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Journal of Cardiothoracic and Vascular... Dec 2015Emerging studies suggest that administration of levosimendan therapy may be better than dobutamine or placebo in decompensated heart failure. The authors performed an... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
Emerging studies suggest that administration of levosimendan therapy may be better than dobutamine or placebo in decompensated heart failure. The authors performed an updated meta-analysis of trials to obtain the best estimates of the efficacy and safety of levosimendan for the initial treatment of decompensated heart failure.
DESIGN
A meta-analysis.
SETTING
Hospitals.
PARTICIPANTS
A total of 5,349 patients from 25 randomized controlled studies were included in the analysis.
INTERVENTIONS
None.
MEASUREMENTS AND MAIN RESULTS
The authors performed a meta-analysis of trials comparing levosimendan therapy with dobutamine or placebo in patients with decompensated heart failure. Twenty-five trials, involving 5,349 patients, were included. Two reviewers performed independent article review and study quality assessment. Data on overall mortality, early-term mortality, midterm mortality, long-term mortality, efficacy outcomes, and adverse events were collected. Mortality outcomes were according to follow-up duration: early term (≤30-day), midterm (30-day to≤6-month), and long term (>6-month). Levosimendan was compared with dobutamine or placebo, calculating pooled relatives risk (RRs) and associated 95% confidence intervals (CIs). A random-effects model was selected for meta-analysis if there was significant heterogeneity. Levosimendan significantly reduced total mortality (17.1% versus 20.8%; RR, 0.84; 95% CI, 0.75-0.94). Compared with dobutamine, levosimendan was associated with significant reduction in mortality at final follow-up (RR, 0.86; 95% CI, 0.76-0.97; I(2) = 7%; p = 0.02).Compared with placebo, levosimendan was associated with a nonsignificant trend in favor of placebo in mortality at final follow-up (11.6% versus 16.2%, RR, 0.75; 95% CI, 0.56-1.01; p = 0.06), but it was associated with a significant reduction in long-term mortality (RR, 0.34; 95%CI, 0.15-0.76; p = 0.009). Compared with dobutamine or placebo, levosimendan therapy was associated with improvements in hemodynamically- and echocardiographically-derived cardiac parameters. Levosimendan therapy increased the risks of extrasystoles (RR, 1.88; 95% CI, 1.26-2.81), hypotension (RR, 1.33; 95% CI, 1.15-1.53), and headache or migraine (RR, 1.94; 95% CI, 1.54-2.43) when compared with control therapy.
CONCLUSIONS
As compared to placebo or dobutamine, levosimendan in patients with heart failure seemed to have hemodynamic and cardiac benefits. It reduced total mortality and was associated with an increased risk of cardiovascular adverse events.
Topics: Cardiotonic Agents; Heart Failure; Humans; Hydrazones; Pyridazines; Randomized Controlled Trials as Topic; Simendan; Treatment Outcome
PubMed: 26275522
DOI: 10.1053/j.jvca.2015.03.023 -
Journal of Clinical Medicine Jun 2020Vasopressors and inotropes are routinely used in acute myocardial infarction (AMI) related cardiogenic shock (CS) to improve hemodynamics. We aimed to investigate the... (Review)
Review
Vasopressors and inotropes are routinely used in acute myocardial infarction (AMI) related cardiogenic shock (CS) to improve hemodynamics. We aimed to investigate the effect of routinely used vasopressor and inotropes on mortality in AMI related CS. A systematic search of MEDLINE, EMBASE and CENTRAL was performed up to 20 February 2019. Randomized and observational studies reporting mortality of AMI related CS patients were included. At least one group should have received the vasopressor/inotrope compared with a control group not exposed to the vasopressor/inotrope. Exclusion criteria were case reports, correspondence and studies including only post-cardiac surgery patients. In total, 19 studies (6 RCTs) were included, comprising 2478 CS patients. The overall quality of evidence was graded low. Treatment with adrenaline, noradrenaline, vasopressin, milrinone, levosimendan, dobutamine or dopamine was not associated with a difference in mortality between therapy and control group. We found a trend toward better outcome with levosimendan, compared with control (RR 0.69, 95% CI 0.47-1.00). In conclusion, we found insufficient evidence that routinely used vasopressors and inotropes are associated with reduced mortality in patients with AMI related CS. Considering the limited evidence, this study emphasizes the need for randomized trials with appropriate endpoints and methodology.
