Efficacy and safety of levosimendan and dobutamine in heart failure: A systematic review and meta-analysis.
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ABSTRACT:
SUBMITTER: Jaguszewski MJ
PROVIDER: S-EPMC8169199 | biostudies-literature | 2021
REPOSITORIES: biostudies-literature
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Efficacy and safety of levosimendan and dobutamine in heart failure: A systematic review and meta-analysis.
Jaguszewski Milosz J MJ Gasecka Aleksandra A Targonski Radoslaw R Filipiak Krzysztof J KJ Szarpak Lukasz L
Cardiology journal 20210412 3
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Project description:Levosimendan and dobutamine are extensively used to treat sepsis-associated cardiovascular failure in ICU. Nevertheless, the role and mechanism of levosimendan in patients with sepsis-induced cardiomyopathy remains unclear. Moreover, previous studies on whether levosimendan is superior to dobutamine are still controversial. More importantly, these studies did not take changes (before-after comparison to the baseline) in quantitative parameters such as ejection fraction into account with the baseline level. Here, we aimed to determine the pros and cons of the two medicines by assessing the changes in cardiac function and blood lactate, mortality, with the standardized mean difference used as a summary statistic. Relevant studies were obtained by a thorough and disciplined literature search in several notable academic databases, including Google Scholar, PubMed, Cochrane Library and Embase until November 2020. Outcomes included changes in cardiac function, lactic acid, mortality and length of hospital stay. A total of 6 randomized controlled trials were included in this study, including 192 patients. Compared with dobutamine, patients treated with levosimendan had a greater improvement of cardiac index (ΔCI) (random effects, SMD = 0.90 [0.20,1.60]; I2 = 76%, P < 0.01) and left ventricular stroke work index (ΔLVSWI) (random effects, SMD = 1.56 [0.90,2.21]; I2 = 65%, P = 0.04), a significant decrease of blood lactate (Δblood lactate) (random effects, MD = - 0.79 [- 1.33, - 0.25]; I2 = 68%, P < 0.01) at 24-h after drug intervention, respectively. There was no significant difference between levosimendan and dobutamine on all-cause mortality in ICU (fixed effect, OR = 0.72 [0.39,1.33]; I2 = 0%, P = 0.99). We combine effect sizes related to different measurement parameters to evaluate cardiac function, which implied that septic patients with myocardial dysfunction might have a better improvement of cardiac function by levosimendan than dobutamine (random effects, SMD = 1.05 [0.69,1.41]; I2 = 67%, P < 0.01). This study suggested a significant improvement of CI, LVSWI, and decrease of blood lactate in septic patients with myocardial dysfunction in ICU after 24-h administration of levosimendan than dobutamine. However, the administration of levosimendan has neither an impact on mortality nor LVEF. Septic patients with myocardial dysfunction may partly benefit from levosimendan than dobutamine, mainly embodied in cardiac function improvement.
| S-EPMC8514594 | biostudies-literature
Project description:AimsWe sought to conduct a meta-analysis regarding the safety and efficacy of sodium-glucose co-transporter 2 (SGLT2) inhibitors in patients with heart failure (HF).Methods and resultsMEDLINE, Scopus, Cochrane CENTRAL, and ClinicalTrials.gov were searched from their inception to November 2020 for placebo-controlled randomized controlled trials of SGLT2 inhibitors. Randomized controlled trials were selected if they reported at least one of the prespecified outcomes in patients with HF. Hazard ratios (HRs) or risk ratios and their corresponding 95% confidence intervals were pooled using a random-effects model. A total of seven trials including 16 820 HF patients (N = 8884 in the SGLT2 inhibitor arms; N = 7936 in the placebo arms) were included. In the overall HF cohort, SGLT2 inhibitors compared with placebo significantly reduced the risk of the composite endpoint of first HF hospitalization or cardiovascular death [HR: 0.77 (0.72-0.83); P < 0.001; I2 = 0%], time to first HF hospitalization [HR: 0.71 (0.64-0.78); P < 0.001; I2 = 0], cardiovascular mortality [HR: 0.87 (0.79-0.96); P = 0.005; I2 = 0%], and all-cause mortality [HR: 0.89 (0.82-0.96); P = 0.004; I2 = 0%]. Results remained consistent across HF-specific trials and according to diabetes mellitus status. A trend towards benefit was observed in patients with HF with preserved ejection fraction for the composite of HF hospitalization and cardiovascular death [HR: 0.80 (0.63-1.00); P = 0.05; I2 = 29%]. No increased risk of hypovolaemia, hyperkalaemia, and hypotension was seen with SGLT2 inhibitors compared with placebo.ConclusionsSGLT2 inhibitors significantly improve cardiovascular outcomes including cardiovascular and all-cause mortality in patients with HF without an increased risk of serious adverse events. A trend towards benefit was observed in patients with HF with preserved ejection fraction.
