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EXPEDITED REVIEW

Effects of Perioperative Nesiritide in Patients With Left Ventricular Dysfunction Undergoing Cardiac Surgery

The NAPA Trial

Robert M. Mentzer, Jr, MD, FACC^_*,_*, Mehmet C. Oz, MD, FACC, Robert N. Sladen, MD, FCCM, Allen H. Graeve, MD, FACS, Robert F. Hebeler, Jr, MD^||, John M. Luber, Jr, MD, FACS^¶, Nicholas G. Smedira, MD, FACC^# on behalf of the NAPA Investigators

^_* Division of Cardiothoracic Surgery, Department of Surgery, Wayne State University School of Medicine, Detroit, Michigan
Division of Cardiothoracic Surgery, College of Physicians & Surgeons, Columbia University, New York, New York
Department of Anesthesiology, College of Physicians & Surgeons, Columbia University, New York, New York
MultiCare Cardiothoracic Surgical Associates, Tacoma General Hospital, Tacoma, Washington
^|| Department of Surgery, Baylor University Medical Center, Dallas, Texas
^¶ Franciscan Health System Research Center, Tacoma, Washington
^# Department of Thoracic and Cardiovascular Surgery, The Cleveland Clinic, Cleveland, Ohio.

Manuscript received August 1, 2006; revised manuscript received September 26, 2006, accepted October 12, 2006.

^_* Reprint requests and correspondence: Dr. Robert M. Mentzer, Jr., Wayne State University School of Medicine, Department of Surgery, Division of Cardiothoracic Surgery, 1241 Scott Hall, 540 E. Canfield, Detroit, Michigan 48201. (Email: rmentzer{at}med.wayne.edu).

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 [ClinicalTrials.gov] )

Abbreviations and Acronyms   CABG = coronary artery bypass grafting   CI = confidence interval   CPB = cardiopulmonary bypass   GFR = glomerular filtration rate   HR = hazard ratio   ICU = intensive care unit   LOS = length of stay   LV = left ventricular   SCr = serum creatinine

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