Company: Scios
Approval Status: Approved August 2001
Treatment for: Acutely decompensated congestive heart failure
General Information
Natrecor has been approved by the FDA for the
intravenous treatment of subjects with acutely decompensated congestive
heart failure (CHF) who have shortness of breath at rest or with minimal
activity.
Natrecor is a recombinant form of human B-type
natriuretic peptide (hBNP), a naturally occurring hormone secreted by the
ventricles. It is the first of this drug class to be made available as a
therapeutic for human disease in the United States. Scios anticipates
launching the drug in US hospitals by the end of August.
Congestive heart failure is caused by a reduction
in the heart's pumping strength, producing a reduced outflow of blood from
the left side of the heart. During acutely decompensated CHF, the heart's
already compromised ability to circulate blood throughout the body worsens,
causing symptoms to become severe enough to require hospital treatment to
stabilize the subject's condition. Events that can precipitate acutely
decompensated CHF include a sudden increase in dietary sodium and failure to
take chronic oral medications.
Clinical Results
Natrecor has been evaluated in 10 trials that
included 941 subjects with congestive heart failure.
The randomized, double-blind VMAC (Vasodilation in
the Management of Acute Congestive Heart Failure) trial included 489
subjects who required hospitalization for management of shortness of breath
at rest due to acutely decompensated CHF. The trial compared the effects of
Natrecor, placebo and intravenous nitroglycerin when added to background
therapy. Among other measures, the trial was designed to evaluate the change
from baseline in pulmonary capillary wedge pressure (PCWP) and the change
from baseline in subjects' dyspnea (abnormal breathing), evaluated after
three hours.
Results demonstrated that subjects receiving
Natrecor reported greater improvement in their dyspnea at three hours than
subjects receiving placebo. Additionally, there was a greater reduction in
mean PCWP for the Natrecor-treated group compared to placebo- and
nitroglycerin-treated subjects.
In a second double-blind trial, 127 subjects
requiring hospitalization for symptomatic CHF were randomized to receive
placebo or one of two doses of Natrecor. Results demonstrated that subjects
receiving both doses of Natrecor reported greater improvement in dyspnea at
six hours compared to subjects receiving placebo.
Side Effects
Adverse events that occurred during the first 24
hours of Natrecor infusion in clinical trials include (but are not limited
to) the following:
- Hypotension
- Ventricular tachycardia (abnormally fast heart
rate)
- Angina pectoris (chest pain)
- Bradycardia (abnormally slow heart rate)
- Headache
- Abdominal pain
- Back pain
- Insomnia
- Dizziness
- Anxiety
- Nausea
- Vomiting
Mechanism of Action
Human BNP binds to the particulate guanylate
cyclase receptor of vascular smooth muscle and endothelial cells, leading to
increased intracellular concentrations of guanosine 3'5'-cyclic
monophosphate (cGMP) and smooth muscle cell relaxation. Cyclic GMP serves as
a second messenger to dilate veins and arteries. Nesiritide has been shown
to relax isolated human arterial and venous tissue preparations that were
precontracted with either endothelin-1 or the alpha-adrenergic agonist,
phenylephrine.
In human studies, nesiritide produced
dose-dependent reductions in pulmonary capillary wedge pressure (PCWP) and
systemic arterial pressure in subjects with heart failure.
In animals, nesiritide had no effects on cardiac
contractility or on measures of cardiac electrophysiology such as atrial and
ventricular effective refractory times or atrioventricular node conduction.
Naturally occurring atrial natriuretic peptide (ANP),
a related peptide, increases vascular permeability in animals and humans and
may reduce intravascular volume. The effect of nesiritide on vascular
permeability has not been studied. (from Natrecor Prescribing Information)
Additional Information
For additional information on Natrecor, please
visit the Scios
web site.
