-
Journal of the American Heart... Dec 2017There 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)
Meta-Analysis Review
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; I=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; I=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; I=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; I=0%). There was no difference in fetal demise between flecainide and digoxin (OR: 0.767; 95% CI, 0.140-4.197; I=44%).
CONCLUSIONS
Flecainide may be more effective treatment than digoxin as a first-line treatment for fetal supraventricular tachycardia.
Topics: Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Echocardiography; Female; Fetal Diseases; Fetal Therapies; Flecainide; Humans; Pregnancy; Prenatal Care; Prenatal Diagnosis
PubMed: 29246961
DOI: 10.1161/JAHA.117.007164 -
Kardiologia Polska Oct 2020Appropriate pharmacotherapy during advanced resuscitation procedures may affect the return of spontaneous circulation. Current guidelines on cardiopulmonary... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Appropriate pharmacotherapy during advanced resuscitation procedures may affect the return of spontaneous circulation. Current guidelines on cardiopulmonary resuscitation recommend amiodarone for shock‑refractory cardiac arrest or when lidocaine is not available.
AIMS
The aim of this study was to systematically analyze the available literature and to conduct a meta‑‑analysis to determine the effect of amiodarone and lidocaine on survival and neurological outcome after shock‑refractory cardiac arrest.
METHODS
PubMed, Scopus, Embase, Web of Science, and Cochrane Library databases were searched. Two independent reviewers screened randomized and quasi‑randomized controlled trials as well as cohort and cross‑sectional trials evaluating amiodarone or lidocaine for the treatment of adults with cardiac arrest.
RESULTS
After screening 682 unique references, 8 were selected for this meta‑analysis. A higher number of cases with return of spontaneous circulation was observed in the amiodarone group compared with the lidocaine group (OR, 1.03; 95% CI, 0.87-1.21; P = 0.75). A similar relationship was observed for survival to hospital discharge (OR, 1.12; 95% CI, 0.92-1.38; P = 0.26), as well as survival with favorable neurological outcome (OR, 1.11; 95% CI, 0.89-1.39; P = 0.35).
CONCLUSIONS
We found no statistically significant survival benefit of resuscitation with amiodarone compared with lidocaine. Future randomized controlled trials are needed to identify which antiarrhythmic drug should be use in shock‑refractory cardiac arrest.
Topics: Amiodarone; Anti-Arrhythmia Agents; Cardiopulmonary Resuscitation; Cross-Sectional Studies; Humans; Lidocaine; Out-of-Hospital Cardiac Arrest
PubMed: 32627999
DOI: 10.33963/KP.15483 -
British Journal of Anaesthesia May 2022New onset atrial fibrillation (NOAF) is the most common arrhythmia affecting critically unwell patients. NOAF can lead to worsening haemodynamic compromise, heart... (Review)
Review
BACKGROUND
New onset atrial fibrillation (NOAF) is the most common arrhythmia affecting critically unwell patients. NOAF can lead to worsening haemodynamic compromise, heart failure, thromboembolic events, and increased mortality. The aim of this systematic review and narrative synthesis is to evaluate the non-pharmacological and pharmacological management strategies for NOAF in critically unwell patients.
METHODS
Of 1782 studies, 30 were eligible for inclusion, including 4 RCTs and 26 observational studies. Efficacy of direct current cardioversion, amiodarone, β-adrenergic receptor antagonists, calcium channel blockers, digoxin, magnesium, and less commonly used agents such as ibutilide are reported.
RESULTS
Cardioversion rates of 48% were reported for direct current cardioversion; however, re-initiation of NOAF was as high as 23.4%. Amiodarone was the most commonly reported intervention with cardioversion rates ranging from 18% to 96% followed by β-antagonists with cardioversion rates from 40% to 92%. Amiodarone was more effective than diltiazem (odds ratio [OR]=1.91, P=0.32) at cardioversion. Short-acting β-antagonists esmolol and landiolol were more effective compared with diltiazem for cardioversion (OR=3.55, P=0.04) and HR control (OR=3.2, P<0.001).
