Nesirtide, Safety and Efficacy: A Review

摘要

Nesiritide, a recombinant form of human B-type natriuretic peptide is the first new parenteral agent to gain approval from FDA for acute decompensated heart failure in more than a decade. Although Nesiritide has been well studied in many trials and has been shown to be safe and effective, a recent meta-analysis report of increased 30 day mortality and worsening of renal function has created controversies with the use of nesiritide. The problems intrinsic to these meta-analyses were a heterogeneous patient population, enrolled in randomized controlled fashion and none of these trials were designed or powered to assess mortality risk. Until additional therapeutic trials are conducted, use of nesiritide should be based on clinical and hemodynamic improvement but at the same time it is imperative to use nesiritide only at approved doses and for approved duration which might minimize the risk of increased mortality and renal impairment. Introduction Congestive Heart Failure (CHF) is a health care problem of enormous proportions with a dramatic economic impact costing about $10 billion annually with $5,501 spent for every hospital-discharge diagnosis of heart failure 1 . CHF is one of the most expensive conditions covered by medicare. Although there has been a remarkable improvement in our understanding and treatment of chronic heart failure in the past few years with availability of new drugs coupled with progress in cardiac transplantation, little if any advance has been made in the management of acute decompensated heart failure (ADHF). Admissions to the hospital for decompensation are a frequent occurrence and inpatient management of these patients is a major health burden. This is exemplified by the fact that in 1999, heart failure was the primary discharge diagnosis in 962,000 hospitalized patients, representing a 150% increase since 1979 2 . About 5 million people in the United States have heart failure and each year 550,000 new patients are diagnosed with heart failure, the incidence of the disease being approximately 10 per 1000 Americans over the age of 65. In the foreseeable future, admissions to hospital for acute decompensated heart failure is likely to continue to increase 3,4 .Symptomatic decompensation is the most common reason for hospitalization of patients with CHF. About 21% of patients who come to the emergency room (ER) with ADHF are experiencing their first episode and 79% have had prior hospital visits for the same condition. The management of ADHF in the emergency medical setting poses a major clinical challenge with in-hospital mortality rate for ADHF being 5-8%. Therefore, rapid application of effective intervention is desirable to achieve clinical stability. Hospital management of ADHF has changed little over the last several years with standard therapy directed toward rapid relief of symptoms utilizing parenteral medications to mobilize fluid and improve hemodynamic function. Initial regimen usually includes intravenous diuretics, vasodilators (nitroglycerine, nitroprusside), and /or positive inotropes (dobutamine, milrinone) to decrease cardiac filling pressures and increase cardiac output 4,5,6,7,8 .Nesiritide, Natriuretic Peptides and Heart FailureNesiritide is recombinant human B-type natriuretic peptide (BNP), derived from E.coli using recombinant DNA technology. BNP is a 32 amino acid peptide with vasodilating, natriuretic, and diuretic properties, originally isolated from porcine brain and subsequently found to be produced in humans in the heart, primarily by the left ventricle. Plasma concentrations of BNP are increased in patients with chronic CHF and correlate well with several clinical and hemodynamic parameters of disease severity 3,4,5,6 . BNP belongs to the family of natriuretic peptides, which play a role in cardiorenal homeostasis. There are at least four members in this family (Table 1) viz; hANP (human atrial natriuretic peptide), hBNP (human brain natriuretic peptide), CNP (C-type natr