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Phytomedicine : International Journal... Jan 2022The combination of antiarrhythmic drugs with traditional Chinese formulas are used treatments for the management of paroxysmal atrial fibrillation (PAF). However, the... (Meta-Analysis)
Meta-Analysis
Investigating the efficiency and tolerability of traditional Chinese formulas combined with antiarrhythmic agents for paroxysmal atrial fibrillation: A systematic review and Bayesian network meta-analysis.
BACKGROUND
The combination of antiarrhythmic drugs with traditional Chinese formulas are used treatments for the management of paroxysmal atrial fibrillation (PAF). However, the most effective treatment for PAF has yet to be been determined. A Bayesian network meta-analysis study was thus performed for comparing the relative efficacy and tolerability of different treatment alternatives.
METHODS
A comprehensive literature review of randomized controlled trials (RCTs) is performed from eight database. Maintenance rate of sinus rhythm (MRSR), p-wave dispersion (Pd), left atrium diameter (LAD), left ventricular ejection fraction (LVEF), and adverse events (AEs) were used as outcomes. We also estimated treatment rank based on the surface under the cumulative ranking curve (SUCRA). This study was performed using a Bayesian network meta-analysis with a random-effects model.
FINDINGS
After screening, 59 RCTs involving 5,543 patients and 16 treatments were included. The results showed that Shensong-Yangxin capsule (SSYX) plus amiodarone (81%) was the most effective treatment for MRSR according to the value of SUCRA, followed by Wenxin-Keli granules (WXKL) plus amiodarone (73%). Meanwhile, SSYX plus amiodarone (7%) was most likely to reduce Pd, followed by SSYX plus metoprolol (23%), WXKL plus amiodarone (26%), WXKL plus bisoprolol (27%). Furthermore, SSYX plus amiodarone (4%) was more effective in improving LAD. WXKL plus amiodarone was preferred because it had the lowest toxicity. For benefit-risk ratio, amiodarone combined with WXKL or SSYX appeared to be the best option.
CONCLUSION
Antiarrhythmic agents combined with traditional Chinese formulas had higher efficacy and lower toxicity than other treatment alternatives. This study might provide reference to help find the better treatment options for PAF.
Topics: Anti-Arrhythmia Agents; Atrial Fibrillation; China; Humans; Network Meta-Analysis
PubMed: 34781230
DOI: 10.1016/j.phymed.2021.153832 -
Cardiovascular Drugs and Therapy Aug 2023Non-vitamin K antagonist oral anticoagulants (NOACs) are excreted by P-glycoprotein (P-gp) and some are metabolized by CYP450 enzymes such as CYP3A4. Although fewer drug... (Meta-Analysis)
Meta-Analysis Review
Non-vitamin K Antagonist Oral Anticoagulants (NOACs) Versus Warfarin in Patients with Atrial Fibrillation Using P-gp and/or CYP450-Interacting Drugs: a Systematic Review and Meta-analysis.
PURPOSE
Non-vitamin K antagonist oral anticoagulants (NOACs) are excreted by P-glycoprotein (P-gp) and some are metabolized by CYP450 enzymes such as CYP3A4. Although fewer drug interactions are present with NOACs, it is unclear whether NOACs should also be preferred over vitamin K antagonists (VKAs) in patients with atrial fibrillation (AF) using pharmacokinetically interacting drugs. Therefore, the benefit-risk profile of NOACs versus VKAs was investigated in AF patients treated with P-gp and/or CYP450-interacting drugs.
METHODS
Using PubMed and Embase, randomized controlled trials and observational studies on the effectiveness and safety of NOACs versus VKAs in AF patients using P-gp and/or CYP450-interacting drugs were included. A meta-analysis was performed, calculating relative risks (RR) and 95% confidence intervals (CI) with the Mantel-Haenszel method.