| S-EPMC7755023 | biostudies-literature
Project description:Objective: 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. Methods: 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. Results: 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. Conclusion: 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. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023441220.
| S-EPMC10957638 | biostudies-literature
Project description:ObjectiveThis study aimed to assess the adjunctive efficacy and safety of Puerarin injection (PI) on acute heart failure (AHF) based on a systematic review and meta-analysis.MethodsNine databases were searched from March 1990 to March 2022 to identify randomized controlled trials (RCTs) related to the adjunctive treatment of PI for AHF. The Cochrane collaboration tool was used to assess the risk of bias in the included studies. Meta-analysis and subgroup and sensitivity analyses were conducted by RevMan 5.3 software. The evidence's certainty was evaluated by grading recommendations assessment, development, and evaluation (GRADE) methods.ResultsA total of 8 studies were included with a total of 614 patients with AHF. The meta-analysis demonstrated that adjunctive treatment with PI on AHF was superior to conventional medicine alone. It increased the total effective rate (RR = 1.38; 95% CI, 1.22-1.55; p < 0.001) and improved left ventricular ejection fraction [SMD = 0.85; 95% CI (0.62, 1.09); p < 0.001]. Regarding safety, a total of 11.9% (23/194) adverse reactions were observed in the PI group and 9.8% (19/194) adverse reactions in the control group, and there were no significant differences in the incident rate of adverse events between both groups [RR = 1.16; 95% CI (0.66-2.05); p = 0.061]. The outcomes' evidentiary quality was assessed as "moderate."ConclusionPI had an adjunctive effect on AHF combined with conventional medicine, and it seemed to be safe and more effective than the conventional medical treatment alone for improving the total clinical effective rate and left ventricular ejection fraction. But further well-designed RCTs are required to confirm the efficacy and safety of XBP in treating AHF due to the poor methodological quality of the included RCTs.Systematic review registration[https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=327636], identifier [CRD42022327636].
| S-EPMC9357890 | biostudies-literature
Project description:PurposeTo evaluate the efficacy and safety of patiromer, a novel potassium binder, in reducing the risk of hyperkalemia in patients with heart failure and optimizing their RAASi therapy.DesignSystematic review and meta-analyses.MethodThe authors conducted a systematic search in Pubmed, Embase, Web of Science, and Cochrane Library for randomized controlled trials investigating the efficacy and safety of patiromer in heart failure patients from inception to 31 January 2023 and updated on 25 March 2023. The primary outcome was the association between the reduction of hyperkalemia and patiromer compared with placebo, and the secondary outcome was the association between optimization of RAASi therapy and patiromer.ResultsA total of four randomized controlled trials (n = 1163) were included in the study. Patiromer was able to reduce the risk of hyperkalemia in heart failure patients by 44% (RR 0.56, 95% CI 0.36 to 0.87; I2 = 61.9%), improve tolerance to target doses of MRA in patients with heart failure (RR 1.15, 95% CI 1.02 to 1.30; I2 = 49.4%), and decrease the proportion of all-cause discontinuation of RAASi (RR 0.49, 95% CI 0.25 to 0.98; I2 = 48.4%). However, patiromer therapy was associated with an increased risk of hypokalemia (RR 1.51, 95% CI 1.07 to 2.12; I2 = 0%), while no other statistically significant adverse events were observed.ConclusionPatiromer appears to have a considerable effect on reducing the incidence of hyperkalemia in heart failure patients and on optimizing the therapy of RAASi in those patients.
