Omapatrilat Reduces Pulse Pressure Better Than Enalapril

Laurie Barclay, MD

June 04, 2002

June 5, 2002 -- Omapatrilat, a combination angiotensin-converting enzyme (ACE) and vasopeptidase inhibitor, reduces arterial stiffness and consequently pulse pressure better than the ACE-inhibitor enalapril, according to results of a study published in the June 25 issue of Circulation, a journal of the American Heart Association (the article was published online May 28). This class of agent may prove to be a valuable addition to existing hypertensive management.

"Up to this time, we've only had limited understanding of how various blood pressure lowering drugs affect arterial stiffness," lead author Gary F. Mitchell, MD, from Cardiovascular Engineering, Inc., in Holliston, Massachusetts, says in a news release. "Large artery stiffening was thought to be a natural irreversible part of aging. This study clearly demonstrates that the stiffness in large arteries can be reduced and that the reduction in stiffness is beyond what would be seen using drugs that lower blood pressure by other mechanisms."

While ACE inhibitors reduce levels of vasoconstrictors, vasopeptidase inhibitors reduce vasoconstrictor levels and increase vasodilators. In the 12-week, double-blind Conduit Hemodynamics of Omapatrilat International Research Study (CHOIRS), 167 patients with moderate systolic hypertension were randomized to treatment with enalapril 40 mg or omapatrilat 80 mg daily.

"We thought [omapatrilat] was going to be a magic combination in terms of vessel stiffness and it is exactly as we had hypothesized," Mitchell says.

Omapatrilat reduced peripheral pulse pressures by 8.2 mm Hg, compared with 4.0 mm Hg for enalapril ( P < 0.05). Central pulse pressure dropped 10.2 mm Hg with omapatrilat and 3.2 mm Hg with enalapril ( P < 0.01). These reductions in pulse pressure were attributable to a reduction in central aortic stiffness. Adverse effects were similar in both groups.

"Because the effects of omapatrilat on vessel function were in excess of those achieved by the ACE inhibitor, the mechanism of action of omapatrilat may be responsible for these results," says Marc A. Pfeffer, MD, PhD, director of the clinical coordinating center for CHOIRS. "The impact of these unique properties on large vessels needs to be further studied to determine if they will translate into improved clinical outcomes."

Bristol-Myers Squibb funded this study and provided research grants, honoraria, and/or employment to the authors.

Circulation. 2002;105:000-000 [ Abstract]

Reviewed by Gary D. Vogin, MD