Assumption versus evidence: the case of digoxin in atrial fibrillation and heart failure.
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ABSTRACT:
SUBMITTER: Bavendiek U
PROVIDER: S-EPMC5837211 | biostudies-literature | 2017 Jul
REPOSITORIES: biostudies-literature
Publications
Assumption versus evidence: the case of digoxin in atrial fibrillation and heart failure.
Bavendiek Udo U Aguirre Davila Lukas L Koch Armin A Bauersachs Johann J
European heart journal 20170701 27
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Project description:BackgroundDigoxin is a cardiac glycoside, derived from the plant Digitalis purpurea. For many years digitalis has been widely used in the treatment of heart failure (HF), owing to its cardiotonic and neurohormonal effects and atrial fibrillation (AF), due to its parasympathomimetic effect on the AV node.ObjectiveThe aim of this paper is to evaluate the available evidence on the safety and efficacy of digoxin in patients with HF and AF, by reviewing the pertinent literature.MethodsWe conducted a PubMed/MEDLINE and SCOPUS search to evaluate the currently available evidence on the administration of digoxin and its association with all-cause mortality risk in patients with AF and HF.ResultsSeveral observational analyses of clinical trials and meta-analyses have shown conflicting results on the safety and efficacy of digoxin administration in patients with AF and HF. According to these results, digoxin should be avoided in patients without HF, as it is associated with worse outcomes. On the other hand, in patients with AF and HF digoxin should be used with caution.ConclusionThe impact of digoxin on all-cause mortality and adverse effects in these patients remains unclear based on the current evidence. More trials at low risk of bias evaluating the effects of digoxin are needed.
| S-EPMC8976896 | biostudies-literature
Project description:In patients with atrial fibrillation (AF) and heart failure (HF) with or without systolic dysfunction, either rhythm control or rate control is an acceptable primary therapeutic option. If a rate control strategy is chosen, treatment with a beta-blocker is almost always required to achieve rate control. Adequate ventricular rate control is usually a resting rate of less than 100 beats per minute, but lower resting rates may be appropriate. Non-dihydropyridine calcium channel blockers are often contraindicated when AF is associated with HF with systolic dysfunction. There have been recent debates on a possible reduced efficacy of beta-blockers as well as safety issues with digoxin when treating HF patients with AF. The benefit of beta-blockers on survival may be lower in patients with HF with reduced ejection fraction when AF is present. Digoxin does not improve survival but may help to obtain satisfactory rate control in combination with a beta-blocker. Digoxin may be useful in the presence of hypotension or an absolute contraindication to beta-blocker treatment.
| S-EPMC5490978 | biostudies-other
Project description:Digoxin is widely used to treat various heart conditions. In order to clarify the association between digoxin and anemia adverse reaction, we inspected case reports submitted to the FDA Adverse Event Reporting System (FAERS) between January 2004 and December 2015. These reports involved 75618 atrial fibrillation patients and 15699 heart failure patients. Compared to other therapies, digoxin treatment was significantly more likely to be concurrent with anemia adverse reaction among both atrial fibrillation patients (pooled OR = 1.38, 95% CI 1.14-1.68, P-value = 0.001) and heart failure patients (pooled OR =1.50, 95% CI 1.33-1.59-, P =4.27×10-5). We further explored previously published evidences and found 821 human genes directly or indirectly interacting with digoxin. Functional analysis indicated that these genes were significantly enriched in the biological processes of iron transport, which are closely related to iron deficiency anemia. Taken together, our retrospective analysis demonstrated the significant association between digoxin treatment and anemia adverse reaction, which should be seriously considered in clinical practice. Functional enrichment analysis on digoxin-related genes warranted subsequent research on the underlying toxicological mechanisms.
| S-EPMC5593620 | biostudies-literature
Project description:BackgroundThere are few prospective studies assessing the benefits of rhythm control of atrial fibrillation (AF) in patients with heart failure and preserved ejection fraction (HFpEF), which accounts for 50% of all heart failure patients.ObjectiveConduct a meta-analysis to assess the effects of rhythm control (ablation and/or antiarrhythmic medications) vs rate control on all-cause mortality in AF patients with HFpEF.MethodsDatabases were searched for studies reporting the effect of rhythm control vs rate control on mortality in patients with HFpEF (Ovid MEDLINE, EMBASE, Scopus, Web of Science, Google Scholar, and EBSCO CINAHL). The search was not restricted to time or publication status. The primary endpoint was all-cause mortality. The minimum duration of follow-up required for inclusion was 1 year.ResultsThe literature search identified 1210 candidate studies; 5 studies and 16,825 patients were included. The study population had 57% men with a mean age of 71± 2.5 years. Rhythm control for AF was associated with lower all-cause mortality (odds ratio 0.735, 95% confidence interval 0.665-0.813; P < .001) as compared to rate control.ConclusionRhythm control for AF in patients with HFpEF was associated with decreased all-cause mortality.