| S-EPMC11680614 | biostudies-literature
Project description:BackgroundIntermittent ambulatory levosimendan administration has been shown in several small randomized controlled trials to benefit patients with advanced heart failure, preventing heart failure rehospitalization and mortality. We aim to investigate the totality of high-quality evidence regarding the efficacy and safety of intermittent levosimendan in advanced heart failure patients.MethodsUp to September 2023, we systematically reviewed the randomized controlled trials indexed in PubMed, Embase Cochrane, SCOPUS, and Web of Science. We used mean difference (MD) to estimate the continuous outcomes, and risk ratio (RR) for the dichotomous outcomes with a 95% confidence interval (CI), using the random-effects model. Ultimately, a trial sequential analysis was employed to enhance the reliability of our findings and Grading of Recommendations Assessment, Development, and Evaluation (GRADE) framework for certainty leveling.ResultsFifteen randomized controlled trials with 1181 patients were included. Intermittent levosimendan was significantly associated with an improved left ventricular ejection fraction compared with placebo (MD 6.39 [95% CI 3.04-9.73], P = 0.002; I2 = 75, P = 0.0005), with cumulative z-score of change after ≤ 1 week passing the monitoring boundaries, favoring the levosimendan, but did not cross the required information size. Additionally, levosimendan reduced the all-cause mortality rate (RR 0.60 [95% CI 0.40-0.90], P = 0.01; I2 = 9, P = 0.36). However, we found no difference between levosimendan and placebo in all-cause rehospitalization rate (RR 0.75 [95% CI 0.46-1.22], P = 0.25; I2 = 70, P = 0.04), event-free survival rate (RR 0.97 [95% CI 0.72-1.30], P = 0.84; I2 = 63, P = 0.03), or any adverse event (RR 1 [95% CI 0.73-1.37], P = 1.00, I2 = 0%, P = 0.70).ConclusionIn patients with advanced heart failure, intermittent levosimendan significantly improved left ventricular ejection fraction, brain natriuretic peptide values, and all-cause mortality rate. Levosimendan use is not associated with a change in rehospitalization or event-free survival.RegistrationPROSPERO identifier number (CRD42023487838).
| S-EPMC11525400 | biostudies-literature
Project description:BackgroundHeart failure (HF) is a global health concern, affecting millions of individuals worldwide and leading to significant morbidity and mortality. Despite advances in conventional therapeutic strategies, the prognosis for HF patients remains challenging, and there is a constant search for novel therapeutic options. Among these, Panax quinquefolius saponin (PQS) has demonstrated promising pharmacological properties that may benefit HF. However, the efficacy and safety of PQS for HF have not been comprehensively evaluated.ObjectiveThis systematic review and meta-analysis aim to provide a more reliable estimation of the efficacy and safety of PQS for HF. This will help clinicians make informed decisions regarding the potential use of PQS in managing HF patients.MethodsWe comprehensively and systematically searched for published randomized controlled trials (RCTs) in the following eight electronic databases: PubMed, Cochrane Library, EMBASE, Web of Science (WOS), China National Knowledge Infrastructure (CNKI), China Science and Technology Journal Database (VIP), Wanfang Data, and China Biology Medicine Database (CBM) from database inception to March 2024. The Cochrane