Natriuretic and Neurohormonal Responses to Nesiritide, Furosemide, and Combined Nesiritide and Furosemide in Patients With Stable Systolic Dysfunction

BACKGROUND: In patients with heart failure, few data describe the neurohormonal response to nesiritide and furosemide either alone or in combination. This study systematically compared the effects of nesiritide, furosemide, and their combination on natriuresis/diuresis and plasma aldosterone in patients with chronic stable heart failure who were relatively diuretic resistant. HYPOTHESIS: Natriuretic, diuretic, and neurohormonal responses to furosemide and nesiritide will differ when these agents are administered alone vs. in combination. METHODS: Twenty-eight subjects completed a multicenter, open-label, three-arm crossover study. Each subject received the following treatments in random order on alternate days: (1) furosemide, 40 mg intravenous bolus; (2) nesiritide, 2 microg/kg intravenous bolus followed by a 0.01 microg/kg/min infusion for 6 hours; (3) both furosemide and nesiritide, with furosemide given at least 15 minutes after initiation of nesiritide. RESULTS: Plasma aldosterone increased by 2.2 +/- 1.6 ng/dL after furosemide alone, decreased by 3.9 +/- 1.6 ng/dL after nesiritide alone (P = 0.005 vs furosemide alone and P = 0.56 vs furosemide plus nesiritide), and decreased by 2.8 +/- 1.6 ng/dL after furosemide plus nesiritide (P = 0.02 vs furosemide alone). CONCLUSIONS: Furosemide alone produced natriuresis/diuresis and a prompt rise in plasma aldosterone values. Nesiritide alone produced no significant natriuresis/diuresis, but decreased plasma aldosterone values. When furosemide was administered on a background of nesiritide infusion, the observed natriuresis/diuresis was similar to that seen with furosemide alone, without the anticipated increase in plasma aldosterone observed with furosemide alone.