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Circulation. Heart Failure Jan 2017Treatments that reduce mortality and morbidity in patients with heart failure with reduced ejection fraction, including angiotensin-converting enzyme inhibitors (ACEI),... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Treatments that reduce mortality and morbidity in patients with heart failure with reduced ejection fraction, including angiotensin-converting enzyme inhibitors (ACEI), angiotensin receptor blockers (ARB), β-blockers (BB), mineralocorticoid receptor antagonists (MRA), and angiotensin receptor-neprilysin inhibitors (ARNI), have not been studied in a head-to-head fashion. This network meta-analysis aimed to compare the efficacy of these drugs and their combinations regarding all-cause mortality in patients with heart failure with reduced ejection fraction.
METHODS AND RESULTS
A systematic literature review identified 57 randomized controlled trials published between 1987 and 2015, which were compared in terms of study and patient characteristics, baseline risk, outcome definitions, and the observed treatment effects. Despite differences identified in terms of study duration, New York Heart Association class, ejection fraction, and use of background digoxin, a network meta-analysis was considered feasible and all trials were analyzed simultaneously. The random-effects network meta-analysis suggested that the combination of ACEI+BB+MRA was associated with a 56% reduction in mortality versus placebo (hazard ratio 0.44, 95% credible interval 0.26-0.66); ARNI+BB+MRA was associated with the greatest reduction in all-cause mortality versus placebo (hazard ratio 0.37, 95% credible interval 0.19-0.65). A sensitivity analysis that did not account for background therapy suggested that ARNI monotherapy is more efficacious than ACEI or ARB monotherapy.
CONCLUSIONS
The network meta-analysis showed that treatment with ACEI, ARB, BB, MRA, and ARNI and their combinations were better than the treatment with placebo in reducing all-cause mortality, with the exception of ARB monotherapy and ARB plus ACEI. The combination of ARNI+BB+MRA resulted in the greatest mortality reduction.
Topics: Chronic Disease; Heart Failure; Humans; Network Meta-Analysis; Randomized Controlled Trials as Topic; Stroke Volume; Treatment Outcome; Ventricular Dysfunction, Left
PubMed: 28087688
DOI: 10.1161/CIRCHEARTFAILURE.116.003529 -
International Journal of Clinical... Feb 2017Background QTc-interval prolongation has been associated with serious adverse events, such as Torsade de Pointes and sudden cardiac death. In the prevention of... (Meta-Analysis)
Meta-Analysis Review
Background QTc-interval prolongation has been associated with serious adverse events, such as Torsade de Pointes and sudden cardiac death. In the prevention of QTc-prolongation, special attention should go to high-risk patients. Aim of the review The aim of this review is to summarize and assess the evidence for different risk factors for QTc-prolongation (demographic factors, comorbidities, electrolytes, QTc-prolonging medication). Methods Potential studies were retrieved based on a systematic search of articles published until June 2015 in the databases Medline and Embase. Both terms about QTc-prolongation/Torsade de Pointes and risk factors were added in the search strategy. The following inclusion criteria were applied: randomized controlled trials and observational studies; inclusion of ≥500 patients from a general population (not limited to specific disease states); assessment of association between QTc-interval and risk factors. For the articles that met the inclusion criteria, the following data were extracted: study design, setting and study population, number of patients and cases of QTc-prolongation, method of electrocardiogram-monitoring, QTc-correction formula, definition of QTc-prolongation, statistical methods and results. Quality assessment was performed using the GRADE approach (for randomized controlled trials) and the STROBE-recommendations (for observational studies). Based on the number of significant results and the level of significance, a quotation of the evidence was allocated. Results Ten observational studies could be included, with a total of 89,532 patients [prospective cohort design: N = 6; multiple regression analyses: N = 5; median STROBE score = 17/22 (range 15-18)]. Very strong evidence was found for hypokalemia, use of diuretics, antiarrhythmic drugs and QTc-prolonging drugs of list 1 of CredibleMeds. Little or no evidence was found for hyperlipidemia, the use of digoxin or statins, neurological disorders, diabetes, renal failure, depression, alcohol abuse, heart rate, pulmonary disorders, hormone replacement therapy, hypomagnesemia, history of a prolonged QTc-interval/Torsade de Pointes, familial history of cardiovascular disease, and the use of only QTc-prolonging drugs of list 2 or 3 of CredibleMeds. Conclusion This systematic review gives a clear overview of the available evidence for a broad range of risk factors for QTc-prolongation.