risk of bias (ROB 2.0) assessment tool was used for quality assessment, and Review Manager (RevMan, version 5.4) was used for meta-analysis. Mean difference (MD), 95% credible interval (CI), and relative risk (RR) estimates were calculated under a random-effects model. We also used GRADE profiler (GRADEpro, version 3.6) to analyze the quality of outcomes. In addition, the protocol has been registered in International Platform of Registered Systematic Review and Meta-analysis Protocols (INPLASY) under registry number 202440050.ResultsThis study included nine RCTs involving a total of 952 patients with HF. The results of a meta-analysis under a random-effects model showed that adjuvant PQS therapy significantly increased LVEF (MD = 6.23, 95% CI [4.35, 8.12], P < 0.00001), 6MWTD (MD = 25.26, 95% CI [8.23, 42.30], P = 0.004), and decreased BNP/NT-pro-BNP (MD = -187.94, 95% CI [-267.20, -108.67], P < 0.00001), LVEDV (MD = -22.83, 95% CI [-42.79, -2.87], P = 0.02), LVEDD (MD = -4.76, 95% CI [-5.77, -3.74], P < 0.00001), and LVESV (MD = -11.86, 95% CI [-19.89, -3.83], P = 0.004) in patients with HF.ConclusionThe evidence provided by this systematic review suggests that adjunctive PQS therapy for HF can improved clinical efficacy and holds potential advantages in improving cardiac function and increasing exercise tolerance. However, given the limitations inherent in this review, the conclusions of this study should be interpreted cautiously. Therefore, in clinical practice, it is recommended that physicians tailor treatment strategies according to the specific circumstances of individual patients.Systematic review registrationhttps://inplasy.com/?s=202440050.
| S-EPMC11906658 | biostudies-literature
Project description:BackgroundChronic heart failure (CHF), the final phase of various heart diseases, is a serious public health problem resulting in high hospitalization rates, mortality, and increasing health care costs. Nuanxin capsule (NXC), a Chinese herbal formula, has been widely used in the treatment of CHF. However, the safety and efficacy of NXC used in patients with CHF has been uncertain and there has been no standard clinical trial published to confirm this. Thus, we conduct a study to evaluate the safety and efficacy of NXC for CHF.MethodsThe reference lists of randomized controlled trials and 8 electronic databases will be independently and systematically searched by 2 review authors in May 2018. Four English databases (EMBASE, PubMed, Cumulative Index to Nursing and Allied Health Literature [CINAHL], and Cochrane Central Register of Controlled Trials [CENTRAL]) and 4 Chinese databases (Chinese Biomedical Literature Database [CBM], Chinese National Knowledge Infrastructure [CNKI], Wanfang Database, and VIP Database) will be included. The primary outcomes will be assessed according to the function classification of New York Heart Association (NYHA). Data synthesis will be precisely computed using the RevManV5.3 software when a data-analysis is allowed. Methodological quality will be assessed according to Cochrane Handbook.ResultsThis study will provide a high-quality synthesis of current evidence of NXC for CHF from different aspects including the mortality, the function classification of NYHA.ConclusionThe conclusion of this systematic review will provide evidence to prove whether NXC is an effective therapeutic intervention for patient with CHF.PROSPERO registration number: PROSPERO CRD42018090003.