CONCLUSION
There was significant variation between studies with regard to the definition of successful cardioversion and heart rate control, making comparisons between studies and interventions difficult. Future RCTs comparing individual anti-arrhythmic agents, in particular magnesium, amiodarone, and β-antagonists, and studying the role of anticoagulation in critically unwell patients are required. There is also an urgent need for a core outcome dataset for studies of new onset atrial fibrillation to allow comparisons between different anti-arrhythmic strategies.
CLINICAL TRIAL REGISTRATION
PROSPERO CRD42019121739.
Topics: Adult; Amiodarone; Anti-Arrhythmia Agents; Atrial Fibrillation; Diltiazem; Electric Countershock; Humans; Magnesium
PubMed: 34916053
DOI: 10.1016/j.bja.2021.11.016 -
JACC. Clinical Electrophysiology Jun 2023There is variability in treatment modalities for premature ventricular complexes (PVCs), including use of antiarrhythmic drug (AAD) therapy or catheter ablation (CA).... (Review)
Review
There is variability in treatment modalities for premature ventricular complexes (PVCs), including use of antiarrhythmic drug (AAD) therapy or catheter ablation (CA). This study reviewed evidence comparing CA vs AADs for the treatment of PVCs. A systematic review was performed from the Medline, Embase, and Cochrane Library databases, as well as the Australian and New Zealand Clinical Trials Registry, U.S. National Library of Medicine ClinicalTrials database, and the European Union Clinical Trials Register. Five studies (1 randomized controlled trial) enrolling 1,113 patients (57.9% female) were analyzed. Four of five studies recruited mainly patients with outflow tract PVCs. There was significant heterogeneity in AAD choice. Electroanatomic mapping was used in 3 of 5 studies. No studies documented intracardiac echocardiography or contact force-sensing catheter use. Acute procedural endpoints varied (2 of 5 targeted elimination of all PVCs). All studies had significant potential for bias. CA seemed superior to AADs for PVC recurrence, frequency, and burden. One study reported long-term symptoms (CA superior). Quality of life or cost-effectiveness was not reported. Complication and adverse event rates were 0% to 5.6% for CA and 9.5% to 21% for AADs. Future randomized controlled trials will assess CA vs AADs for patients with PVCs without structural heart disease (ECTOPIA [Elimination of Ventricular Premature Beats with Catheter Ablation versus Optimal Antiarrhythmic Drug Treatment]), with impaired LVEF (PAPS [Prospective Assessment of Premature Ventricular Contractions Suppression in Cardiomyopathy] Pilot), and with structural heart disease (CAT-PVC [Catheter Ablation Versus Amiodarone for Therapy of Premature Ventricular Contractions in Patients With Structural Heart Disease]). In conclusion, CA seems to reduce recurrence, burden, and frequency of PVCs compared with AADs. There is a lack of data on patient- and health care-specific outcomes such as symptoms, quality of life, and cost-effectiveness. Several upcoming trials will offer important insights for management of PVCs.
Topics: Female; United States; Male; Humans; Anti-Arrhythmia Agents; Prospective Studies; Quality of Life; Ventricular Premature Complexes; Australia; Heart Diseases; Catheter Ablation
PubMed: 37380322
DOI: 10.1016/j.jacep.2023.01.035 -
Clinical Toxicology (Philadelphia, Pa.) Sep 2018While pulmonary arterial hypertension remains an uncommon diagnosis, various therapeutic agents are recognized as important associations. These agents are typically...
INTRODUCTION
While pulmonary arterial hypertension remains an uncommon diagnosis, various therapeutic agents are recognized as important associations. These agents are typically categorized into "definite", "likely", "possible", or "unlikely" to cause pulmonary arterial hypertension, based on the strength of evidence.
OBJECTIVE
This review will focus on those therapeutic agents where there is sufficient literature to adequately comment on the role of the agent in the pathogenesis of pulmonary arterial hypertension.
