Effects of Perioperative Nesiritide in Patients With Left Ventricular Dysfunction Undergoing Cardiac Surgery. The NAPA Trial

Abstract

Objectives: The purpose of this study was to determine the role nesiritide might play in patients with left ventricular dysfunction undergoing coronary artery bypass grafting (CABG) using cardiopulmonary bypass (CPB). Background: Given the hemodynamic, neurohormonal, and renal effects of natriuretic peptides, nesiritide might be useful in the management of patients undergoing cardiac surgery. Methods: This prospective, double-blind, exploratory evaluation randomly assigned patients with ejection fraction ≤40% who were undergoing CABG with anticipated use of CPB to receive either nesiritide or placebo, in addition to usual care, for 24 to 96 h after induction of anesthesia. Postoperative renal function, hemodynamics, and drug use (primary end points) were assessed in patients who underwent CABG using CPB; mortality and safety (secondary end points) were assessed in all patients who received the study drug. Results: Of 303 randomized patients, 279 received the study drug and 272 underwent CABG using CPB. Compared with placebo, nesiritide was associated with a significantly attenuated peak increase in serum creatinine (0.15 ± 0.29 mg/dl vs. 0.34 ± 0.48 mg/dl; p < 0.001) and a smaller fall in glomerular filtration rate (-10.8 ± 19.3 ml/min/1.73 m2 vs. -17.2 ± 21.9 ml/min/1.73 m2; p = 0.001) during hospital stay or by study day 14, and a greater urine output (2,926 ± 1,179 ml vs. 2,350 ± 1,066 ml; p < 0.001) during the initial 24 h after surgery. In addition, nesiritide-treated patients had a shorter hospital stay (p = 0.043) and lower 180-day mortality (p = 0.046). Conclusions: Nesiritide in the setting of CABG with CPB is associated with improved postoperative renal function and possibly enhanced survival. (The NAPA Trial; http://www.clinicaltrials.gov/ct/show; NCT00090792). © 2007 American College of Cardiology Foundation.