RESULTS
Twelve studies were included, investigating 10,793 NOAC and 10,096 VKA users treated with P-gp/CYP3A4 inhibitors, whereas no studies on P-gp and/or CYP450-inducing drugs were identified. Compared to VKAs, NOACs were associated with a borderline non-significantly lower stroke or systemic embolism (stroke/SE) risk (RR 0.85, 95%CI (0.72-1.01)), significantly lower intracranial bleeding (RR 0.47, 95%CI (0.34-0.65)) and all-cause mortality risks (RR 0.87, 95%CI (0.79-0.95), but significantly higher gastrointestinal bleeding risk (RR 1.74, 95%CI (1.06-2.86)). Among AF patients using amiodarone, NOACs were associated with significantly lower stroke/SE (RR 0.71, 95%CI (0.54-0.93)) and intracranial bleeding risks (RR 0.51, 95%CI (0.29-0.88)), but significantly higher gastrointestinal bleeding risk (RR 2.15, 95%CI (1.24-3.72)) than VKAs.
CONCLUSION
The benefit-risk profile of NOACs compared to VKAs was preserved in AF patients using P-gp/CYP3A4 inhibitors, including amiodarone.
Topics: Humans; Warfarin; Anticoagulants; Atrial Fibrillation; ATP Binding Cassette Transporter, Subfamily B, Member 1; Administration, Oral; Cytochrome P-450 CYP3A Inhibitors; Stroke; Intracranial Hemorrhages; Gastrointestinal Hemorrhage; Embolism; Amiodarone
PubMed: 34637052
DOI: 10.1007/s10557-021-07279-8 -
Journal of Cardiac Surgery Oct 2021Vasoplegic syndrome (VPS) is defined as systemic hypotension due to profound vasodilatation and loss of systemic vascular resistance (SVR), despite normal or increased...
BACKGROUND
Vasoplegic syndrome (VPS) is defined as systemic hypotension due to profound vasodilatation and loss of systemic vascular resistance (SVR), despite normal or increased cardiac index, and characterized by inadequate response to standard doses of vasopressors, and increased morbidity and mortality. It occurs in 9%-44% of cardiac surgery patients after cardiopulmonary bypass (CPB). The underlying pathophysiology following CPB consists of resistance to vasopressors (inactivation of Ca voltage gated channels) on the one hand and excessive activation of vasodilators (SIRS, iNOS, and low AVP) on the other. Use of angiotensin-converting enzyme inhibitor (ACE-I), calcium channel blockers, amiodarone, heparin, low cardiac reserve (EF < 35%), symptomatic congestive heart failure, and diabetes mellitus are the perioperative risk factors for VPS after cardiac surgery in adults. Till date, there is no consensus about the outcome-oriented therapeutic management of VPS. Vasopressors such as norepinephrine (NE; 0.025-0.2 µg/kg/min) and vasopressin (0.06 U/min or 6 U/h median dose) are the first choice for the treatment. The adjuvant therapy (hydrocortisone, calcium, vitamin C, and thiamine) and rescue therapy (methylene blue [MB] and hydroxocobalamin) are also considered when perfusion goals (meanarterial pressure [MAP] > 60-70 mmHg) are not achieved with nor-epinephrine and/or vasopressin.
AIMS
The aims of this systematic review are to collect all the clinically relevant data to describe the VPS, its potential risk factors, pathophysiology after CPB, and to assess the efficacy, safety, and outcome of the therapeutic management with catecholamine and non-catecholamine vasopressors employed for refractory vasoplegia after cardiac surgery. Also, to elucidate the current and practical approach for management of VPS after cardiac surgery.
MATERIAL AND METHODS
"PubMed," "Google," and "Medline" weresearched, and over 150 recent relevant articles including RCTs, clinical studies, meta-analysis, reviews, case reports, case series and Cochrane data were analyzed for this systematic review. The filter was applied specificallyusing key words like VPS after cardiac surgery, perioperative VPS following CPB, morbidity, and mortality in VPS after cardiac surgery, vasopressors for VPS that improve outcomes, VPS after valve surgery, VPS after CABG surgery, VPS following complex congenital cardiac anomalies corrective surgery, rescue therapy for VPS, adjuvant therapy for VPS, definition of VPS, outcome in VPS after cardiac surgery, etiopathology of VPS following CPB. This review did not require any ethical approval or consent from the patients.
