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University of Cincinnati Academic Health Center
Publish Date: 03/08/99
Media Contact: AHC Public Relations, (513) 558-4553
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Nesiritide Improves Symptoms and Hemodynamics in Acute Congestive Heart Failure (CHF) Patients Regardless of Disease Severity

New Orleans, Louisiana—At a scientific session today held at the annual meeting of the American College of Cardiology (ACC), researchers from the University of Cincinnati Medical Center presented findings showing that the investigational drug nesiritide (Natrecor®) rapidly improved symptoms and produced dose-related improvement in hemodynamic parameters in both moderate and severe patients suffering from acutely decompensated congestive heart failure (CHF).

"Nesiritide produced significant improvements in patients who had a history of either moderate or severe CHF, indicating that it is effective regardless of disease severity," said William Abraham, M.D., lead author of the study and director, Section of Heart Failure and Cardiac Transplantation, as well as associate professor of medicine for the Division of Cardiology, University of Cincinnati Medical Center. "While past studies have demonstrated that nesiritide produces improvements in acutely decompensated CHF patients, this was the first to directly compare patients differing in their history of CHF severity broadening the therapeutic benefit it would offer."

In the study, 124 hospitalized patients with a history of either moderate or severe CHF received one of two dosing levels of nesiritide (0.015 or 0.030 mcg/kg/min) or a placebo. At baseline and after six hours of therapy, the researchers measured global symptoms, shortness of breath, and two key hemodynamic parameters: pulmonary capillary wedge pressure (PCWP), a measure of the pressure in the heart that, when elevated, forces fluid into the lungs, causing respiratory problems; and cardiac index (CI), a measure of how much blood the heart is circulating.

At both dosage levels, nesiritide significantly improved symptoms and hemodynamics in the moderate and severe CHF patients. For example, among moderate CHF patients, those receiving 0.015 mcg/kg/min nesiritide showed improvements vs. placebo patients in global symptoms (68% vs. 20%), shortness of breath (68% vs. 12%), PCWP (-25% vs. 2%), and CI (14% vs. 1%). Similar improvements at the 0.015 dosage level vs. placebo were seen in severe CHF patients global symptoms (50% vs. 7%), shortness of breath (44% vs. 13%), PCWP (-15% vs. 20%), and CI (19% vs. -6%).

Additionally, the study showed that there was a dose-related hemodynamic improvement after infusion of nesiritide. These results were found in both the moderate patients in whom CI increased (14% vs. 32%) and PCWP decreased (-25% vs. -33%), and the severe patients in whom CI increased (19% vs. 27%) and PCWP decreased (-15% vs. -36%).

Nesiritide is the genetically engineered form of the naturally occurring human cardiac hormone, human b-type natriuretic peptide (hBNP), which is secreted as part of the body's natural response to a failing heart. In many acute CHF patients, the body's response isn't enough to reverse the debilitating symptoms of CHF. Nesiritide functions as a balanced vasodilator, reducing the pressure in blood vessels going to and from the heart, allowing the heart to circulate blood more efficiently. In effect, nesiritide augments the body's natural physiologic response to CHF.

Previous controlled studies indicate that infusion of nesiritide also promotes mild diuresis (fluid excretion) by acting on the kidneys and decreasing levels of aldosterone, a neurohormone that promotes fluid and sodium retention. Nesiritide generally has been well tolerated when administered to patients with decompensated CHF. The most common side effect of nesiritide was a dose-related decrease in blood pressure, an extension of the desired pharmacologic effect, and one that is easily monitored and treated in the hospital setting. The incidence of symptomatic hypotension with nesiritide was not significantly different from placebo.

CHF affects about five million people in the U.S. and 15 million worldwide. A potentially life-threatening disease that has no cure, CHF is a chronic condition in which the heart functions inefficiently and circulation is reduced to the body's organs. As a result, fluid accumulates in the tissues, including the lung tissue, resulting in symptoms such as severe shortness of breath, peripheral edema, fatigue, dry cough, difficulty sleeping, and/or weight gain. CHF may result from an acute event (e.g., heart attack) or may develop gradually over time as a result of coronary artery disease, hypertension, abnormal heart valves or other heart-related causes.

Nearly all CHF patients suffer at least one acute episode in which symptoms become so pronounced that hospital treatment is required to stabilize their condition. A sudden increase in dietary sodium, failure to take medications for managing CHF or the development of a new heart arrhythmia can precipitate an acute attack. Acute CHF is the primary diagnosis in approximately one million patients hospitalized in the U.S. each year, and is a secondary diagnosis in an additional two million. In the U.S., CHF accounts for the largest cause of hospitalizations for patients over age 65.

Current treatment of CHF includes diuretics to remove excess fluid from the body, vasodilators to improve blood flow to the body, and inotropic agents to increase the heart's pumping action.

Nesiritide was developed by Scios Inc., a biopharmaceutical company located in Mountain View, California. In April 1998, Scios submitted a new drug application (NDA) for nesiritide to the United States Food and Drug Administration for the treatment of acute CHF. In May 1998, Bayer AG of Leverkusen, Germany formed an alliance with Scios for the worldwide commercialization of nesiritide once regulatory approvals are obtained.



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