.; and Karl Swedberg, M.D., for the OVERTURE Study Group.

The study was funded by Bristol Myers Squibb.


Story Source:

The above story is based on materials provided by American Heart Association. Note: Materials may be edited for content and length.


Cite This Page:

American Heart Association. "Dual Action Drug Fights Heart Failure." ScienceDaily. ScienceDaily, 30 July 2002. <www.sciencedaily.com/releases/2002/07/020730075713.htm>.
American Heart Association. (2002, July 30). Dual Action Drug Fights Heart Failure. ScienceDaily. Retrieved October 21, 2014 from www.sciencedaily.com/releases/2002/07/020730075713.htm
American Heart Association. "Dual Action Drug Fights Heart Failure." ScienceDaily. www.sciencedaily.com/releases/2002/07/020730075713.htm (accessed October 21, 2014).

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