Dataset Information

First-Line Antiarrhythmic Transplacental Treatment for Fetal Tachyarrhythmia: A Systematic Review and Meta-Analysis.

ABSTRACT:

Background

There is no consensus on the most effective and best tolerated first-line antiarrhythmic treatment for fetal tachyarrhythmia. The purpose of this systematic review and meta-analysis was to compare the efficacy, safety, and fetal-maternal tolerance of first-line monotherapies for fetal supraventricular tachycardia and atrial flutter.

Methods and results

A comprehensive search of several databases was conducted through January 2017. Only studies that made a direct comparison between first-line treatments of fetal tachyarrhythmia were included. Outcomes of interest were termination of fetal tachyarrhythmia, fetal demise, and maternal complications. Ten studies met inclusion criteria, with 537 patients. Overall, 291 patients were treated with digoxin, 137 with flecainide, 102 with sotalol, and 7 with amiodarone. Digoxin achieved a lower rate of supraventricular tachycardia termination compared with flecainide (odds ratio [OR]: 0.773; 95% confidence interval [CI], 0.605-0.987; I²=34%). In fetuses with hydrops fetalis, digoxin had lower rates of tachycardia termination compared with flecainide (OR: 0.412; 95% CI, 0.268-0.632; I²=0%). There was no significant difference in the incidence of maternal side effects between digoxin and flecainide groups (OR: 1.134; 95% CI, 0.129-9.935; I²=80.79%). The incidence of maternal side effects was higher in patients treated with digoxin compared with sotalol (OR: 3.148; 95% CI, 1.468-6.751; I²=0%). There was no difference in fetal demise between flecainide and digoxin (OR: 0.767; 95% CI, 0.140-4.197; I²=44%).

Conclusions

Flecainide may be more effective treatment than digoxin as a first-line treatment for fetal supraventricular tachycardia.

SUBMITTER: Alsaied T

PROVIDER: S-EPMC5779032 | biostudies-literature | 2017 Dec

REPOSITORIES: biostudies-literature

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Publications

First-Line Antiarrhythmic Transplacental Treatment for Fetal Tachyarrhythmia: A Systematic Review and Meta-Analysis.

Alsaied Tarek T Baskar Shankar S Fares Munes M Alahdab Fares F Czosek Richard J RJ Murad Mohammad Hassan MH Prokop Larry J LJ Divanovic Allison A AA

Journal of the American Heart Association 20171215 12

<h4>Background</h4>There is no consensus on the most effective and best tolerated first-line antiarrhythmic treatment for fetal tachyarrhythmia. The purpose of this systematic review and meta-analysis was to compare the efficacy, safety, and fetal-maternal tolerance of first-line monotherapies for fetal supraventricular tachycardia and atrial flutter.<h4>Methods and results</h4>A comprehensive search of several databases was conducted through January 2017. Only studies that made a direct compari ...[more]

PMID: 29246961

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Project description:Fetal arrhythmia develops in 0.1-5% of pregnancies and may cause fetal heart failure and fetal hydrops, thus increasing fetal, neonatal, and infant mortality. The timely initiation of transplacental antiarrhythmic therapy (ART) promotes the conversion of fetal tachycardia to sinus rhythm and the regression of the concomitant non-immune fetal hydrops. The optimal treatment regimen search for the fetus with tachyarrhythmia is still of high value. Polymorphisms of these genes determines the individual features of the drug pharmacokinetics. The aim of this study was to study the pharmacokinetics of transplacental anti-arrhythmic drugs in the fetal therapy of arrhythmias using HPLC-MS/MS, as well as to assess the effect of the multidrug-resistance gene ABCB1 3435C > T polymorphism on the efficacy and maternal/fetal complications of digoxin treatment. The predisposition to a decrease in the bioavailability of the digoxin in patients with a homozygous variant of the CC polymorphism showed a probable association with the development of ART side effects. A pronounced decrease in heart rate in women with the 3435TT allele of the ABCB1 gene was found. The homozygous TT variant in the fetus showed a probable association with an earlier response to ART and rhythm disruptions on the digoxin dosage reduction. high-performance liquid chromatography with tandem mass spectrometry (HPLC-MS/MS) methods for digoxin and sotalol therapeutic drug monitoring in blood plasma, amniotic fluid, and urine were developed. The digoxin and sotalol concentrations were determined in the plasma blood, urine, and amniotic fluid of 30 pregnant women at four time points (from the beginning of the transplacental antiarrhythmic therapy to delivery) and the plasma cord blood of 30 newborns. A high degree of correlation between the level of digoxin and sotalol in maternal and cord blood was found. The ratio of digoxin and sotalol in cord blood to maternal blood was 0.35 (0.27 and 0.46) and 1.0 (0.97 and 1.07), accordingly. The digoxin concentration in the blood of the fetus at the moment of the first rhythm recovery episode, 0.58 (0.46, 0.8) ng/mL, was below the therapeutic interval. This confirms the almost complete transplacental transfer of sotalol and the significant limitation in the case of digoxin. Previously, ABCB1/P-glycoprotein had been shown to limit fetal exposure to drugs. Further studies (including multicenter ones) to clarify the genetic features of the transplacental pharmacokinetics of antiarrhythmic drugs are needed.