PubMed: 32629772
DOI: 10.3390/jcm9072051 -
Cureus Sep 2022Septic shock is one of the life-threatening emergencies in hospital settings. Patients with septic shock have been treated with various vasopressors alone as a... (Review)
Review
Septic shock is one of the life-threatening emergencies in hospital settings. Patients with septic shock have been treated with various vasopressors alone as a first-line or in combination with other agents to improve blood pressure and increase the chance of survival. Our study focuses particularly on the efficacy and safety of vasopressin (VP) alone and in combination with other vasopressors. Our study used Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, 2020 to do our systematic review. We searched thoroughly for articles in PubMed, PubMed Central (PMC), Medline, and ScienceDirect. To locate all pertinent papers, we employed the medical subject headings (MeSH) systematic search technique. Twelve papers that were related to the study's issue and passed the quality check were extracted after we applied inclusion/exclusion criteria and reviewed the titles and abstracts. We used a variety of assessment methods for diverse study designs as a quality check. We compared all included studies after reviewing them thoroughly. VP and its synthetic variants (Terlipressin and Selepressin) have always been given as adjuvants to catecholamine, especially with Noradrenaline, in low to moderate doses with continuous infusion in patients with septic shock. Furthermore, VP is a better adjuvant agent than Dopamine and Dobutamine. Though VP has been proven superior to other vasopressors as an adjuvant agent in patients with septic shock, it can cause digital ischemia in high doses.
PubMed: 36258986
DOI: 10.7759/cureus.29143 -
Clinical Research in Cardiology :... Dec 2016Acute heart failure (AHF) with reduced left-ventricular ejection fraction (LVEF) is often a biventricular congested state. The comparative effect of vasodilators and... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Acute heart failure (AHF) with reduced left-ventricular ejection fraction (LVEF) is often a biventricular congested state. The comparative effect of vasodilators and inotropes on the right- and/or left-sided congestion is unknown.
METHODS AND RESULTS
A systematic review, meta-analysis, and meta-regression of AHF studies using pulmonary artery catheter were performed using PubMed, Embase, and Cochrane library. Data from 35 studies, including 3016 patients, were studied. Included patients had a weighted mean age of 60 years, left-ventricular ejection fraction (LVEF) of 24 %, and plasma B-type natriuretic peptide (BNP) of 892 pg/ml. Both the left- and right-ventricular filling pressures were elevated: weighted mean pulmonary artery wedge pressure (PAWP) was 25 mmHg (range 17-31 mmHg) and right atrial pressure (RAP) 12 mmHg (range 7-18 mmHg). Vasodilators and inotropes had similar beneficial effects on PAWP [-6.3 mmHg (95 % CI -7.4 to -5.2 mmHg) and -5.8 mmHg (95 % CI -7.6 to -4.0 mmHg), respectively] and RAP [-2.9 mmHg (95 % CI -3.8 to -2.1 mmHg) and -2.8 mmHg (95 % CI -3.8 to -1.7 mmHg), respectively]. Among inotropes, inodilators, such as levosimendan, have greater beneficial effect on the left-ventricular filling pressure than dobutamine. Drug-induced improvement of PAWP tightly paralleled that of RAP with all studied drugs (r = 0.90, p < 0.001). Vasodilators and inotropes had no short-term effect of renal function.
CONCLUSION
The left- and right-sided filling pressures are similarly improved by vasodilators or inotropes, in AHF with reduced LVEF.