RESULTS
Despite the recent advances in therapy, the mortality remains as high as 30%-50%. NE has been recommended the most frequent used vasopressor for VPS. It restores and maintain the MAP and provides the outcome benefits. Vasopressin rescue therapy is an alternative approach, if catecholamines and fluid infusions fail to improve hemodynamics. It effectively increases vascular tone and lowers CO, and significantly decreases the 30 days mortality. Hence, suggested a first-line vasopressor agent in postcardiac surgery VPS. Terlipressin (1.3μg/kg/h), a longer acting and more specific vasoconstrictor prevents the development of VPS after CPB in patients treated with ACE-I. MB significantly reduces morbidity and mortality of VPS. The Preoperative MB (1%, 2mg/kg/30min, 1h before surgery) administration in high risk (on ACE-I) patients for VPS undergoing CABG surgery, provides 100% protection against VPS, and early of MB significantly reduces operative mortality, and recommended as a rescue therapy for VPS. Hydroxocobalamin (5 g) has been recommended as a rescue agent in VPS refractory to multiple vasopressors. A combination of ascorbic acid (6 g), hydrocortisone (200 mg/day), and thiamine (400 mg/day) as an adjuvant therapy significantly reduces the vasopressors requirement, and provides mortality and morbidity benefits.
CONCLUSION
Currently, the VPS is frequently encountered (9%-40%) in cardiac surgical patients with predisposing patient-specific risk factors and combined with inflammatory response to CPB. Multidrug therapy (NE, MB, AVP, ATII, terlipressin, hydroxocobalamin) targeting multiple receptor systems is recommended in refractory VPS. A combination of high dosage of ascorbic acid, hydrocortisone and thiamine has been used successfully as adjunctive therapyto restore the MAP. We also advocate for the early use of multiagent vasopressors therapy and catecholamine sparing adjunctive agents to restore the systemic perfusion pressure with a goal of preventing the progressive refractory VPS.
Topics: Adult; Cardiopulmonary Bypass; Drug Therapy, Combination; Humans; Hydroxocobalamin; Leprostatic Agents; Vasoplegia
PubMed: 34251716
DOI: 10.1111/jocs.15805 -
Current Cardiology Reviews 2022Junctional Ectopic Tachycardia (JET) is an arrhythmia originating from the AV junction, which may occur following congenital heart surgery, especially when the... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Junctional Ectopic Tachycardia (JET) is an arrhythmia originating from the AV junction, which may occur following congenital heart surgery, especially when the intervention is near the atrioventricular junction.
OBJECTIVE
The aim of this systematic review and meta-analysis is to compare the effectiveness of amiodarone, dexmedetomidine, and magnesium in preventing JET following congenital heart surgery.
METHODS
This meta-analysis was conducted according to the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) statement, where 11 electronic databases were searched from the date of inception to August 2020. The incidence of JET was calculated with the relative risk of 95% Confidence Interval (CI). Quality assessment of the included studies was assessed using the Consolidated Standards of Reporting Trials (CONSORT) 2010 statement.
RESULTS
Eleven studies met the predetermined inclusion criteria and were included in this meta-analysis. Amiodarone, dexmedetomidine, and magnesium significantly reduced the incidence of postoperative JET [Amiodarone: risk ratio 0.34; I2= 0%; Z=3.66 (P=0.0002); 95% CI 0.19-0.60. Dexmedetomidine: risk ratio 0.34; I2= 0%; Z=4.77 (P<0.00001); 95% CI 0.21-0.52. Magnesium: risk ratio 0.50; I2= 24%; Z=5.08 (P<0.00001); 95% CI 0.39-0.66].
CONCLUSION
All three drugs have shown promising results in reducing the incidence of JET. Our systematic review found that dexmedetomidine is better in reducing the length of ICU stays as well as mortality. In addition, dexmedetomidine also has the least pronounced side effects among the three. However, it should be noted that this conclusion was derived from studies with small sample sizes. Therefore, dexmedetomidine may be considered as the drug of choice for preventing JET.
Topics: Cardiac Surgical Procedures; Dexmedetomidine; Humans; Postoperative Complications; Tachycardia, Ectopic Junctional
PubMed: 34082685
DOI: 10.2174/1573403X17666210603113430 -
The Journal of Heart and Lung... Jul 2021Primary graft dysfunction (PGD) is a leading cause of early mortality after heart transplant (HTx). To identify PGD incidence and impact on mortality, and to elucidate... (Meta-Analysis)
Meta-Analysis
PURPOSE
Primary graft dysfunction (PGD) is a leading cause of early mortality after heart transplant (HTx). To identify PGD incidence and impact on mortality, and to elucidate risk factors for PGD, we systematically reviewed studies using the ISHLT 2014 Consensus Report definition and reporting the incidence of PGD in adult HTx recipients.
