Carperitide and Atrial Fibrillation After Coronary Bypass Grafting

Abstract

We previously performed a randomized controlled trial of carperitide (Daiichi-Sankyo Pharmaceutical Inc, Tokyo, Japan; Asubio Pharmaceuticals, Inc, Kobe, Japan), which inhibits the renin-angiotensin-aldosterone system (RAAS) and has strong natriuretic activity. We found that carperitide compensated for the adverse effects of extracorporeal circulation and inhibited left ventricular remodeling. [8][9][10][11] In the Nihon University working group study of low-dose HANP Infusion Therapy during cardiac surgery (NU-HIT) for Left Ventricular Dysfunction study, carperitide reduced the incidence of POAF, 8 but an antiarrhythmic effect of carperitide has not been reported in patients with heart failure and the mechanisms involved were unclear. Accordingly, the present study (NU-HIT trial for POAF) was performed to further evaluate the effect of carperitide on POAF and investigate factors related to AF.© 2015 American Heart Association, Inc. Original Article Circ Arrhythm ElectrophysiolBackground-Occurrence of atrial fibrillation after cardiac surgery is associated with long-term mortality. We investigated whether infusion of human atrial natriuretic peptide (carperitide) could prevent postoperative atrial fibrillation. Methods and Results-A total of 668 patients who underwent isolated coronary artery bypass grafting were randomized to receive infusion of carperitide or physiological saline from the initiation of cardiopulmonary bypass. Patients were monitored continuously for 1 week after surgery to detect atrial fibrillation. The risk factors were investigated by Cox proportional hazard model. Postoperative atrial fibrillation occurred in 41 of 335 patients (12.2%) from the carperitide group versus 110 of 333 patients (32.7%) from the placebo group (P<0.0001). Postoperative levels of angiotensin-II, aldosterone, creatine kinase MB isoenzyme, human heart fatty acid-binding protein, and brain natriuretic peptide were all significantly lower in the carperitide group. The risk factors for postoperative atrial fibrillation by the Cox proportional hazard model were an age ≥70 years, emergency surgery, preoperative aldosterone level >150 ng/mL, preoperative nonuse of angiotensin receptor antagonists, preoperative use of calcium antagonists, postoperative nonuse of β-blockers, postoperative nonuse of aldosterone blockers, and nonuse of carperitide. Conclusions-Perioperative Methods Study ProtocolThe NU-HIT trial for POAF was a randomized, double-blind, placebo-controlled study that enrolled patients undergoing isolated coronary artery bypass grafting (CABG) with cardiopulmonary bypass (CPB). Patients who had cardiogenic shock, sinus bradycardia (≤50 per minutes at rest), atrioventricular block, hypothyroidism/hyperthyroidism, a history of AF or other arrhythmia, repeat CABG, and off-pump or on-pump beating CABG were excluded. Subjects were randomized preoperatively by the envelope method to the carperitide group receiving infusion of carperitide from initiation of CPB or the placebo group receiving physiological saline. In Ja...

Effects of Recombinant Human Brain Natriuretic Peptide on Atrial Fibrillation After Coronary Artery Bypass Grafting

“…Studies by Akria Zezai 6,9–11 and colleagues demonstrated that hANP can significantly reduce the incidence of atrial fibrillation after CABG, which prompted the current trial. Furthermore, it not only reduced the incidence of ventricular arrhythmia, but also improved the patient's cardiac and renal function.…”

“…This arrhythmia prevention effect was effective in patients with different conditions such as unstable angina, myocardial infarction, left ventricular ejection fraction <35%, and requiring dialysis. Akria Zezai's research 9 further explored the mechanism of atrial arrhythmia prevention. Patients infused hANP had lower peak and levels of CK-MB and creatinine, higher cGMP levels, and lower levels of renin, angiotensin, and aldosterone.…”

Advancing drug development for atrial fibrillation by prioritising findings from human genetic association studies

“…In two randomised trials of patients receiving cardiopulmonary bypass surgery, peri-operative carperitide infusion compared with placebo significantly reduced the incidence of post-operative AF. 73 , 74 The target NPR3 also has a prioritisation score of >1.…”

Should We Consider Recombinant Human Brain Natriuretic Peptide to Prevent Postoperative Atrial Fibrillation?

“…1 Some studies also explored the function of perioperative infusion of human atrial natriuretic peptide (also known as carperitide) in patients undergoing coronary artery bypass grafting (CABG) with the use of cardiopulmonary bypass, finding a significant reduction of POAF. 9,10 Nevertheless, the role of other natriuretic peptides (NP), such as recombinant human brain natriuretic peptide (rh-BNP), was not explored, and there is a lack of evidence in this field. Natriuretic peptides are 3 biologically active molecules: atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), and C-type natriuretic peptide (CNP).…”