Topics: Age Factors; Anti-Arrhythmia Agents; Brugada Syndrome; Cardiac Conduction System Disease; Diuretics; Electrocardiography; Humans; Long QT Syndrome; Prospective Studies; Randomized Controlled Trials as Topic; Risk Factors; Smoking
PubMed: 28012118
DOI: 10.1007/s11096-016-0414-2 -
The Journal of Cardiovascular Nursing 2016Many heart failure patients show fall-related signs/symptoms including postural hypotension, cerebellar injury, and cognitive impairments. Falls contribute to injuries,... (Review)
Review
BACKGROUND
Many heart failure patients show fall-related signs/symptoms including postural hypotension, cerebellar injury, and cognitive impairments. Falls contribute to injuries, increased healthcare use, and death, but falls have been understudied in this population.
OBJECTIVE
The purpose of this review is to identify fall rates, fall injuries, and risk factors for falls in heart failure patients.
METHODS
A systematic literature review was conducted using MEDLINE, CINAHL, PubMed, PsycINFO, and Cochrane Library to identify publications from August 1973 to June 2013. Keywords were accidental falls, heart failure, fall rates, fall injuries, and fall risk. Inclusion criteria were publications that were primary data based, included heart failure sample, had falls/fall risk as study variables, and were written in English language. Exclusion criteria were quality improvement/evaluation, case reports/studies, news, opinions, narrative reviews, meeting reports, reflections, and letters to editors. Data were abstracted using a standardized data collection form.
RESULTS
Four publications met the inclusion criteria. In the first study, fall rate was 43%, which is higher than the fall rates among community-dwelling older adults. Fall-related injuries were not examined in any of studies. Benzodiazepines and digoxin were identified as medications that increased risk of falls in 1 case-control study. Loop diuretics were not significantly associated with falls in 1 cohort study. In the fourth study, patients who had poor gait and balance were at greater risk of falling.
CONCLUSIONS
Future studies are needed to determine factors associated with falls, characterize injuries resulting from falls, and most importantly design testable interventions to prevent falls in heart failure patients.
Topics: Accidental Falls; Case-Control Studies; Cohort Studies; Heart Failure; Humans; Risk Factors
PubMed: 26422636
DOI: 10.1097/JCN.0000000000000292 -
International Journal of Cardiology Nov 2016Right heart failure is associated with increased mortality and morbidity. The optimal treatment for patients with RV failure is not established. The aim of this study is... (Review)
Review
OBJECTIVE
Right heart failure is associated with increased mortality and morbidity. The optimal treatment for patients with RV failure is not established. The aim of this study is to conduct a systematic review of the literature to assess the relative benefits and harms of digoxin therapy in patients with RV failure.
METHODS
We performed a literature search in MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials (CENTRAL) on Nov. 4, 2014. We did not use publication type, period or language restrictions to the search strategy. Exclusions included: trials that excluded patients with RV failure, included patients requiring mechanical or intravenous inotropic support, review papers and case reports. The primary outcome was long-term efficacy outcomes of digoxin in right heart failure. Two reviewers screened titles and abstracts of identified citations independently and in duplication using calibration exercises and standardized screening forms.
RESULTS
The search strategy identified 4097 citations, and 4 studies were included in this analysis (n=76 patients). Of the four studies, two assessed improvements in RVEF, two studies compared exercise capacity indexes, and one assessed symptoms with digoxin compared with placebo. No study assessed mortality outcomes. Overall, there was no statistically significant improvement in RVEF, exercise capacity, NYHA class, heart failure score, or body weight.
CONCLUSIONS
There are few studies evaluating Digitalis use for RV failure, which are limited to patients with cor pulmonale. In these patients, Digitalis use provides no improvement in RVEF, exercise capacity, or NYHA class. Randomized clinical trials are needed to address this question.
Topics: Cardiotonic Agents; Digoxin; Humans; Pulmonary Heart Disease; Treatment Outcome
PubMed: 27543702
DOI: 10.1016/j.ijcard.2016.08.018 -
Cardiology Journal 2016There is growing controversy regarding the association between digoxin and mortality in atrial fibrillation (AF). The aim of this analysis was to systematically review... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
There is growing controversy regarding the association between digoxin and mortality in atrial fibrillation (AF). The aim of this analysis was to systematically review digoxin use and risk of mortality in patients with AF.
METHODS
MEDLINE, EMBASE, GoogleScholar, CINAHL, meeting abstracts, presentations, and Cochrane central databases were searched from inception through December 2014, without language restrictions. For a study to be selected, it had to report the risk of mortality associated with digoxin use in AF patients as an outcome measure. Data were extracted by 2 independent authors. Evidence tables were created.
RESULTS
A total of 16 studies (6 post hoc analyses of randomized controlled trials) with 111,978 digoxin users and 389,643 non-digoxin users were included. In a random effects model, patients treated with digoxin had a 27% increased risk of all-cause mortality (pooled HR 1.27; 95% CI 1.19-1.36) and 21% increased risk of cardiovascular mortality (pooled HR 1.21; 95% CI 1.12-1.30) compared with those who did not use digoxin. In a random effects model, the association of digoxin with all-cause mortality was stronger for AF patients without heart failure (pooled HR 1.47; 95% CI 1.25-1.73) than AF patients with heart failure (pooled HR 1.21; 95% CI 1.07-1.36, interaction p = 0.06).