Topics: Cardiotonic Agents; Heart Failure; Humans; Myocardial Contraction; Recovery of Function; Stroke Volume; Treatment Outcome; Vasodilation; Vasodilator Agents; Ventricular Dysfunction, Left; Ventricular Dysfunction, Right; Ventricular Function, Left; Ventricular Function, Right; Ventricular Pressure
PubMed: 27314418
DOI: 10.1007/s00392-016-1009-6 -
ESC Heart Failure Dec 2023Acute kidney injury (AKI) is common in patients with heart failure (HF), but studies have been inconsistent about the incidence of AKI in patients with HF. We conducted... (Meta-Analysis)
Meta-Analysis Review
Acute kidney injury (AKI) is common in patients with heart failure (HF), but studies have been inconsistent about the incidence of AKI in patients with HF. We conducted a meta-analysis to examine the incidence of AKI and its impact on mortality in patients with HF. We also looked at inpatient variables that could predict the development of AKI to identify potential risk factors, so that these can be used as a starting point for intervention and prevention in this group. The Embase, Medline, PubMed, Cochrane libraries, and Web of Science databases were used for searching articles from the inception of the database to October 2022. The EndNote software was used for screening. Meta-analysis was performed using Stata 16.0 software to combine effect sizes. A total of 37 studies were included. Of all the 3 533 583 patients with HF, 774 887 had AKI, with a pooled incidence of 33% [95% confidence interval (CI): 32-35%]. The incidence rate of AKI in acute HF and chronic HF was 36% (95% CI: 31-40%) and 30% (95% CI: 24-35%), respectively. Eleven studies found that AKI patients had higher in-hospital mortality than non-AKI patients [risk ratio (RR): 3.65; 95% CI: 3.04-4.39, P < 0.001]. Mortality was assessed in five studies, and it was found that mortality remained high at 1-year follow-up after onset of AKI (RR: 1.85, 95% CI: 1.54-2.22, P < 0.001). Fifteen admission variables were included and analysed in 13 studies. The combined results showed that diabetes, hypertension, history of chronic kidney disease, chronic HF systolic, age, N-terminal pro-B-type natriuretic peptide, creatinine > 1.0 mg/dL, index estimated glomerular filtration rate < 60 mL/min/1.73 m , blood urea nitrogen > 24 mg/dL, intravenous dobutamine, and serum albumin were predictor factors for HF patients with AKI (P < 0.05). In this meta-analysis, AKI occurred in approximately 33% of HF patients during hospitalization and the risk of dying in the hospital was tripled. Even during 1-year long-term follow-up, the risk of death remained high, and multiple inpatient variables showed that HF patients tended to have AKI. Early intervention and treatment are important to reduce the incidence of AKI and improve the prognosis.
Topics: Humans; Incidence; Heart Failure; Prognosis; Acute Kidney Injury; Risk Factors
PubMed: 37705352
DOI: 10.1002/ehf2.14520 -
European Journal of Heart Failure Jul 2017To perform a meta-analysis and systematic review of published data to assess the relationship between contractile reserve and response to cardiac resynchronization... (Meta-Analysis)
Meta-Analysis Review
AIM
To perform a meta-analysis and systematic review of published data to assess the relationship between contractile reserve and response to cardiac resynchronization therapy (CRT) in patients with heart failure.
METHODS AND RESULTS
We searched MEDLINE/PubMed and Cochrane for all papers published up to 26 April 2016, supplemented by manual searches of reference lists from retrieved articles. The search strategy yielded nine observational studies that met our eligibility criteria with a total of 767 patients of which 757 provided data for this analysis. Contractile reserve after dobutamine infusion was present in 496 patients (66%). During follow-up 474 patients (63%) qualified as CRT responders. The presence of contractile reserve was associated with a higher chance of CRT response (odds ratio 4.42, 95% confidence interval 2.15-9.07, P < 0.001) using a random-effects model. There was evidence of publication bias. Imputation of missing studies attenuated the association to some extent, but the positive association between contractile reserve and CRT response remained with an odds ratio of 2.42 (95% confidence interval 1.17-5.05, P = 0.018).
CONCLUSION
The presence of global contractile reserve at baseline, as assessed by dobutamine stress echocardiography, is associated with a higher chance of CRT response in patients with heart failure.
Topics: Cardiac Resynchronization Therapy; Echocardiography, Stress; Heart Failure; Myocardial Contraction; Prognosis; Stroke Volume; Ventricular Function, Left; Ventricular Remodeling
PubMed: 28233406
DOI: 10.1002/ejhf.768 -
Frontiers in Pharmacology 2024We conducted a systematic review to assess the advantages and disadvantages of levosimendan in patients with sepsis compared with placebo, milrinone, and dobutamine and...
We conducted a systematic review to assess the advantages and disadvantages of levosimendan in patients with sepsis compared with placebo, milrinone, and dobutamine and to explore the clinical efficacy of different concentrations of levosimendan. PubMed, Web of Science, Cochrane Library, Embase, CNKI, Wanfang data, VIP, and CBM databases were searched using such keywords as simendan, levosimendan, and sepsis. The search time was from the establishment of the database to July 2023. Two researchers were responsible for literature screening and data collection respectively. After the risk of bias in the included studies was evaluated, network meta-analysis was performed using R software gemtc and rjags package. Thirty-two randomized controlled trials (RCTs) were included in the network meta-analysis. Meta-analysis results showed that while levosimendan significantly improved CI levels at either 0.1 µg/kg/min (mean difference [MD] [95%CrI] = 0.41 [-0.43, 1.4]) or 0.2 µg/kg/min (MD [95%CrI] =0.54 [0.12, 0.99]). Levosimendan, at either 0.075 µg/kg/min (MD [95% CrI] =0.033 [-0.75, 0.82]) or 0.2 µg/kg/min (MD [95% CrI] = -0.014 [-0.26, 0.23]), had no significant advantage in improving Lac levels. Levosimendan, at either 0.1 µg/kg/min (RR [95% CrI] = 0.99 [0.73, 1.3]) or 0.2 µg/kg/min (RR [95% CrI] = 1.0 [0.88, 1.2]), did not have a significant advantage in reducing mortality. The existing evidence suggests that levosimendan can significantly improve CI and lactate levels in patients with sepsis, and levosimendan at 0.1 µg/kg/min might be the optimal dose. Unfortunately, all interventions in this study failed to reduce the 28-day mortality. https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023441220.
