Nesiritide Administered Peri-Anesthesia in Patients Undergoing Cardiac Surgery - NAPA


The goal of the trial was to evaluate the effect of treatment with nesiritide compared with placebo on renal function among patients with left ventricular dysfunction undergoing coronary artery bypass grafting (CABG).

Study Design

Study Design:

Patients Enrolled: 303
Mean Follow Up: 180 days
Mean Patient Age: Mean age 64 years
Female: 22
Mean Ejection Fraction: Mean at baseline 29.9%

Patient Populations:

CABG with cardiopulmonary bypass, with or without mitral valve replacement/repair; age ≥18 years; New York Heart Association class II to IV heart failure; and documented left ventricular ejection fraction ≤40% within 90 days


Aortic valve repair or replacement; requirement for ongoing or chronic dialysis; presence of restrictive or obstructive cardiomyopathy, pericarditis, or pericardial tamponade; documented low cardiac filling pressures; known congenital heart disease; evidence of ongoing infection; and pulmonary disease, including chronic obstructive pulmonary disease or asthma, requiring hospital stay within 60 days

Drug/Procedures Used:

Patients were randomized in a double-blind manner to nesiritide (0.01 µg/kg/min without bolus; n = 141) or placebo (n = 138) started after anesthesia but before chest incision, and to continue for 24-96 hours. All other perioperative and postoperative usual care was to be continued.

Concomitant Medications:

Angiotensin-converting enzyme inhibitors (76%), angiotensin II receptor blockers (8%), beta-blockers (96%), and loop diuretics (68%)

Principal Findings:

Baseline characteristics were well-matched between treatment groups, with New York Heart Association class III in 41% and class IV in 10%. Mean serum creatinine was 1.1 mg/dl. CABG alone was performed in 68% of patients and concomitant mitral valve repair/replacement was performed in 19%. Study drug infusion was administered for a mean of 40 hours and a median of 30 hours.

Mean peak increase in serum creatinine was lower in the nesiritide group compared with placebo (0.15 mg/dl vs. 0.34 mg/dl; p < 0.001), as was the reduction in glomerular filtration rate (-10.8 ml/min/1.73 m2 vs. -17.2 ml/min/1.73 m2; p < 0.001). Among patients with renal dysfunction preoperatively, serum creatinine increased by 3% in the nesiritide group versus 29% in the placebo group. Urine output in the first 24 hours after surgery was higher in the nesiritide group (2926 ml vs. 2350 ml; p < 0.001). Length of hospitalization was shorter in the nesiritide group (mean 9.1 days vs. 11.5 days, p = 0.043); there was no difference in intensive care unit length of stay (78.8 hours vs. 103.2 hours, p = 0.37). Mortality at 180 days was lower in the nesiritide group (6.6% vs. 14.7%, p = 0.046). Serious adverse events did not differ between groups (30.5% for nesiritide vs. 37.0% for placebo).


Among patients with left ventricular dysfunction undergoing CABG surgery with cardiopulmonary bypass, perioperative infusion of nesiritide was associated with improvements in renal function and a reduction in death at 6 months compared with placebo.

Results of the present study were favorable for nesiritide for several endpoints of renal function and a significant reduction in mortality without an increase in adverse events. The benefit was particularly evident in patients with preoperative renal dysfunction. Renal dysfunction is associated with increased mortality and places CABG patients at particularly high risk for postoperative mortality. It should be noted, however, that while the study had many strengths (randomized, double-blind, multicenter, and placebo controlled), the overall sample size was relatively small and the authors described the study as exploratory. Results of the present study differ from studies performed in patients undergoing medical therapy for heart failure, which did not show a beneficial effect of nesiritide on serum creatinine.


Mentzer RM Jr, Oz MC, Sladen RN, et al. Effects of Perioperative Nesiritide in Patients With Left Ventricular Dysfunction Undergoing Cardiac Surgery: The NAPA Trial. J Am Coll Cardiol 2007;49:716-26.

Clinical Topics: Cardiac Surgery, Heart Failure and Cardiomyopathies, Invasive Cardiovascular Angiography and Intervention, Cardiac Surgery and Heart Failure, Acute Heart Failure, Heart Failure and Cardiac Biomarkers

Keywords: Intensive Care Units, Kidney Function Tests, Coronary Disease, Creatinine, Length of Stay, Heart Failure, Stroke Volume, Glomerular Filtration Rate, Cardiopulmonary Bypass, Coronary Artery Bypass, Ventricular Dysfunction, Left, Mitral Valve, Natriuretic Peptide, Brain

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