METHODS
A systematic search was conducted using PubMed covering the period September 1970- 2017. The search term utilized was "drug induced pulmonary hypertension". This resulted in the identification of 853 peer-reviewed articles including case reports. Each paper was then reviewed by the authors for its relevance. The majority of these papers (599) were excluded as they related to systemic hypertension, chronic obstructive pulmonary disease, human immunodeficiency virus, pulmonary fibrosis, alternate differential diagnosis, treatment, basic science, adverse effects of treatment, and pulmonary hypertension secondary to pulmonary embolism. Agents affecting serotonin metabolism (and related anorexigens): Anorexigens, such as aminorex, fenfluramine, benfluorex, phenylpropanolamine, and dexfenfluramine were the first class of medications recognized to cause pulmonary arterial hypertension. Although most of these medications have now been withdrawn worldwide, they remain important not only from a historical perspective, but because their impact on serotonin metabolism remains relevant. Selective serotonin reuptake inhibitors, tryptophan, and lithium, which affect serotonin metabolism, have also been implicated in the development of pulmonary arterial hypertension. Interferon and related medications: Interferon alfa and sofosbuvir have been linked to the development of pulmonary arterial hypertension in patients with other risk factors, such as human immunodeficiency virus co-infection. Antiviral therapies: Sofosbuvir has been associated with two cases of pulmonary artery hypertension in patients with multiple risk factors for its development. Its role in pathogenesis remains unclear. Small molecule tyrosine kinase inhibitors: Small molecule tyrosine kinase inhibitors represent a relatively new class of medications. Of these dasatinib has the strongest evidence in drug-induced pulmonary arterial hypertension, considered a recognized cause. Nilotinib, ponatinib, carfilzomib, and ruxolitinib are newer agents, which paradoxically have been linked to both cause and treatment for pulmonary arterial hypertension. Monoclonal antibodies and immune regulating medications: Several case reports have linked some monoclonal antibodies and immune modulating therapies to pulmonary arterial hypertension. There are no large series documenting an increased prevalence of pulmonary arterial hypertension complicating these agents; nonetheless, trastuzumab emtansine, rituximab, bevacizumab, cyclosporine, and leflunomide have all been implicated in case reports. Opioids and substances of abuse: Buprenorphine and cocaine have been identified as potential causes of pulmonary arterial hypertension. The mechanism by which this occurs is unclear. Tramadol has been demonstrated to cause severe, transient, and reversible pulmonary hypertension. Chemotherapeutic agents: Alkylating and alkylating-like agents, such as bleomycin, cyclophosphamide, and mitomycin have increased the risk of pulmonary veno-occlusive disease, which may be clinically indistinct from pulmonary arterial hypertension. Thalidomide and paclitaxel have also been implicated as potential causes. Miscellaneous medications: Protamine appears to be able to cause acute, reversible pulmonary hypertension when bound to heparin. Amiodarone is also capable of causing pulmonary hypertension by way of recognized side effects.
CONCLUSIONS
Pulmonary arterial hypertension remains a rare diagnosis, with drug-induced causes even more uncommon, accounting for only 10.5% of cases in large registry series. Despite several agents being implicated in the development of PAH, the supportive evidence is typically limited, based on case series and observational data. Furthermore, even in the drugs with relatively strong associations, factors that predispose an individual to PAH have yet to be elucidated.
Topics: Drug-Related Side Effects and Adverse Reactions; Humans; Hypertension, Pulmonary; Muscle, Smooth, Vascular; Prescription Drugs
PubMed: 29508628
DOI: 10.1080/15563650.2018.1447119 -
The Cochrane Database of Systematic... Aug 2015Coronary artery disease is a major public health problem affecting both developed and developing countries. Acute coronary syndromes include unstable angina and... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Coronary artery disease is a major public health problem affecting both developed and developing countries. Acute coronary syndromes include unstable angina and myocardial infarction with or without ST-segment elevation (electrocardiogram sector is higher than baseline). Ventricular arrhythmia after myocardial infarction is associated with high risk of mortality. The evidence is out of date, and considerable uncertainty remains about the effects of prophylactic use of lidocaine on all-cause mortality, in particular, in patients with suspected myocardial infarction.
OBJECTIVES
To determine the clinical effectiveness and safety of prophylactic lidocaine in preventing death among people with myocardial infarction.
SEARCH METHODS
We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (2015, Issue 3), MEDLINE Ovid (1946 to 13 April 2015), EMBASE (1947 to 13 April 2015) and Latin American Caribbean Health Sciences Literature (LILACS) (1986 to 13 April 2015). We also searched Web of Science (1970 to 13 April 2013) and handsearched the reference lists of included papers. We applied no language restriction in the search.