PubMed: 38523635
DOI: 10.3389/fphar.2024.1358735 -
Cardiology Journal 2021
Meta-Analysis
Topics: Cardiotonic Agents; Dobutamine; Heart Failure; Humans; Hydrazones; Pyridazines; Simendan; Treatment Outcome
PubMed: 33843036
DOI: 10.5603/CJ.a2021.0037 -
Internal Medicine Journal Feb 2022An abnormal left ventricular contractile reserve is often seen in patients undergoing stress echocardiogram and may indicate the presence of obstructive coronary artery... (Review)
Review
An abnormal left ventricular contractile reserve is often seen in patients undergoing stress echocardiogram and may indicate the presence of obstructive coronary artery disease. The techniques and indexes used to identify abnormal left ventricular contractile response and its prognostic value in the absence of known causes has not been well studied. To describe the characteristics and clinical outcomes associated with an abnormal left ventricular contractile response, we performed a systematic review that identified 27 eligible studies. A diverse range of indices were utilised to measure left ventricular contractile reserve, most commonly Δleft ventricular ejection fraction in 11 studies. Dobutamine stress echocardiogram was the most commonly performed modality (19 studies) followed by exercise stress echocardiogram (4 studies), dipyridamole stress echocardiogram (2 studies), invasive hemodynamic measurement (1 study) and dobutamine stress magnetic resonance imaging (1 study). All but one study demonstrated a significant association between the absence of left ventricular contractile reserve and increased rate of cardiovascular events, cardiac death and all-cause mortality.
Topics: Dobutamine; Echocardiography, Stress; Heart Ventricles; Humans; Myocardial Contraction; Stroke Volume; Ventricular Dysfunction, Left
PubMed: 35015318
DOI: 10.1111/imj.14995 -
European Journal of Anaesthesiology Aug 2022Low cardiac output syndrome (LCOS) after congenital cardiac surgery has an incidence of up to 25%. Preventing and treating LCOS is of pivotal importance as LCOS is... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Low cardiac output syndrome (LCOS) after congenital cardiac surgery has an incidence of up to 25%. Preventing and treating LCOS is of pivotal importance as LCOS is associated with excess morbidity and mortality.
OBJECTIVES
This systematic review assesses the safety and efficacy of peri-operative levosimendan administration in the setting of paediatric cardiac surgery.
DESIGN
Systematic review of randomised controlled trials. Meta-analyses were performed on efficacy and exploratory outcomes.
DATA SOURCES
Literature was searched in the following databases (MEDLINE, EMBASE, Web of Science and CENTRAL) from inception to July 2021.
ELIGIBILITY CRITERIA
Randomised controlled trials comparing levosimendan with other inotropes or placebo in children younger than 18 years of age undergoing cardiac surgery.
RESULTS
Nine studies enrolling a total of 539 children could be included in the systematic review. All trials study the prophylactic administration of levosimendan in comparison with placebo ( n = 2), milrinone ( n = 6) or dobutamine ( n = 1). Levosimendan dosing varied considerably with only three studies using a loading dose. Levosimendan reduced the incidence of LCOS [risk ratio (RR) 0.80] [95% confidence interval (CI), 0.40 to 0.89, P = 0.01] and increased cardiac index (MD 0.17 l min -1 m -2 ) (95% CI, 0.06 to 0.28, P = 0.003) without affecting other outcomes (mortality, ICU length of stay, hospital length of stay, duration of mechanical ventilation, serum lactate, central venous oxygen saturation, serum creatine or acute kidney injury).
CONCLUSION
The prophylactic use of levosimendan in children undergoing cardiac surgery reduced the incidence of LCOS and increased cardiac index compared with other inotropes or placebo. This effect did not translate into an improvement of other clinical endpoints.
Topics: Anesthesiology; Cardiac Output, Low; Cardiotonic Agents; Child; Humans; Hydrazones; Pyridazines; Simendan
PubMed: 35792892
DOI: 10.1097/EJA.0000000000001711