Levosimendan and Nesiritide as a Combination Therapy in Patients With Acute Heart Failure

• Published in: The American journal of the medical sciences 2015-05, Vol.349 (5), p.398-405
• Main Authors: Jia, Zhi, MS, Guo, Mu, MS, Zhang, Li-Yuan, MS, Zhang, Yun-Qiang, PhD, Liang, Hai-Qing, MS, Song, Yu, MS
• Format: Article
• Language: English
• Subjects: Acute Disease; Aged; Aged, 80 and over; Cardiotonic Agents - administration & dosage; Cardiotonic Agents - adverse effects; Drug Monitoring; Drug Synergism; Drug Therapy, Combination; Female; Heart failure; Heart Failure - drug therapy; Heart Failure - mortality; Heart Failure - physiopathology; Humans; Hydrazones - administration & dosage; Hydrazones - adverse effects; Infusions, Intravenous; Internal Medicine; Levosimendan; Male; Middle Aged; Mortality; Natriuretic Peptide, Brain - administration & dosage; Natriuretic Peptide, Brain - adverse effects; Nesiritide; Patient Readmission; Pyridazines - administration & dosage; Pyridazines - adverse effects; Severity of Illness Index; Treatment Outcome; Ventricular function
• ISSN: 0002-9629; 1538-2990
• DOI: 10.1097/MAJ.0000000000000461

Abstract Background Individually, levosimendan and nesiritide have been associated with substantial clinical benefits for the treatment of acute decompensated heart failure (ADHF). The aim of this study was to evaluate the efficacy of the combination of levosimendan and nesiritide for the treatment of ADHF. Methods One hundred and twenty patients were randomly assigned to control, levosimendan, nesiritide or combination groups. The patients received 2 drugs: 1 was levosimendan or placebo A and the other was nesiritide or placebo B. The primary end points were rates of clinical effectiveness at 1, 3, 5 and 9 days after the start of therapy. Results Nine days after the initiation of drug infusion, the clinical effectiveness rate in the combination group was better than that in the control group (odds ratio: 1.43, 95% confidence interval: 0.46-2.41, P = 0.004). The combination treatment also resulted in higher rates of clinical effectiveness than individually provided levosimendan or nesiritide at 1 day (both P = 0.04) or placebo at 1, 3 or 5 days (P = 0.002, 0.006 and 0.009, respectively). The combination method was associated with fewer deaths and readmissions, as compared with the rate observed in the placebo group during the 3-month follow-up (hazard ratio: 0.43, 95% confidence interval: 0.19-0.96, P = 0.038). Conclusions Among patients with ADHF, intravenous infusion of levosimendan and nesiritide was superior to placebo and single-drug therapies in terms of improvements in clinical conditions during the early stages of therapy.