SELECTION CRITERIA
We included randomised controlled trials assessing the effects of prophylactic lidocaine for myocardial infarction. We considered all-cause mortality, cardiac mortality and overall survival at 30 days after myocardial infarction as primary outcomes.
DATA COLLECTION AND ANALYSIS
We performed study selection, risk of bias assessment and data extraction in duplicate. We estimated risk ratios (RRs) for dichotomous outcomes and measured statistical heterogeneity using I(2). We used a random-effects model and conducted trial sequential analysis.
MAIN RESULTS
We identified 37 randomised controlled trials involving 11,948 participants. These trials compared lidocaine versus placebo or no intervention, disopyramide, mexiletine, tocainide, propafenone, amiodarone, dimethylammonium chloride, aprindine and pirmenol. Overall, trials were underpowered and had high risk of bias. Ninety-seven per cent of trials (36/37) were conducted without an a priori sample size estimation. Ten trials were sponsored by the pharmaceutical industry. Trials were conducted in 17 countries, and intravenous intervention was the most frequent route of administration.In trials involving participants with proven or non-proven acute myocardial infarction, lidocaine versus placebo or no intervention showed no significant differences regarding all-cause mortality (213/5879 (3.62%) vs 199/5848 (3.40%); RR 1.02, 95% CI 0.82 to 1.27; participants = 11727; studies = 18; I(2) = 15%); low-quality evidence), cardiac mortality (69/4184 (1.65%) vs 62/4093 (1.51%); RR 1.03, 95% CI 0.70 to 1.50; participants = 8277; studies = 12; I(2) = 12%; low-quality evidence) and prophylaxis of ventricular fibrillation (76/5128 (1.48%) vs 103/4987 (2.01%); RR 0.78, 95% CI 0.55 to 1.12; participants = 10115; studies = 16; I(2) = 18%; low-quality evidence). In terms of sinus bradycardia, lidocaine effect is imprecise compared with effects of placebo or no intervention (55/1346 (4.08%) vs 49/1203 (4.07%); RR 1.09, 95% CI 0.66 to 1.80; participants = 2549; studies = 8; I(2) = 21%; very low-quality evidence). In trials involving only participants with proven acute myocardial infarction, lidocaine versus placebo or no intervention showed no significant differences in all-cause mortality (148/2747 (5.39%) vs 135/2506 (5.39%); RR 1.01, 95% CI 0.79 to 1.30; participants = 5253; studies = 16; I(2) = 9%; low-quality evidence). No significant differences were noted between lidocaine and any other antiarrhythmic drug in terms of all-cause mortality and ventricular fibrillation. Data on overall survival 30 days after myocardial infarction were not reported. Lidocaine compared with placebo or no intervention increased risk of asystole (35/3393 (1.03%) vs 14/3443 (0.41%); RR 2.32, 95% CI 1.26 to 4.26; participants = 6826; studies = 4; I(2) = 0%; very low-quality evidence) and dizziness/drowsiness (74/1259 (5.88%) vs 16/1274 (1.26%); RR 3.85, 95% CI 2.29 to 6.47; participants = 2533; studies = 6; I(2) = 0%; low-quality evidence). Overall, safety data were poorly reported and adverse events may have been underestimated. Trial sequential analyses suggest that additional trials may not be needed for reliable conclusions to be drawn regarding these outcomes.
AUTHORS' CONCLUSIONS
This Cochrane review found evidence of low quality to suggest that prophylactic lidocaine has very little or no effect on mortality or ventricular fibrillation in people with acute myocardial infarction. The safety profile is unclear. This conclusion is based on randomised controlled trials with high risk of bias. However (disregarding the risk of bias), trial sequential analysis suggests that additional trials may not be needed to disprove an intervention effect of 20% relative risk reduction. Smaller risk reductions might require additional higher trials.
Topics: Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Bradycardia; Humans; Lidocaine; Myocardial Infarction; Randomized Controlled Trials as Topic; Ventricular Fibrillation
PubMed: 26295202
DOI: 10.1002/14651858.CD008553.pub2 -
Critical Care Nurse Feb 2019Intravenous amiodarone is the gold-standard treatment for arrhythmias, but phlebitis is a common adverse effect.
