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).
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.
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.
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.
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
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.
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.