Nesiritide: A Promising New Drug for the Treatment of Decompensated Heart Failure

Abstract

Heart failure is characterized by sodium and fluid retention, sympathetic overactivity, parasympathetic withdrawal, vasoconstrictor activation and cytokine elevation. Current treatment for acute heart failure consists of vasodilators, diuretics and inotropes. Nesiritide (human B-type natriuretic peptide) is a promising new class of drugs that has been given to almost 1,000 patients in numerous clinical investigations. The clinical development of nesiritide included dosing studies (utilizing repetitive boluses, continuous infusions, or a combination of bolus plus infusion), pivotal efficacy trials, and comparative safety studies, which have repeatedly demonstrated that intravenous nesiritide decreases pulmonary capillary wedge pressure, systemic vascular resistance, mean right atrial pressure and pulmonary artery pressure, while increasing cardiac index and stroke volume. Improvement in both clinical assessment and signs and symptoms of heart failure has been reported by patient and physician alike. Plasma levels of neurohormones and endothelin-1 are significantly reduced with nesiritide treatment. Compared with dobutamine, nesiritide is not proarrhythmic and does not affect heart rate. In comparison with intravenous nitroglycerin in the treatment of decompensated heart failure, nesiritide improves hemodynamics and symptomatology (dyspnea) faster and more effectively than nitroglycerin. Fewer patients receiving nesiritide reported any adverse event. Incidence of hypotension was comparable, but more intravenous nitroglycerin patients developed headache and abdominal pain. Current research supports an important role for the use of nesiritide in the treatment of decompensated heart failure.

Observation unit treatment of heart failure with nesiritide: Results from the proaction trial

“…Antagonism of the neurohormonal axis may explain the revisit benefits of nesiritide. The use of nesiritide has been demonstrated to lower serum levels of aldosterone and endothelin, and to decrease activation of both the renin-angiotensin and sympathetic nervous systems (19). Therefore, when the neurohormonal antagonist nesiritide is given concurrent with diuresis, reflex augmentation of the renin-angiotensin axis is inhibited.…”

Natriuretic Peptides: Future Use?

“…Natriuretic peptides have been evaluated in a number of smaller trials, and, as reviewed in the paper of Burger and Burger [10] in this issue of Heart Drug, about a thousand patients with decompensated heart failure have to date been treated with human recombinant BNP, which has been given the generic name neseritide. Neseritide has been shown to favour haemodynamics by reducing pulmonary capillary wedge pressure, reducing systemic vascular resistance, right atrial pressure and pulmonary artery pressure and increasing the cardiac index and stroke volume.…”

New Advances in the Synthesis of Emerging Cyclic Amidrazones to Foster Bioisosterism of Azaheterocycles

“…These entities can be regarded as bioisoster of a large range of aza‐heterocyclic ring systems (Figure 1). [6] …”