METHODS
We conducted a systematic search in January 2020 including studies reporting the incidence of PGD in adult HTx recipients. We used a random effects model to pool the incidence of PGD among HTx recipients and, for each PGD severity, the mortality rate among those who developed PGD. For prognostic factors evaluated in ≥2 studies, we used random effects meta-analyses to pool the adjusted odds ratios for development of PGD. The GRADE framework informed our certainty in the evidence.
RESULTS
Of 148 publications identified, 36 observational studies proved eligible. With moderate certainty, we observed pooled incidences of 3.5%, 6.6%, 7.7%, and 1.6% and 1-year mortality rates of 15%, 21%, 41%, and 35% for mild, moderate, severe and isolated right ventricular-PGD, respectively. Donor factors (female sex, and undersized), recipient factors (creatinine, and pre-HTx use of amiodarone, and temporary or durable mechanical support), and prolonged ischemic time proved associated with PGD post-HTx.
CONCLUSION
Our review suggests that the incidence of PGD may be low but its risk of mortality high, increasing with PGD severity. Prognostic factors, including undersized donor, recipient use of amiodarone pre-HTx and recipient creatinine may guide future studies in exploring donor and/or recipient selection and risk mitigation strategies.
Topics: Global Health; Heart Failure; Heart Transplantation; Humans; Incidence; Primary Graft Dysfunction; Risk Factors; Tissue Donors; Transplant Recipients
PubMed: 33947602
DOI: 10.1016/j.healun.2021.03.015 -
Europace : European Pacing,... Aug 2021Single oral dose anti-arrhythmic drugs (AADs) are used to cardiovert recent-onset atrial fibrillation (AF); however, the optimal agent is uncertain. (Meta-Analysis)
Meta-Analysis
Single-dose oral anti-arrhythmic drugs for cardioversion of recent-onset atrial fibrillation: a systematic review and network meta-analysis of randomized controlled trials.
AIMS
Single oral dose anti-arrhythmic drugs (AADs) are used to cardiovert recent-onset atrial fibrillation (AF); however, the optimal agent is uncertain.
METHODS
We performed a systematic review and network meta-analysis of randomized trials testing single oral dose AADs vs. any comparator to cardiovert AF <7 days duration. We searched MEDLINE, Embase, and CENTRAL to April 2020. The primary outcome was successful cardioversion at timepoint nearest 8 h after administration.
RESULTS
From 12 712 citations, 22 trials (2320 patients) were included. Thirteen trials included patients with some degree of heart failure; 19 included patients with some degree of ischaemic heart disease vs. placebo or rate-control (32% success) at 8 h, flecainide [73%, network odds ratio (OR) 7.6, 95% credible interval (CrI) 4.4-14.0], propafenone (70%, OR 4.6, CrI 2.9-7.3), and pilsicainide (59%, OR 10.0, CrI 1.8-69.0), but not amiodarone (28%, OR 1.0, CrI 0.4-2.8) were superior. Flecainide (OR 7.5, CrI 2.6-24.0) and propafenone (OR 4.5, CrI 1.6-13.0) were superior to amiodarone; propafenone vs. flecainide did not statistically differ (OR 0.6, CrI 0.3-1.1). At longest follow-up, amiodarone was superior to placebo (OR 11.0, CrI 3.2-41.0), flecainide vs. amiodarone (OR 0.79, CrI 0.19-3.1), and propafenone vs. amiodarone (OR 0.36, CrI 0.092-1.4) were not statistically different, and flecainide was superior to propafenone (OR 2.2, CrI 1.1-4.8). Atrial and ventricular tachyarrhythmias, bradyarrhythmias, and hypotension were rare with PO AADs.
CONCLUSION
Single oral dose Class 1C AADs are effective and safe for cardioversion of recent-onset AF. Flecainide may be superior to propafenone. Amiodarone is a slower acting alternative.
