Washington, DC - Perioperative infusion of nesiritide (Natrecor, Scios) apparently averted kidney damage in patients with chronic heart failure, especially those already with impaired renal function, who underwent on-pump coronary artery bypass graft (CABG) surgery in a randomized, placebo-controlled safety study [1]. As compared with controls, those who received the synthetic brain-type natriuretic peptide, labeled for the relief of dyspnea in patients with acute decompensated HF, also spent less time hospitalized.

As many as a quarter or more of patients undergoing surgery with cardiopulmonary bypass (CPB) develop postoperative renal dysfunction, which can be life threatening, observes Dr Robert F Hebeler, Jr (Baylor University Medical Center, Dallas, TX). Nesiritide's potential for lessening the damage "would be big in terms of patient care," he told heartwire. And the reduced hospitalization time, he added, "certainly bodes well for cost-effectiveness."

In the trial, called Nesiritide Administered Peri-Anesthesia in Patients Undergoing Cardiac Surgery (NAPA), nesiritide was associated with a significantly reduced rate of postoperative renal dysfunction, defined as elevations in serum creatinine (SCr) >0.5 mg/dL. Improvements in glomerular filtration rate (GFR) and urine output were also observed.

Hebeler reported the findings here at the 7th Scientific Forum on Quality of Care and Outcomes Research in Cardiovascular Disease and Stroke sponsored by the American Heart Association. The trial's 30-day safety results are scheduled for online publication in Circulation on May 30, 2006. He said the patients' 180-day clinical outcomes would be presented at a future date.

The trial randomized 303 patients with LV dysfunction and NYHA class 2-4 HF at 54 centers who were undergoing CPB-supported CABG with or without a mitral-valve procedure to receive nesiritide, initiated during anesthesia, at 0.01 µg/kg per minute for 24 to 96 hours. The safety analysis ultimately consisted of 279 patients. Patients in the two arms were treated with diuretics to about the same degree.

Although randomized studies of nesiritide in acute HF have been rare, the authors of observational and dose-finding studies in that clinical setting have generally concluded that the drug either improves or at least has little effect on kidney function, while reducing the need for conventional diuretics. There is some rationale for hoping the drug is renoprotective in some cardiac surgical patients, according to Hebeler. Such surgery with cardioplegia and CPB support "generates neurohormonal changes that are very much like acute heart failure." That physiologic reaction might potentially worsen HF in a patient already with poor LV function, he noted.

As extensively reported by heartwire, there remains a high-profile controversy as to whether other interpretations of the same data suggest the drug may cause substantial harm. After the NAPA study enrolled its last patient, according to Hebeler, a combined analysis of nesiritide studies in acute HF suggested that the drug elevates SCr and so might be renotoxic [2]. The study's authors subsequently reported a similar analysis that hinted at a possible worsening of 30-day mortality [3]. Some scoffed at both allegations, some accepted them as possibilities, many called for further research to explore the issue, and a few questioned whether nesiritide should remain on the market [4].

Hebeler observed that nesiritide at high dosages may have been associated with elevated SCr, but not when infusions were given according to the now-standard regimen, which was used in NAPA. The study, he said, shows that "at the recommended doses, not only is there not a significant deterioration [in renal function], but there's actually some protection." And as a randomized, placebo-controlled trial, according to the surgeon, NAPA "really does accurately reflect the effect of the drug in a much cleaner way than has been done before."