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Effects of the vasopeptidase inhibitor, omapatrilat, in 723 patients with coronary heart disease

Bruce Neal

Institute for International Health, 144 Burren Street, PO Box 576, Newtown, NSW 2042, Australia, bneal{at}iih.usyd.edu.au

Introduction

Among individuals with a history of myocardial infarction (MI), higher levels of blood pressure (BP) are associated with increased long-term risks of death from coronary heart disease. Treatment with a BPlowering regimen, based on omapatrilat may result in greater clinical benefits than treatment with a regimen based on a regular angiotensin-converting enzyme (ACE) inhibitor because of more favourable effects on the renin-angiotensin-aldosterone system.

Methods

Seven hundred and twenty-three clinically stable patients with a history of MI or unstable angina, and a mean entry BP of 134/77 mmHg, were randomised to six months treatment with omapatrilat 40 mg, omapatrilat 20 mg, or matching placebo.

Results

After six months, mean BP levels (systolic/diastolic) in the omapatrilat 40 mg group were reduced by 4.3/ 2.9 mmHg (95% confidence interval 1.3 to 7.2/1.2 to 4.6). Mean BP levels in the omapatrilat 20 mg group were reduced by 4.6/1.0 mmHg (1.6 to 7.6/—0.7 to 2.6) in comparison with the placebo group. Both doses of omapatrilat also produced significant decreases in plasma ACE activity and significant increases in levels of plasma renin activity, atrial natriuretic peptide, endothelin and homocysteine (p<0.05 for all). Premature discontinuations were more frequent with omapatrilat than with placebo (p<0.001 for 20 mg and 40 mg).

Conclusions

Omapatrilat produced changes in BP, neurohormone and biochemical parameters that were similar for the two doses. The long-term clinical implications of the observed effects are uncertain and a large-scale randomised trial would be required to reliably establish the effects of omapatrilat on the risks of major vascular disease events among patients with coronary heart disease.

Key Words: blood pressure • drugs • trials • hormones • coronary disease

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Journal of Renin-Angiotensin-Aldosterone System, Vol. 3, No. 4, 270-276 (2002)
DOI: 10.3317/jraas.2002.049


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This Article Abstract Free Full Text (Free PDF) Free Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to Saved Citations Download to citation manager Request Permissions Request Reprints Add to My Marked Citations Citing Articles Citing Articles via Google Scholar Citing Articles via Scopus Google Scholar Articles by Neal, B. Search for Related Content PubMed PubMed Citation Articles by Neal, B. Social Bookmarking                         What's this?