BACKGROUND
Intravenous amiodarone is the gold-standard treatment for arrhythmias, but phlebitis is a common adverse effect.
OBJECTIVES
To determine the incidence and contributing factors of amiodarone-induced phlebitis and examine phlebitis severity.
METHODS
A systematic review was conducted of articles published before February 2016 in the Cumulative Index to Nursing and Allied Health Literature, Cochrane Library, MEDLINE, Embase, Web of Science, and gray databases (Bielefeld, Lenus, EUGrey, RIAN, and DART). All studies in which amiodarone-induced phlebitis was a primary or secondary outcome were included. Meta-analysis was not appropriate because of study heterogeneity. Studies of the same contributing factors were analyzed together.
RESULTS
In the 20 included studies, phlebitis incidence ranged from 0% to 85%. Increasing the infusion concentration from 1.2 mg/mL to 1.8 mg/mL increased the phlebitis rate ( < .001). Total amiodarone doses greater than 1 g resulted in higher phlebitis rates than did doses less than 0.45 mg ( < .001). Most infusion durations and rates were not correlated with phlebitis incidence. However, phlebitis incidence was lower with bolus administration than with longer infusions ( = .002). The use of in-line filters and nursing guidelines significantly reduced phlebitis rates ( < .001) and phlebitis severity. The most common phlebitis severity grades, in descending order, were 0, 1, 2, 3, and 4.
CONCLUSIONS
Understanding factors that increase the risk of amiodarone-induced phlebitis can guide better practice. In-line filters and nursing guidelines should always be implemented when administering intravenous amiodarone. Increased surveillance is required when higher dosages and concentrations are used.
Topics: Amiodarone; Anti-Arrhythmia Agents; Humans; Incidence; Infusions, Intravenous; Phlebitis; Severity of Illness Index
PubMed: 30710042
DOI: 10.4037/ccn2019381 -
PLoS Neglected Tropical Diseases Aug 2018Chagas disease is a neglected chronic condition caused by Trypanosoma cruzi, with high prevalence and burden in Latin America. Ventricular arrhythmias are common in... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Chagas disease is a neglected chronic condition caused by Trypanosoma cruzi, with high prevalence and burden in Latin America. Ventricular arrhythmias are common in patients with Chagas cardiomyopathy, and amiodarone has been widely used for this purpose. The aim of our study was to assess the effect of amiodarone in patients with Chagas cardiomyopathy.
METHODOLOGY
We searched MEDLINE, Embase and LILACS up to January 2018. Data from randomized and observational studies evaluating amiodarone use in Chagas cardiomyopathy were included. Two reviewers selected the studies, extracted data and assessed risk of bias. Overall quality of evidence was accessed using Grading of Recommendations Assessment, Development and Evaluation (GRADE).
PRINCIPAL FINDINGS
We included 9 studies (3 before-after studies, 5 case series and 1 randomized controlled trial). Two studies with a total of 38 patients had the full dataset, allowing individual patient data (IPD) analysis. In 24-hour Holter, amiodarone reduced the number of ventricular tachycardia episodes in 99.9% (95%CI 99.8%-100%), ventricular premature beats in 93.1% (95%CI 82%-97.4%) and the incidence of ventricular couplets in 79% (RR 0.21, 95%CI 0.11-0.39). Studies not included in the IPD analysis showed a reduction of ventricular premature beats (5 studies), ventricular tachycardia (6 studies) and ventricular couplets (1 study). We pooled the incidence of adverse side effects with random effects meta-analysis; amiodarone was associated with corneal microdeposits (61.1%, 95%CI 19.0-91.3, 5 studies), gastrointestinal events (16.1%, 95%CI 6.61-34.2, 3 studies), sinus bradycardia (12.7%, 95%CI 3.71-35.5, 6 studies), dermatological events (10.6%, 95%CI 4.77-21.9, 3 studies) and drug discontinuation (7.68%, 95%CI 4.17-13.7, 5 studies). Quality of evidence ranged from moderate to very low.
CONCLUSIONS
Amiodarone is effective in reducing ventricular arrhythmias, but there is no evidence for hard endpoints (sudden death, hospitalization). Although our findings support the use of amiodarone, it is important to balance the potential benefits and harms at the individual level for decision-making.
