New treatment for acute congestive heart failure
The patient presents to the emergency room gasping for air; his hands and feet are grotesquely swollen. The diagnosis: acutely decompensated congestive heart failure (ADCHF). Some five million Americans have heart failure and acute CHF accounts for approximately one million hospital admissions each year.
Typically, patients can be stabilized with the use of intravenous diuretics, vasodilators, and positive inotropic agents to decrease cardiac filling pressures and increase cardiac output. But some of these therapies have drawbacks. Inotropes can increase the incidence of cardiac arrhythmias, while the need to slowly titrate the dosing of nitroglycerin (NTG) may cause delays in attaining positive responses in acutely ill patients. Now physicians will have another therapeutic option to help treat these patients.
The Food & Drug Administration has approved nesiritide (Natrecor, Scios) for the treatment of patients with ADCHF who have dyspnea at rest or with minimal activity. The IV medication is the first new therapy approved for this indication in more than a decade.
Nesiritide is the first of a new class of drugs known as human B-type natriuretic peptides, which are recombinant forms of natural vasodilatory proteins. Based on clinical trials, systemic infusion of nesiritide results in beneficial hemodynamic actions, including arterial and venous dilation, enhanced sodium excretion, and suppression of the renin-angiotensin-aldosterone and sympathetic nervous symptoms.
"The extensive data collected and reported on nearly 1,000 patients treated with Natrecor to date suggest an important role for this drug," said James Young, M.D., a lead investigator and medical director of the Kaufman Center for Heart Failure, Cleveland Clinic Foundation. "Natrecor helps improve breathing and decreases pulmonary capillary wedge pressure (PCWP)the two most important things we can do for these patients," he said.
Two years ago, the FDA unexpectedly rejected an advisory panel's recommendation to approve nesiritide because of concerns that up to 14% of trial patients experienced hypotension. This led Scios to initiate a new trial, Vasodilation in the Management of Acute Congestive heart failure (VMAC), which tested a smaller dose of nesiritide.
The FDA based its approval on data from several controlled clinical trials in patients with acute CHF, including the VMAC study. VMAC participants were randomized and treated with nesiritide, IV NTG, or placebo (for three hours). Nesiritide produced a 20% decrease in PCWP at three hoursmost of it in the first 15 minuteswhich was significantly better than the 7% decrease in PCWP at three hours for the placebo group.
"Ninety-five percent of the three-hour effect on PCWP is seen within one hour of Natrecor infusion," noted Richard Brewer, Scios' president and CEO, during a recent teleconference. "We feel Natrecor should be used as initial therapy along with diuretics for ADCHF patients," he continued. He also noted that nesiritide is the first product to receive FDA approval for ADCHF that shows an improvement in breathing in these patients.
The primary adverse effect seen with nesiritide is hypotension. The incidence of symptomatic hypotension occurred in 4% of patients receiving nesiritide compared with 5% of patients receiving IV NTG in the pivotal trial. However, the duration was longer with nesiritide than with NTG, underscoring the importance of administering nesiritide in a setting where blood pressure can be monitored closely.
According to the package labeling, the dose of nesiritide should be reduced or the drug discontinued in patients who develop symptomatic hypotension. It was noted during the teleconference that most of the incidences of symptomatic hypotension were "mild and easily manageable." However, the FDA cautioned physicians that the side effect may not appear for four to five hours after treatment so patients must be monitored for a longer period of time than with NTG. Asymptomatic hypotension was reported equally (8%) in both nesiritide- and NTG-treated patients .
Nesiritide has not been associated with an increase in the incidence of cardiac arrhythmias and does not appear to interact with other agents used concurrently in the treatment of acute CHF.
Scios has priced nesiritide at $380 per vial, which will typically treat a patient for 24 hours. The average patient in the VMAC trial used two vials.
Tammy Chernin. New heart drug helps patients breathe easier. Drug Topics Sep. 3, 2001;145:12.