Patients undergoing CABG with renal dysfunction who received infusion of carperitide, a human atrial natriuretic peptide (hANP), were less likely to experience a cardiac event or require dialysis one year after surgery, according to a randomized controlled trial in the Aug. 23 issue of the Journal of the American College of Cardiology. Despite these promising results, many questions still remain about these types of therapeutic agents.
The study, based on the NU-HIT (Nihon University Working Group Study of Low-Dose hANP Infusion Therapy During Cardiac Surgery) trial, showed a renal-protective effect during both the early and longer term post-operative stages.
Therapeutic agents, such as hANP, available as carperitide (Daiichi-Sankyo Pharmaceutical and Asubio Pharmaceuticals) in Japan, and B-type natriuretic peptide (BNAP), available as nesiritide (Natrecor, Johnson & Johnson) in the U.S., caused the authors of an accompanying editorial to question the results.
Akira Sezai, MD, PhD, from the Nihon University School of Medicine in Tokyo, and colleagues used NU-HIT to assess the impact of a low-dose carperitide infusion versus placebo on patients with chronic kidney disease (CKD) undergoing CABG at the Nihon University Itabashi Hospital, also located in Tokyo.
CKD, defined as estimated glomerular filtration rate (eGFR) of 60 ml/min. or less, is an independent predictor of adverse cardiovascular events and CKD patients who undergo surgery are at higher risk of progressing to end-stage kidney disease and dialysis. Previous studies by the authors found that carperitide showed some benefits after cardiopulmonary bypass surgery.
“Because carperitide inhibits the renin-angiotensin-aldosterone system and has a potent natriuretic effect, we have found that it can compensate for the adverse effects of extracorporeal circulation and can inhibit left ventricular remodeling,” Sezai et al wrote.
The researchers enrolled 285 patients between March 1997 and March 2009 and randomized them into a carperitide group (141 patients) and a placebo group (144 patients). Primary endpoints, all post-operative, were measured as the dialysis-free rate after one year and serum creatinine and eGFR at zero, one, three days, one week and one month. Secondary endpoints included early post-operative outcome; post-operative outcome at one year; maximum serum creatinine and rate of increase in serum creatinine.
Overall survival rates were similar for the carperitide group and the placebo group, but the cardiac event-free rate for the carperitide group was significantly higher (82.3 percent vs. 61.8 percent for the placebo group). Post-operative serum creatinine was significantly lower in the carperitide group, and the one-year dialysis-free rate was significantly higher, with 98.6 percent of the carperitide group dialysis-free compared to 91.6 percent of the placebo group.
“Carperitide is not considered to have any long-term pharmaceutical effects, but the cardiorenal protective effects of carperitide in the acute period are considered to result in good long-term effects (avoiding dialysis and cardiac events),” Sezai and colleagues wrote. “We showed that carperitide not only provided renal protection in the acute stage but also over the long term.”
Guido Boerrigter, MD, and John C. Burnett Jr., MD, of Mayo Clinic in Rochester, Minn., provided an overview of cardiovascular disease trials that tested natriuretic peptides as therapeutics. “[They] have led to at times promising, neutral or disconcerting results as it relates to overall benefit and renal function,” they pointed out. They listed questions that as yet have not been addressed and urged that research continue.