Topics: Amiodarone; Anti-Arrhythmia Agents; Atrial Fibrillation; Electric Countershock; Humans; Network Meta-Analysis; Pharmaceutical Preparations; Propafenone; Randomized Controlled Trials as Topic
PubMed: 33723602
DOI: 10.1093/europace/euab014 -
JACC. Clinical Electrophysiology Jan 2021The authors performed a systematic review and meta-analysis to determine the efficacy of renal denervation (RDN) in patients with refractory ventricular arrhythmias (VA)... (Meta-Analysis)
Meta-Analysis
OBJECTIVES
The authors performed a systematic review and meta-analysis to determine the efficacy of renal denervation (RDN) in patients with refractory ventricular arrhythmias (VA) or electrical storm (ES).
BACKGROUND
Although catheter ablation is efficacious for the treatment of structural heart disease ventricular tachycardia (VT), there are proportion of patients who have refractory VT despite multiple procedures. In this setting, novel adjunctive therapies such as renal denervation have been performed.
METHODS
A systematic review of published data was performed. Studies that evaluated patients undergoing RDN for VA or ES were included. Outcome measures of VA, sudden cardiac death, ES, or device therapy were required. Case reports, editorials, and conference presentations were excluded. Random effects meta-analysis was conducted to explore change or final mean values in the study outcomes.
RESULTS
A total of 328 articles were identified by the literature search. Seven studies met the eligibility criteria and were included in the systematic review, with a total of 121 pooled patients. The weighted mean age was 63.8 ± 13.1 years, ejection fraction 30.5 ± 10.3%, 76% were men, 99% were on a beta blocker, 79% were on amiodarone, 46% had previously undergone catheter ablation, and 8.3% had previously undergone cardiac sympathetic denervation. Meta-analysis demonstrated a significant effect of RDN in reducing implantable cardiac defibrillator therapies, with a standardized mean difference (SMD) of -3.11 (p < 0.001). RDN also reduced the number of VA episodes (SMD -2.13; p < 0.001), antitachycardia pacing episodes (SMD -2.82; p = 0.002), and shocks (SMD -2.82; p = 0.002).
CONCLUSIONS
RDN is an effective treatment for refractory VAs and ES, although randomized data are lacking.
Topics: Arrhythmias, Cardiac; Defibrillators, Implantable; Humans; Kidney; Male; Middle Aged; Sympathectomy; Tachycardia, Ventricular
PubMed: 33478701
DOI: 10.1016/j.jacep.2020.07.019 -
CJC Open Jan 2021Observational studies have identified inconsistent associations between chronic use of amiodarone and cancer-related outcomes. We performed a systematic review and... (Review)
Review
BACKGROUND
Observational studies have identified inconsistent associations between chronic use of amiodarone and cancer-related outcomes. We performed a systematic review and meta-analysis to evaluate cancer risk among patients receiving amiodarone.
METHODS
We searched MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials (CENTRAL) to May 1, 2020. We included randomized controlled trials (RCTs) with follow-up ≥2 years that compared amiodarone (any dose) to any comparator (placebo, active pharmacologic or interventional comparator, or usual care), and reported ≥1 outcome of interest. We contacted authors of published chronic amiodarone trials for potentially unreported cancer outcomes. The primary outcome was cancer incidence. Secondary outcomes were cancer-related death and site-specific cancers. We determined risk ratios and 95% confidence intervals using a fixed-effect model, and statistical heterogeneity using . We conducted prespecified subgroup and sensitivity analyses for amiodarone indication, amiodarone dose, duration of therapy, and trial-level risk of bias.
RESULTS
From 1439 articles, we included 5 RCTs (n = 4357). Mean follow-up duration ranged from 21 to 37 months. We included previously unpublished cancer outcome data from 1 RCT. Our primary outcome was not reported in any RCT. There was no significant difference in cancer-related death between amiodarone (1.69%) and the comparator (1.75%) (risk ratio 0.96, 95% confidence interval 0.57-1.63; = 0%). There were no significant interactions from our subgroup or sensitivity analyses.
CONCLUSIONS
Chronic amiodarone use did not increase cancer-related deaths. Data from RCTs do not support an increased risk of cancer-related harms with amiodarone use, and these concerns should not deter use of amiodarone when indicated.
