The Efficacy and Safety of Levosimendan in Patients with Advanced Heart Failure: An Updated Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: Intermittent 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. METHODS: Up 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. RESULTS: Fifteen 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). CONCLUSION: In 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. REGISTRATION: PROSPERO identifier number (CRD42023487838).

Efficacy of thoracic endovascular aortic repair versus medical therapy for treatment of type B aortic dissection.

BACKGROUND: Techniques in endovascular therapy have evolved to offer a promising alternative to medical therapy alone for Type B aortic dissections (TBADs). AIM: The aim of this meta-analysis was to compare mortality and overall complications between thoracic endovascular aortic repair (TEVAR) and best medical therapy (BMT) in patients with TBADs. METHODS: We included randomized control trials and prospective or retrospective cohort studies that compared TEVAR and BMT for the treatment of type B aortic dissection. Multiple electronic databases were searched. RESULTS: Thirty-two cohort studies including 150,836 patients were included. TEVAR was associated with a significantly lower 30-day mortality rate than BMT (RR = 0.79, CI = 0.63, 0.99, P = 0.04), notably in patients ≥ 65 years of age (RR = 0.78, CI = 0.64, 0.95, P = 0.01). The TEVAR group had a significantly prolonged hospital stay (MD = 3.42, CI = 1.69, 5.13, P = 0.0001) and ICU stay (MD = 3.18, CI = 1.48, 4.89, P = 0.0003) compared to the BMT. BMT was associated with increased stroke risk (RR = 1.52, CI = 1.29, 1.79, P < 0.00001). No statistically significant differences in late mortality (1, 3, and 5 years) or intervention-related factors (acute renal failure, spinal cord ischemia, myocardial infarction, respiratory failure, and sepsis) were noted between the groups. CONCLUSION: Our meta-analysis revealed a significant association between the TEVAR group and a decreased mortality rate of TBAD compared to the medical treatment group, especially in patients aged 65 years or older. Further randomized controlled trials are needed to confirm our findings.

Efficacy and safety of glucagon-like peptide-1 receptor agonists on prediabetes: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Prediabetes is a condition preceding the development of diabetes and is associated with an increased risk of a number of complications. The primary mode of management is thought to be lifestyle modification. Pharmacological therapy, such as glucagon-like peptide-1 receptor agonists (GLP-1RAs), were not well addressed in the literature and were only evaluated in trials as secondary and exploratory outcomes with a limited sample size. Here, GLP-1RAs are evaluated as a comprehensive therapy approach for patients with prediabetes. METHODS: A comprehensive search of Web of Science, SCOPUS, PubMed, and Cochrane was performed on May 5, 2023, to retrieve randomized controlled trials (RCTs) comparing the effect of GLP-1RAs to placebo and/or lifestyle modification on prediabetes reversion to normoglycemia, prevention of overt diabetes, glycemic control, anthropometric parameters, and lipid profiles. Review Manager (RevMan) version 5.4 was used. The quality of RCTs was assessed using the revised version of the Cochrane Risk of Bias Tool. GRADE was performed to evaluate the certainty of evidence. RESULTS: Twelve trials involving 2903 patients in the GLP-1RAs group and 1413 in the control group were included in the meta-analysis. Low quality of evidence revealed that GLP-1RAs significantly increased the incidence of prediabetes reversion to the normoglycemic state [RR = 1.76, 95% CI (1.45, 2.13), P < 0.00001] and moderate quality of evidence showed that GLP-1RAs significantly prevented new-onset diabetes [RR = 0.28, 95% CI (0.19, 0.43), P < 0.00001]. Significant reductions in HbA1c, fasting plasma glucose, body weight, waist circumference, triglycerides, and LDL were observed in the GLP-1RAs arm (P < 0.05). However, higher incidences of gastrointestinal disorders were reported in the GLP-1RAs group (P < 0.05). CONCLUSIONS: GLP-1RAs combined with lifestyle modification proved to be a more effective therapy for managing prediabetic patients than lifestyle modification alone, with a tolerable safety profile. Future guidelines should consider GLP-1RAs as an adjunct to lifestyle modification in the management of prediabetic patients to provide better management and improve treatment adherence.

