American Heart Association: Nesiritide Reduces Mortality Risk in Heart Failure

14 Apr

Heart FailureSpeaker: Uri Elkayam, MD, Professor, and Director, Heart Failure Program, Los Angeles County University of Southern California Medical Center, Los Angeles, California

Nesiritide (Natrecor, Scios), a recombinant form of human B-type natriuretic peptide (BNP), may diminish the increased acute mortality risk associated with worsening renal function in patients with chronic decompensated heart failure.

Even though nesiritide has been linked to an increased risk of serum creatinine elevations in some patients, the actual effect of nesiritide-associated serum creatinine increases on mortality is unknown.
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Pooled data were analyzed from five randomized trials that evaluated the efficacy and safety of nesiritide in 1,248 patients with chronic decompensated heart failure. Mortality was assessed at 30 days in patients whose serum creatinine increases were more than 0.5 mg/dl within 30 days. The hazard ratios associated with these increases were compared in the patients treated with nesiritide and the controls. Patients in the control group were given standard therapy, including inotropes, nitroglycerin, and/or diuretics.

In total, 214 of the 1,248 patients in the pooled study showed serum creatinine increases greater than 0.5 mg/dl—151 of 768 in the nesiritide group (19%) and 63 of 462 in the control group (14%). A serum creatinine increase of greater than 0.5 mg/dl was associated with a 1.1-fold increase in 30-day mortality risk in the patients receiving nesiritide and a 3.4-fold increase in 30-day mortality risk in the controls.

Early Benefits of Levosimendan for Acute Decompensated Heart Failure

Speaker: Alexandre Mebazaa, MD, PhD, Professor, Department of Anesthesiology and Critical Care, Hopital Lariboi-siere, Paris, France

An experimental drug in the U.S., levosimendan (Simdax, Abbott) has the dual action of calcium sensitization and potassium adenosine triphosphatase channel opening. When given together with standard therapy, levosimendan showed early benefits in reducing the important heart disease marker B-type natriuretic peptide (BNP). However, the regimen did not meet the overall goal of reducing mortality by 25% in patients with acute decompensated heart failure. BNP was one of several secondary endpoints evaluated.
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Investigators randomly assigned 1,327 patients from nine European countries to receive levosimendan as a 12-mcg/kg bolus, followed by a dose of 0.2 mcg/kg per minute, or dobu-tamine (Dobutrex, Eli Lilly) at 5 mcg/kg per minute, for 24 hours, along with standard therapy. (Dobutamine is commonly used for acute decompensated heart failure, but it is associated with an increased risk of death.) The standard therapy consisted of physician-selected drugs such as diuretics, vasodilators, and inotropes.

The primary endpoint of the study was all-cause mortality during 180 days of follow-up.

There was a clear trend toward all-cause mortality with levosimendan, but the rate was only 15% at 30 days, far short of the study’s goal. However, an important difference was discovered in the activity of levosimendan and dobutamine. Before treatment, BNP levels were equally high in both groups, confirming the presence of heart failure in these patients. After five days of treatment, BNP levels declined by 46% with levosimendan therapy and by only 13% with dobutamine.