CONCLUSIONS
Digoxin use in AF is associated with increased risk of all-cause and cardiovascular mortalities. The effect size was larger for AF patients without heart failure than AF patients with heart failure. The study suggests further directed analyses to study the effect that is suggested by this meta-analysis, especially in AF without heart failure.
Topics: Anti-Arrhythmia Agents; Atrial Fibrillation; Digoxin; Global Health; Humans; Survival Rate
PubMed: 27064796
DOI: 10.5603/CJ.a2016.0016 -
Clinical Toxicology (Philadelphia, Pa.) 2016The Extracorporeal Treatments in Poisoning (EXTRIP) workgroup was formed to provide recommendations on the use of extracorporeal treatments (ECTR) in poisoning. Here, we... (Review)
Review
BACKGROUND
The Extracorporeal Treatments in Poisoning (EXTRIP) workgroup was formed to provide recommendations on the use of extracorporeal treatments (ECTR) in poisoning. Here, we present our results for digoxin.
METHODS
After a systematic literature search, clinical and toxicokinetic data were extracted and summarized following a predetermined format. The entire workgroup voted through a two-round modified Delphi method to reach a consensus on voting statements. A RAND/UCLA Appropriateness Method was used to quantify disagreement, and anonymous votes were compiled and discussed in person. A second vote was conducted to determine the final workgroup recommendations.
RESULTS
Out of 435 articles screened, 77 met inclusion criteria. Only in-vitro, animal studies, case reports and case series were identified yielding a very low quality of evidence for all recommendations. Based on data from 84 patients, including six fatalities, it was concluded that digoxin is slightly dialyzable (level of evidence = B), and that ECTR is unlikely to improve the outcome of digoxin-toxic patients whether or not digoxin immune Fab (Fab) is administered. Despite the lack of robust clinical evidence, the workgroup recommended against the use of ECTR in cases of severe digoxin poisoning when Fab was available (1D) and also suggested against the use of ECTR when Fab was unavailable (2D).
CONCLUSION
ECTR, in any form, is not indicated for either suspected or proven digoxin toxicity, regardless of the clinical context, and is not indicated for removal of digoxin-Fab complex.
Topics: Animals; Cardiotonic Agents; Consensus; Delphi Technique; Digoxin; Disease Models, Animal; Drug Overdose; Drug-Related Side Effects and Adverse Reactions; Humans; Randomized Controlled Trials as Topic; Renal Dialysis
PubMed: 26795743
DOI: 10.3109/15563650.2015.1118488 -
Journal of Cardiovascular Pharmacology Apr 2016Atrial fibrillation (AF), which increases morbidity and mortality, is a common occurrence after thoracic surgery and pulmonary resection. Despite several investigations... (Meta-Analysis)
Meta-Analysis Review
Atrial fibrillation (AF), which increases morbidity and mortality, is a common occurrence after thoracic surgery and pulmonary resection. Despite several investigations on various prophylactic measures for AF prevention, the studies were not uniform and do not use similar controls making it difficult to arrive at a meaningful conclusion. In the present systematic analysis review, we evaluated the efficacy of different prophylactic approaches to prevent AF after lung surgery in randomized trials reported during 1991-2014. A total of 12 trials were identified that met the criteria set for this meta-analysis. Among different trials, amiodarone was found to be most effective in preventing postoperative AF (risk ratio, 0.22; P < 0.0001; 95% confidence interval: 0.09-0.54). There were no significant prophylactic effects by MgSO4 (risk ratio, 1.24; P < 0.007; 95% confidence interval, 0.27-5.68), digoxin, or Ca blockers. Single use of amiodarone was able to lower the incidence of AF from 39.2% to 8.3% and seemed to be safe with no major complications. Although several prophylactic measures have been tried to curtail the incidence of AF in patients after lung surgery, prophylaxis with amiodarone seems to be most effective of treatments studied.
Topics: Amiodarone; Atrial Fibrillation; Humans; Incidence; Lung; Pneumonectomy; Postoperative Complications; Randomized Controlled Trials as Topic; Thoracic Surgical Procedures
PubMed: 26779893
DOI: 10.1097/FJC.0000000000000351 -
World Journal of Cardiology Nov 2015To review digoxin use in systolic congestive heart failure, atrial fibrillation, and after myocardial infarction.
AIM
To review digoxin use in systolic congestive heart failure, atrial fibrillation, and after myocardial infarction.