Fascia iliaca compartment block for postoperative pain after total hip arthroplasty: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Fascia iliaca compartment block (FICB) is one of the regional nerve blocks used to reduce pain after total hip arthroplasty (THA). We aim to assess the efficacy of FICB in reducing post-operative pain and opioid consumption. METHODS: We searched PubMed, Web of Science, Cochrane Library, Embase, and Scopus on February 19, 2023, and we updated our search in august 2023 using relevant search strategy. Studies were extensively screened for eligibility by title and abstract screening, followed by full-text screening. We extracted the data from the included studies, and then pooled the data as mean difference (MD) or odds ratio (OR) with a 95% confidence interval (CI), using Review Manager Software (ver. 3.5). RESULTS: FIBC significantly reduced analgesic consumption at 24 h (MD = -8.75, 95% CI [-9.62, -7.88] P < 0.00001), and at 48 h post-operatively. (MD = -15.51, 95% CI [-26.45, -4.57], P = 0.005), with a significant sensory block of the femoral nerve (P = 0.0004), obturator nerve (P = 0.0009), and lateral femoral cutaneous nerve (P = 0.002). However, FICB was not associated with a significant pain relief at 6, 24, and 48 h postoperatively, except at 12 h where it significantly reduced pain intensity (MD = -0.49, 95% CI [-0.85, -0.12], P = 0.008). FICB was also not effective in reducing post-operative nausea and vomiting (MD = 0.55, 95% CI [0.21, 1.45], P = 0.23), and was associated with high rates of quadriceps muscle weakness (OR = 9.09, % CI [3.70, 22.30], P = < 0.00001). CONCLUSIONS: FICB significantly reduces the total analgesic consumption up to 48 h; however, it is not effective in reducing post-operative pain, nausea and vomiting and it induced postoperative muscle weakness.

Effect of early metoprolol before PCI in ST-segment elevation myocardial infarction on infarct size and left ventricular ejection fraction. A systematic review and meta-analysis of clinical trials.

AIM: This meta-analysis aims to look at the impact of early intravenous Metoprolol in ST-segment elevation myocardial infarction (STEMI) before percutaneous coronary intervention (PCI) on infarct size, as measured by cardio magnetic resonance (CMR) and left ventricular ejection fraction. METHODS: We searched the following databases: PubMed, Scopus, Cochrane library, and Web of Science. We included only randomized control trials that reported the use of early intravenous Metoprolol in STEMI before PCI on infarct size, as measured by CMR and left ventricular ejection fraction. RevMan software 5.4 was used for performing the analysis. RESULTS: Following a literature search, 340 publications were found. Finally, 18 studies were included for the systematic review, and 8 clinical trials were included in the meta-analysis after the full-text screening. At 6 months, the pooled effect revealed a statistically significant association between Metoprolol and increased left ventricular ejection fraction (LVEF) (%) compared to controls (mean difference [MD] = 3.57, [95% confidence interval [CI] = 2.22-4.92], p < .00001), as well as decreased infarcted myocardium(g) compared to controls (MD = -3.84, [95% [CI] = -5.75 to -1.93], p < .0001). At 1 week, the pooled effect revealed a statistically significant association between Metoprolol and increased LVEF (%) compared to controls (MD = 2.98, [95% CI = 1.26-4.69], p = .0007), as well as decreased infarcted myocardium(%) compared to controls (MD = -3.21, [95% CI = -5.24 to -1.18], p = .002). CONCLUSION: A significant decrease in myocardial infarction and increase in LVEF (%) was linked to receiving Metoprolol at 1 week and 6-month follow-up.