Therapeutic potential of nesiritide (recombinant b-type natriuretic peptide) in the treatment of heart failure

Abstract

This review outlines the chemical properties, pharmacology and clinical trials data which support the development of nesiritide (synthetic human B-type natriuretic peptide, or hBNP) as a therapeutic agent for patients with decompensated congestive heart failure. Nesiritide is a 32-amino acid peptide, structurally identical to endogenous hBNP. Clinical trials with single bolus, repeated boluses and sustained infusions of nesiritide have demonstrated prompt, significant and sustained reductions in pulmonary capillary wedge pressure and increases in cardiac output, consistent with a direct vasodilator effect. Nesiritide has a short half-life, approximately 18 min, which is not dependent upon renal function. It not associated with tachyphylaxis through 24 h of therapy. Nesiritide is not an inotrope, and its action is not dependent upon beta adrenergic receptors. The safety profile has been excellent; the major adverse effect is hypotension. The frequency of ventricular arrhythmia is not increased in patients treated with nesiritide. In our opinion, nesiritide has many attributes of an ideal first-line therapeutic agent for decompensated heart failure.

Comprehensive Review of the Relative Clinical Utility of B-Type Natriuretic Peptide and N-Terminal Pro-B-Type Natriuretic Peptide Assays in Cardiovascular Disease

“…Recombinant BNP itself (nesiritide or Natricor) is used therapeutically in HF patient to ameliorate acute symptoms such as dyspnea and reduced cardiac output [117,118]. Treatment with these recombinant forms of BNP results in an inhibition of the renin-angiotensin system and aldosterone release, which promotes diuretic and vasodilatory effects.…”

“…It has been shown that NTproBNP does not respond dynamically over the course of a nesiritide infusion, probably because of its longer half-life [119]. Nesiritide has an extremely short half-life of 18 minutes [118]. Thus, although it has been argued that NTproBNP may be advantageous because nesiritide may obscure BNP levels, it is unlikely due to the half-life of the treatment.…”

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

“…Nesiritide (hBNP) represents a new class of drugs with vasodilating properties; it has no inotropic properties, does not inhibit the phosphodiesterase pathway, is not associated with increased cyclic adenosine monophosphate, and works independently of ß-adrenergic receptors [20,21]. Several studies have shown that an infusion of nesiritide, with a half-life of approximately 18 min [21], is associated with decreased pulmonary capillary wedge pressure (PCWP), sys-temic vascular resistance (SVR), and pulmonary artery pressure (PAP), as well as increased cardiac index (CI), stroke volume index (SVI), and natriuresis [12,20]. Nesiritide has demonstrated some potential for decreasing plasma aldosterone [22] without activating the sympathetic system [23].…”

“…Initial trials involving nesiritide utilized bolus doses [20,21,31] or continuous infusions [12,[32][33][34]. The bolus studies utilized sequentially increasing doses in 27 patients [20], repetitive boluses of the same dose in 29 patients [31], and repetitive doses comparing 60 patients with and without ACE inhibitors [21].…”

“…The bolus studies utilized sequentially increasing doses in 27 patients [20], repetitive boluses of the same dose in 29 patients [31], and repetitive doses comparing 60 patients with and without ACE inhibitors [21]. In two continuous infusion studies conducted in Japan, a 0.1-Ìg/kg/min infusion [12,32] was utilized.…”