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

Lin

et al. 2021

JCM

Prevention of cardiorenal syndrome through treatment with inotropic agents remains challenging. This network meta-analysis evaluated the safety and renoprotective effects of inotropes on patients with advanced heart failure (HF) using a frequentist random-effects model. A systematic database search was performed until 31 January 2021, and a total of 37 trials were included. Inconsistency, publication bias, and subgroup analyses were conducted. The levosimendan group exhibited significantly decreased mortality compared with the control (odds ratio (OR): 0.62; 95% confidence interval (CI): 0.46–0.84), milrinone (OR: 0.50; 95% CI: 0.30–0.84), and dobutamine (OR: 0.75; 95% CI: 0.57–0.97) groups. In terms of renal protection, levosimendan (standardized mean difference (SMD): 1.67; 95% CI: 1.17–2.18) and dobutamine (SMD: 1.49; 95% CI: 0.87–2.12) more favorably improved the glomerular filtration rate (GFR) than the control treatment did, but they did not significantly reduce the incidence of acute kidney injury. Furthermore, levosimendan had the highest P-score, indicating that it most effectively reduced mortality and improved renal function (e.g., GFR and serum creatinine level), even in patients with renal insufficiency. In conclusion, levosimendan is a safe alternative for protecting renal function on cardiorenal syndrome in patients with advanced HF.

Section: Resultsmentioning

confidence: 99%

“…The risk of bias of each included trial was assessed based on the summative assessment of the field (Supplementary Figure S2). Most of the RCTs exhibited a low risk of bias for the randomization process (37 [100%]) [13,15,18,19,23,, deviations from the intended interventions (23 [62%]) [13,15,18,23,27,29,31,33,34,36,38,[40][41][42][43][44][45][46][47][48]51,53,54], missing outcome data (34 [92%]) [13,15,18,19,23,[27][28][29][30][31][32][33][34][35][36][37][39][40][41]…”

Section: Study Characteristicsmentioning

confidence: 99%

Comprehensive Comparison of the Effect of Inotropes on Cardiorenal Syndrome in Patients with Advanced Heart Failure: A Network Meta-Analysis of Randomized Controlled Trials

Lin

et al. 2021

JCM

“…Levosimendan-nesiritide combination therapy produced the most pronounced improvements during the early stages of treatment, which gradually declined to the same levels produced by monotherapies at day 9 [ 33 ]. Therefore, for patients with ADHF, combination therapies achieved clinical efficacies faster than respective monotherapies, but improvements in the long term may well be similar.…”

Section: Discussionmentioning

confidence: 99%

Use of levosimendan combined with Shenfu injection to treat acute heart failure patients with hypotension: a prospective randomized controlled single-blind study

Zhang

Wan

et al. 2022

BMC Cardiovasc Disord

Background Levosimendan can improve clinical symptoms and the cardiorenal rescue success rate, and stabilize hemodynamic parameters in individuals suffering from acute decompensated heart failure. In addition, Shenfu injection (SFI) has been shown to protect the ischemic heart and enhance myocardial contractility. Methods For this randomized control single-blind study, 101 patients with acute decompensated heart failure (ADHF) were enrolled and randomly assigned to control levosimendan (n = 51) and levosimendan + SFI injection (n = 50) groups. Attending physicians were not blinded for which arm the patients were allocated. Blood pressure, heart rate, the electrocardiogram, respiratory rate, fluid intake and urine output were all recorded 2 h and 24 h after drug infusions had commenced, and the cardiac index (CI) was monitored by ultrasonic cardiac output monitors. Results Median blood pressure was markedly increased in the levosimendan + SFI group after 2 h and 24 h from the initiation of infusions compared to levosimendan administration alone. Brain natriuretic peptide (BNP) concentrations were reduced after administrations of levosimendan + SFI or solely levosimendan (both P < 0.001). Alterations in BNP concentrations were not different in the combination and control groups. No differences were found between the 2 groups in heart rate or severe hypotension, but blood pressure (systolic blood pressure, diastolic blood pressure) and hemodynamic parameters including CI, cardiac output and stroke volume index responded better in the levosimendan + SFI group compared to the monotherapy levosimendan group. Conclusions Levosimendan + SFI was superior to treat ADHF patients compared to levosimendan monotherapy and produced significant improvements in hemodynamic parameters especially for ADHF patients with hypotension. Trail registration The study was prospectively registered at Chinese Clinical Trial Registry with registration number [ChiCTR2000039385] (10/25/2020).

European Heart Journal Supplements

“…In this context, a full evaluation of the impact of using levosimendan in combination with agents such as dobutamine may be instructive: useful insights on that matter should be obtainable from post hoc analysis of data from completed randomized trials supplementing the exploratory work of Nanas et al ., 15 who observed survival advantages from the use of levosimendan with dobutamine (45-day survival rate 61%, vs. 6% with dobutamine only, P = 0.0002 in log-rank test) in patients with AdHF. Reports of the successful use of levosimendan in combination with nesiritide for the relief of symptoms and reduction in 3-month rates of re-admission or death in 120 acute heart failure patients 34 are a further intimation of the utility and potential of levosimendan as an element in such a strategy. Experiences in the ongoing Early Management Strategies of Acute Heart Failure for Patients with NSTEMI (EMSAHF) study (NCT03189901) may provide insights into this premise.…”

Section: Prevention Of Destabilization As a Strategic Goalmentioning

confidence: 99%

Repetitive levosimendan treatment in the management of advanced heart failure

Oliva

Comín‐Colet

Fedele

et al. 2018

Inotropes may be an appropriate treatment for patients with advanced heart failure (AdHF) who remain highly symptomatic despite optimized standard therapies. Objectives for inotrope use in these situations include relief of symptoms and improvement of quality of life, and reduction in unplanned hospitalizations and the costs associated with such episodes. All of these goals must be attained without compromising survival. Encouraging findings with intermittent cycles of intravenous levosimendan have emerged from a range of exploratory studies and from three larger controlled trials (LevoRep, LION-HEART, and LAICA) which offered some evidence of clinical advantage. In these settings, however, obtaining statistically robust data may prove elusive due to the difficulties of endpoint assessment in a complex medical condition with varying presentation and trajectory. Adoption of a composite clinical endpoint evaluated in a hierarchical manner may offer a workable solution to this problem. Such an instrument can explore the proposition that repetitive administration of levosimendan early in the period after discharge from an acute episode of worsening heart failure may be associated with greater subsequent clinical stability vis-à-vis standard therapy. The use of this methodology to develop a ‘stability score’ for each patient means that all participants in such a trial contribute to the overall outcome analysis through one or more of the hierarchical endpoints; this has helpful practical implications for the number of patients needed and the length of follow-up required to generate endpoint data. The LeoDOR study (NCT03437226), outlined in this review, has been designed to explore this new approach to outcome assessment in AdHF.