| S-EPMC6076094 | biostudies-literature
Project description:IntroductionAFFIRM-AHF and IRONMAN demonstrated lower rates of the combined endpoint recurrent heart failure (HF) hospitalizations and cardiovascular death (CVD) using intravenous (IV) ferric carboxymaltose (FCM) and ferric derisomaltose (FDI), respectively in patients with HF and iron deficiency (ID) utilizing prespecified COVID-19 analyses.Material and methodsWe meta-analyzed efficacy, between trial heterogeneity and data robustness for the primary endpoint and CVD in AFFIRM-AHF and IRONMAN. As sensitivity analysis, we analyzed data from all eligible exploratory trials investigating FCM/FDI in HF.ResultsFCM/FDI reduced the primary endpoint (RR = 0.81, 95% CI 0.69-0.95, p = 0.01, I2 = 0%), with the number needed to treat (NNT) being 7. Power was 73% and findings were robust with fragility index (FI) of 94 and fragility quotient (FQ) of 0.041. Effects of FCM/FDI were neutral concerning CVD (OR = 0.88, 95% CI 0.71-1.09, p = 0.24, I2 = 0%). Power was 21% while findings were fragile with reverse FI of 14 and reversed FQ of 0.006. The sensitivity analysis from all eligible trials (n = 3258) confirmed positive effects of FCM/FDI on the primary endpoint (RR = 0.77, 95% CI 0.66-0.90, p = 0.0008, I2 = 0%), with NNT being 6. Power was 91% while findings were robust (FI of 147 and FQ of 0.045). Effect on CVD was neutral (RR = 0.87, 95% CI 0.71-1.07, p = 0.18, I2 = 0%). Power was 10% while findings were fragile (reverse FI of 7 and reverse FQ of 0.002). Rate of infections (OR = 0.85, 95% CI 0.71-1.02, p = 0.09, I2 = 0%), vascular disorder (OR = 0.84, 95% CI 0.57-1.25, p = 0.34, I2 = 0%) and general or injection-site related disorders (OR = 1.39, 95% CI 0.88-1.29, p = 0.16, I2 = 30%) were comparable between groups. There was no relevant heterogeneity (I2 > 50%) between the trials for any of the analyzed outcomes.ConclusionsUse of FCM/FDI is safe and reduces the composite of recurrent HF hospitalizations and CVD, while effects on CVD alone are based on available level of data indeterminate. Findings concerning composite outcomes exhibit a high level of robustness without heterogeneity between trials with FCM and FDI.
| S-EPMC10116902 | biostudies-literature
Project description:BackgroundControversy has persisted over the clinical benefits of low-dose sacubitril/valsartan in patients with heart failure (HF).HypothesisLow-dose sacubitril/valsartan might also be effective and safe in HF patients.MethodsElectronic databases including PubMed, Ovid, and Cochrane Library were systematically retrieved from inception to August 5, 2021. Review manager 5.4 and Stata 15.1 were employed in this systematic review and meta-analysis. Key efficacy outcomes of interest included HF hospitalization, all-cause mortality, left ventricular ejection fraction (LVEF), N-terminal pro-B-type natriuretic peptide (NT-proBNP), together with New York Heart Association (NYHA) functional class. The safety outcome was systolic blood pressure (SBP). The grading of recommendations assessment, development, and evaluation approach was conducted to evaluate the quality of evidence for each outcome.ResultsA total of 1269 studies were screened and 9 real-world studies met the inclusion criteria were included in the meta-analysis, with 1697 participants. Compared with low-dose sacubitril/valsartan, high-dose sacubitril/valsartan significantly reduced the risk of HF hospitalization (odds ratio [OR]: 0.4, 95% confidence interval [CI]: 0.27-0.61, p < .0001) and the risk of all-cause mortality (OR: 0.23, 95% CI: 0.11-0.47, p < .0001). However, there were no appreciable differences in improvements of NYHA (OR: 0.59, 95% CI: 0.15-2.35, p = .45), changes of LVEF (mean difference [MD]: 2.73%, 95% CI: -2.24% to 7.7%, p = .28), changes of NT-proBNP (MD: 43.09, 95% CI: -28.41 to 114.59, p = .24) and changes of SBP (MD: 3.01, 95% CI: -4.62 to 10.64, p = .44) between groups with low-dose and high-dose sacubitril/valsartan.ConclusionsCompared with high-dose sacubitril/valsartan, low-dose sacubitril/valsartan was associated with increased risks of HF hospitalization and all-cause mortality. However, no distinct between-group differences in improvements of NYHA, changes of LVEF, changes of NT-proBNP and changes of SBP were observed.
| S-EPMC10018087 | biostudies-literature