Project description:Background: Fetal arrhythmias are common cardiac abnormalities associated with high mortality due to ventricular dysfunction and heart failure, particularly when accompanied by hydrops. Although several types of common fetal tachycardias have been relatively identified medications, such as digoxin, flecainide, and sotalol, there is no first-line drug treatment protocol established for the treatment of various types of fetal tachycardias. Methods: We conducted a network meta-analysis using a Bayesian hierarchical framework to obtain a model for integrating both direct and indirect evidence. All tachycardia types (Total group), supraventricular tachycardia (SVT subgroup), atrial flutter (AF subgroup), hydrops subgroup, and non-hydrops subgroup fetuses were analyzed, and five first-line regimens were ranked according to treatment outcomes: digoxin monotherapy (D), flecainide monotherapy (F), sotalol monotherapy (S), digoxin plus flecainide combination therapy (DF), and digoxin plus sotalol combination therapy (DS). Effectiveness and safety were determined according to the cardioversion rate and intrauterine death rate. Results: The pooled data indicated that DF combination therapy was always superior to D monotherapy, regardless of the tachycardia type or the presence of hydrops: Total, 2.44 (95% CrI: 1.59, 3.52); SVT, 2.77 (95% CrI: 1.59, 4.07); AF, 67.85 (95% CrI: 14.25, 168.68); hydrops, 6.03 (95% CrI: 2.54, 10.68); and non-hydrops, 5.06 (95% CrI: 1.87, 9.88). DF and F had a similar effect on control of fetal tachycardias. No significant differences were observed when comparing S, DS with D therapies across the subgroup analyses for the SVT, hydrops, and non-hydrops groups. No significant differences in mortality risks were among the various treatment regimens for the total group. And no significant differences were found in rates of intrauterine death rates at the same cardioversion amount. Conclusion The flecainide monotherapy and combination of digoxin and flecainide should be considered the most superior therapeutic strategies for fetal tachycardia. Systematic Review Registration: (https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=288997), identifier (288997).