METHODS
A comprehensive PubMed search was performed using the key words "digoxin and congestive heart failure", "digoxin and atrial fibrillation", "digoxin, atrial fibrillation and systolic congestive heart failure", and "digoxin and myocardial infarction". Only articles written in English were included in this study. We retained studies originating from randomized controlled trials, registries and included at least 500 patients. The studies included patients with atrial fibrillation or heart failure or myocardial infarction and had a significant proportion of patients (at least 5%) on digoxin. A table reviewing the different hazard ratios was developed based on the articles selected. Our primary endpoint was the overall mortality in the patients on digoxin vs those without digoxin, among patients with atrial fibrillation and also among patients with atrial fibrillation and systolic heart failure. We reviewed the most recent international guidelines to discuss current recommendations.
RESULTS
A total of 18 studies were found that evaluated digoxin and overall mortality in different clinical settings including systolic congestive heart failure and normal sinus rhythm (n = 5), atrial fibrillation with and without systolic congestive heart failure (n = 9), and myocardial infarction (n = 4). Overall, patients with systolic congestive heart failure with normal sinus rhythm, digoxin appears to have a neutral effect on mortality especially if close digoxin level monitoring is employed. However, most of the observational studies evaluating digoxin use in atrial fibrillation without systolic congestive heart failure showed an increase in overall mortality when taking digoxin. In the studies evaluated in this systematic review, the data among patients with atrial fibrillation and systolic congestive heart failure, as well as post myocardial infarction were more controversial. The extent to which discrepancies among studies are based on statistical methods is currently unclear, as these studies' findings are generated by retrospective analyses that employed different techniques to address confounding.
CONCLUSION
Based on the potential risks and benefits, as well as the presence of alternative drugs, there is a limited role for digoxin in the management of patients with normal sinus rhythm and congestive heart failure. Based on the retrospective studies reviewed there is a growing volume of data showing increased mortality in those with only atrial fibrillation. The proper role of digoxin is, however, less certain in other subgroups of patients, such as those with both atrial fibrillation and systolic congestive heart failure or after a myocardial infarction. Further studies may provide helpful information for such subgroups of patients.
PubMed: 26635929
DOI: 10.4330/wjc.v7.i11.808 -
BMJ (Clinical Research Ed.) Sep 2015
PubMed: 26374771
DOI: 10.1136/bmj.h4937 -
BMJ (Clinical Research Ed.) Aug 2015To clarify the impact of digoxin on death and clinical outcomes across all observational and randomised controlled trials, accounting for study designs and methods. (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
To clarify the impact of digoxin on death and clinical outcomes across all observational and randomised controlled trials, accounting for study designs and methods.
DATA SOURCES AND STUDY SELECTION
Comprehensive literature search of Medline, Embase, the Cochrane Library, reference lists, and ongoing studies according to a prospectively registered design (
PROSPERO
CRD42014010783), including all studies published from 1960 to July 2014 that examined treatment with digoxin compared with control (placebo or no treatment).
DATA EXTRACTION AND SYNTHESIS
Unadjusted and adjusted data pooled according to study design, analysis method, and risk of bias.
MAIN OUTCOME MEASURES
Primary outcome (all cause mortality) and secondary outcomes (including admission to hospital) were meta-analysed with random effects modelling.
RESULTS
52 studies were systematically reviewed, comprising 621,845 patients. Digoxin users were 2.4 years older than control (weighted difference 95% confidence interval 1.3 to 3.6), with lower ejection fraction (33% v 42%), more diabetes, and greater use of diuretics and anti-arrhythmic drugs. Meta-analysis included 75 study analyses, with a combined total of 4,006,210 patient years of follow-up. Compared with control, the pooled risk ratio for death with digoxin was 1.76 in unadjusted analyses (1.57 to 1.97), 1.61 in adjusted analyses (1.31 to 1.97), 1.18 in propensity matched studies (1.09 to 1.26), and 0.99 in randomised controlled trials (0.93 to 1.05). Meta-regression confirmed that baseline differences between treatment groups had a significant impact on mortality associated with digoxin, including markers of heart failure severity such as use of diuretics (P=0.004). Studies with better methods and lower risk of bias were more likely to report a neutral association of digoxin with mortality (P<0.001). Across all study types, digoxin led to a small but significant reduction in all cause hospital admission (risk ratio 0.92, 0.89 to 0.95; P<0.001; n=29,525).
CONCLUSIONS
Digoxin is associated with a neutral effect on mortality in randomised trials and a lower rate of admissions to hospital across all study types. Regardless of statistical analysis, prescription biases limit the value of observational data.
Topics: Atrial Fibrillation; Cardiotonic Agents; Digoxin; Heart Failure; Hospitalization; Humans; Outcome Assessment, Health Care; Treatment Outcome
PubMed: 26321114
DOI: 10.1136/bmj.h4451