PubMed: 33458637
DOI: 10.1016/j.cjco.2020.09.013 -
Cardiovascular Drugs and Therapy Apr 2021We sought to indirectly compare and rank antiarrhythmic agents focusing exclusively on adults with paroxysmal atrial fibrillation in order to identify the most effective... (Meta-Analysis)
Meta-Analysis
PURPOSE
We sought to indirectly compare and rank antiarrhythmic agents focusing exclusively on adults with paroxysmal atrial fibrillation in order to identify the most effective for pharmacologic cardioversion over different time settings (4 h as primary, and 12, 24 h as secondary outcomes).
METHODS
We searched several databases from inception to March 2020 without language restrictions, ClinicalTrials.gov, references of reviews, and meeting abstract material. We included randomized controlled trials of patients with AF lasting ≤7 days comparing either two or more intravenous (i.v.) or oral (p.o.) pharmacologic cardioversion agents or an agent against placebo. For each outcome, we performed network meta-analysis based on the frequentist approach.
RESULTS
Forty-one trials (6013 patients) were included in our systematic review. Moderate confidence evidence suggests that i.v. vernakalant and flecainide have the highest conversion rate within 4 h, possibly allowing discharge from the emergency department and reducing hospital admissions. Intravenous and p.o. formulations of class IC antiarrhythmics (flecainide more so than propafenone) are superior regarding conversion rates within 12 h, while amiodarone efficacy is exhibited in a delayed fashion (within 24 h), especially if ranolazine is added.
CONCLUSION
Our network meta-analysis identified with sufficient power and consistency the most effective antiarrhythmics for pharmacologic cardioversion over different time settings, with vernakalant and flecainide exhibiting a safer and more efficacious profile toward faster cardioversion.
Topics: Anisoles; Anti-Arrhythmia Agents; Atrial Fibrillation; Flecainide; Humans; Pyrrolidines; Randomized Controlled Trials as Topic
PubMed: 33400054
DOI: 10.1007/s10557-020-07127-1 -
Thrombosis Research Oct 2020Direct oral anticoagulants (DOACs) have emerged as safe and effective alternatives to Vitamin-K antagonists for treatment and prevention of arterial and venous... (Review)
Review
BACKGROUND
Direct oral anticoagulants (DOACs) have emerged as safe and effective alternatives to Vitamin-K antagonists for treatment and prevention of arterial and venous thrombosis. Due to their novelty, pharmacokinetic DOAC drug-drug interactions (DDIs) that result in clinical adverse events have not been well-documented.
OBJECTIVE
This study aims to systematically review reported pharmacokinetic DDIs resulting in clinical adverse events through documented observational evidence to better inform clinicians in clinical practice.
METHODS
A comprehensive literature review of EMBASE, MEDLINE, and Ovid HealthStar was conducted through March 10th, 2020. Two independent reviewers screened and extracted data from eligible articles according to pre-established inclusion and exclusion criteria. Articles reporting bleeding or thrombotic outcomes in non-controlled (observational) settings resulting from suggested pharmacokinetic DOAC DDIs were included.
RESULTS
A total of 5567 citations were reviewed, of which 24 were included following data extraction. The majority were case reports (n = 21) documenting a single adverse event resulting from a suspected DOAC DDI, while the remaining papers were a case series (n = 1) and cohort studies (n = 2). The most commonly reported interacting drugs were amiodarone and ritonavir (bleeding), and phenobarbital, phenytoin, and carbamazepine (thrombosis). Bleeding events more often resulted from a combined mechanism (P-glycoprotein AND CYP3A4 inhibition), whereas thrombotic events resulted from either combined OR single P-glycoprotein/CYP3A4 induction.
CONCLUSION
Current literature evaluating the real-world risk of DOAC DDIs is limited to few case reports and retrospective observational analyses. Clinicians are encouraged to continue to report suspected drug interactions resulting in adverse events.
Topics: Administration, Oral; Anticoagulants; Drug Interactions; Hemorrhage; Humans; Observational Studies as Topic; Pharmaceutical Preparations; Retrospective Studies
PubMed: 33213849
DOI: 10.1016/j.thromres.2020.08.016