Project description:ImportanceThe effectiveness of triplet therapy compared with androgen pathway inhibitor (API) doublets in a heterogeneous patient population with metastatic castration-sensitive prostate cancer (mCSPC) is unknown.ObjectiveTo assess the comparative effectiveness of contemporary systemic treatment options for patients with mCSPC across clinically relevant subgroups.Data sourcesFor this systematic review and meta-analysis, Ovid MEDLINE and Embase were searched from each database's inception (MEDLINE, 1946; Embase, 1974) through June 16, 2021. Subsequently, a "living" auto search was created with weekly updates to identify new evidence as it became available.Study selectionPhase 3 randomized clinical trials (RCTs) assessing first-line treatment options for mCSPC.Data extraction and synthesisTwo independent reviewers extracted data from eligible RCTs. The comparative effectiveness of different treatment options was assessed with a fixed-effect network meta-analysis. Data were analyzed on July 10, 2022.Main outcomes and measuresOutcomes of interest included overall survival (OS), progression-free survival (PFS), grade 3 or higher adverse events, and health-related quality of life.ResultsThis report included 10 RCTs with 11 043 patients and 9 unique treatment groups. Median ages of the included population ranged from 63 to 70 years. Current evidence for the overall population suggests that the darolutamide (DARO) triplet (DARO + docetaxel [D] + androgen deprivation therapy [ADT]; hazard ratio [HR], 0.68; 95% CI, 0.57-0.81), as well as the abiraterone (AAP) triplet (AAP + D + ADT; HR, 0.75; 95% CI, 0.59-0.95), are associated with improved OS compared with D doublet (D + ADT) but not compared with API doublets. Among patients with high-volume disease, AAP + D + ADT may improve OS compared with D + ADT (HR, 0.72; 95% CI, 0.55-0.95) but not compared with AAP + ADT, enzalutamide (E) + ADT, and apalutamide (APA) + ADT. For patients with low-volume disease, AAP + D + ADT may not improve OS compared with APA + ADT, AAP + ADT, E + ADT, and D + ADT.Conclusions and relevanceThe potential benefit observed with triplet therapy must be interpreted with careful accounting for the volume of disease and the choice of doublet comparisons used in the clinical trials. These findings suggest an equipoise to how triplet regimens compare with API doublet combinations and provide direction for future clinical trials.

Project description:ImportanceTo our knowledge, evidence-based recommendations on the intratympanic vs systemic administration of corticosteroids for the treatment of idiopathic sudden sensorineural hearing loss remain unestablished, and contradictory conclusions have been reported in previous meta-analyses.ObjectiveTo compare recovery from idiopathic sudden sensorineural hearing loss based on systemic, intratympanic, or a combined treatment with corticosteroids as first-line treatment.Data sourcesWe adhered to the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. We searched PubMed, Embase, OvidSP, CINAHL, and Cochrane Library from January 1, 1966, to July 1, 2018. This study was registered in the International Prospective Register of Systematic Reviews (CRD42018109314).Study selectionWe included randomized studies. Included studies must have excluded identifiable causes. Corticosteroids must have been administered solitarily. We excluded studies that did not define hearing loss as a minimum 30 dB within 72 hours.Data extraction and synthesisWe identified 170 titles, of which 56 (32.9%) were eligible for full-text screening. We independently extracted data. We applied a fixed-effects model to investigate our objectives.Main outcomes and measureWe aimed to (1) estimate the difference in mean pure tone average (PTA) gain in decibels from intratympanic treatment vs systemic treatment and (2) investigate odds ratios for recovery between the different treatment groups.ResultsWe included 7 eligible studies. A total of 710 patients were allocated to receive either intratympanic treatment (IT group, 235 [33%]), systemic treatment (ST group; 325 [46%]) or combined intratympanic and systemic treatment (CB group; 150 [21%]). The PTA was measured by taking the mean of 4 frequencies: 4 studies measured at 500, 1000, 2000, and 3000 Hz and 3 studies measured at 500, 1000, 2000, and 4000 Hz. The ST group had a 2.01-dB higher PTA gain (95% CI, -5.61 dB to 1.59 dB; P?=?.96; I2?=?0%) compared with the IT group and the odds for achieving complete recovery was not significantly different at an odds ratio of 0.94 (95% CI, 0.61 to 1.44; P?=?.19; I2?=?34.5%). For the CB group vs the ST group, the odds ratio was 1.11 (95% CI, 0.68 to 1.82; P?=?.75; I2?=?0%). The analysis of the CB group vs IT group comprised only 2 studies.Conclusions and relevanceThis study does not suggest that corticosteroid delivered intratympanically is more beneficial than systemic treatment in the case of moderate to severe idiopathic sudden sensorineural hearing loss. There were no indications that combined treatment was associated with improved hearing outcomes compared with either systemic or intratympanic treatment.

Dataset Information

First-Line Antiarrhythmic Transplacental Treatment for Fetal Tachyarrhythmia: A Systematic Review and Meta-Analysis.

Background

Methods and results

Conclusions

Publications

First-Line Antiarrhythmic Transplacental Treatment for Fetal Tachyarrhythmia: A Systematic Review and Meta-Analysis.

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