Topics: Amiodarone; Arrhythmias, Cardiac; Chagas Cardiomyopathy
PubMed: 30125291
DOI: 10.1371/journal.pntd.0006742 -
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 -
PloS One 2018During recent years, systematic reviews of observational studies have compared digoxin to no digoxin in patients with atrial fibrillation or atrial flutter, and the... (Comparative Study)
Comparative Study Meta-Analysis Review
BACKGROUND
During recent years, systematic reviews of observational studies have compared digoxin to no digoxin in patients with atrial fibrillation or atrial flutter, and the results of these reviews suggested that digoxin seems to increase the risk of all-cause mortality regardless of concomitant heart failure. Our objective was to assess the benefits and harms of digoxin for atrial fibrillation and atrial flutter based on randomized clinical trials.
METHODS
We searched CENTRAL, MEDLINE, Embase, LILACS, SCI-Expanded, BIOSIS for eligible trials comparing digoxin versus placebo, no intervention, or other medical interventions in patients with atrial fibrillation or atrial flutter in October 2016. Our primary outcomes were all-cause mortality, serious adverse events, and quality of life. Our secondary outcomes were heart failure, stroke, heart rate control, and conversion to sinus rhythm. We performed both random-effects and fixed-effect meta-analyses and chose the more conservative result as our primary result. We used Trial Sequential Analysis (TSA) to control for random errors. We used GRADE to assess the quality of the body of evidence.
RESULTS
28 trials (n = 2223 participants) were included. All were at high risk of bias and reported only short-term follow-up. When digoxin was compared with all control interventions in one analysis, we found no evidence of a difference on all-cause mortality (risk ratio (RR), 0.82; TSA-adjusted confidence interval (CI), 0.02 to 31.2; I2 = 0%); serious adverse events (RR, 1.65; TSA-adjusted CI, 0.24 to 11.5; I2 = 0%); quality of life; heart failure (RR, 1.05; TSA-adjusted CI, 0.00 to 1141.8; I2 = 51%); and stroke (RR, 2.27; TSA-adjusted CI, 0.00 to 7887.3; I2 = 17%). Our analyses on acute heart rate control (within 6 hours of treatment onset) showed firm evidence of digoxin being superior compared with placebo (mean difference (MD), -12.0 beats per minute (bpm); TSA-adjusted CI, -17.2 to -6.76; I2 = 0%) and inferior compared with beta blockers (MD, 20.7 bpm; TSA-adjusted CI, 14.2 to 27.2; I2 = 0%). Meta-analyses on acute heart rate control showed that digoxin was inferior compared with both calcium antagonists (MD, 21.0 bpm; TSA-adjusted CI, -30.3 to 72.3) and with amiodarone (MD, 14.7 bpm; TSA-adjusted CI, -0.58 to 30.0; I2 = 42%), but in both comparisons TSAs showed that we lacked information. Meta-analysis on acute conversion to sinus rhythm showed that digoxin compared with amiodarone reduced the probability of converting atrial fibrillation to sinus rhythm, but TSA showed that we lacked information (RR, 0.54; TSA-adjusted CI, 0.13 to 2.21; I2 = 0%).
CONCLUSIONS
The clinical effects of digoxin on all-cause mortality, serious adverse events, quality of life, heart failure, and stroke are unclear based on current evidence. Digoxin seems to be superior compared with placebo in reducing the heart rate, but inferior compared with beta blockers. The long-term effect of digoxin is unclear, as no trials reported long-term follow-up. More trials at low risk of bias and low risk of random errors assessing the clinical effects of digoxin are needed.
SYSTEMATIC REVIEW REGISTRATION
PROSPERO CRD42016052935.
Topics: Aged; Amiodarone; Atrial Fibrillation; Atrial Flutter; Bias; Calcium Channel Blockers; Comorbidity; Digoxin; Female; Heart Failure; Heart Rate; Humans; Male; Middle Aged; Mortality; Quality of Life; Randomized Controlled Trials as Topic; Research Design; Stroke; Treatment Outcome
PubMed: 29518134
DOI: 10.1371/journal.pone.0193924