| S-EPMC9626734 | biostudies-literature
Project description:BackgroundIn patients with heart failure and atrial fibrillation (AF), several clinical trials have reported improved outcomes, including freedom from AF recurrence, quality of life, and survival, with catheter ablation. This article describes the treatment-related outcomes of the AF patients with heart failure enrolled in the CABANA trial (Catheter Ablation Versus Antiarrhythmic Drug Therapy for Atrial Fibrillation).MethodsThe CABANA trial randomized 2204 patients with AF who were ≥65 years old or <65 years old with ≥1 risk factor for stroke at 126 sites to ablation with pulmonary vein isolation or drug therapy including rate or rhythm control drugs. Of these, 778 (35%) had New York Heart Association class >II at baseline and form the subject of this article. The CABANA trial's primary end point was a composite of death, disabling stroke, serious bleeding, or cardiac arrest.ResultsOf the 778 patients with heart failure enrolled in CABANA, 378 were assigned to ablation and 400 to drug therapy. Ejection fraction at baseline was available for 571 patients (73.0%), and 9.3% of these had an ejection fraction <40%, whereas 11.7% had ejection fractions between 40% and 50%. In the intention-to-treat analysis, the ablation arm had a 36% relative reduction in the primary composite end point (hazard ratio, 0.64 [95% CI, 0.41-0.99]) and a 43% relative reduction in all-cause mortality (hazard ratio, 0.57 [95% CI, 0.33-0.96]) compared with drug therapy alone over a median follow-up of 48.5 months. AF recurrence was decreased with ablation (hazard ratio, 0.56 [95% CI, 0.42-0.74]). The adjusted mean difference for the AFEQT (Atrial Fibrillation Effect on Quality of Life) summary score averaged over the entire 60-month follow-up was 5.0 points, favoring the ablation arm (95% CI, 2.5-7.4 points), and the MAFSI (Mayo Atrial Fibrillation-Specific Symptom Inventory) frequency score difference was -2.0 points, favoring ablation (95% CI, -2.9 to -1.2).ConclusionsIn patients with AF enrolled in the CABANA trial who had clinically diagnosed stable heart failure at trial entry, catheter ablation produced clinically important improvements in survival, freedom from AF recurrence, and quality of life relative to drug therapy. These results, obtained in a cohort most of whom had preserved left ventricular function, require independent trial verification. Registration: URL: https://www.clinicaltrials.gov/ct2/show/NCT00911508; Unique identifier: NCT0091150.
| S-EPMC8030730 | biostudies-literature
Project description:BackgroundObservational studies have suggested a close association between atrial fibrillation (AF) and heart failure (HF), yet the causal effect remains uncertain. In this study, we employed a bidirectional Mendelian randomization analysis to investigate the causal effect of one disease on the other.MethodsGenetic instrumental variables were obtained from large-scale summary-level genome-wide association studies of AF (n = 1,030,836) and HF(n = 1,665,481), respectively. Two-sample Mendelian randomization was conducted to establish causal inferences. Inverse-variance weighted (IVW) was the primary estimate, while additional analyses including MR Pleiotropy RESidual Sum and Outlier (MR-PRESSO), MR-Egger, and Weighted median were performed to validate robustness and identify pleiotropy.ResultsAfter accounting for confounding variables, MR analysis suggested a potential causal relationship between AF and HF. An augmented genetic predisposition to atrial fibrillation was associated with an elevated risk of heart failure (odds ratio (OR) = 1.18, 95% confidence interval (CI):1.14-1.22). Likewise, genetically determined heart failure also increased the risk of heart failure (OR = 1.44, 95%CI:1.23-1.68). The robustness of the findings was corroborated through MR sensitivity analyses, and the causal estimates remained consistent when the instrument P-value threshold was tightened.ConclusionsOur bidirectional Mendelian randomization study supports a reciprocal causal relationship between AF and HF. The shared genetic profile of these conditions may provide crucial insights into potential therapeutic targets for the prevention and progression of both disorders. These findings underscore the necessity for further investigation into the underlying molecular mechanisms linking AF and HF, as well as the potential for personalized treatment strategies grounded in genetic profiling.
| S-EPMC10424396 | biostudies-literature
Project description:Digoxin is widely used in patients with atrial fibrillation despite the lack of randomized controlled trials. Observational studies report conflicting results regarding its association with mortality, perhaps because of residual confounding by the presence of heart failure (HF). In the ENGAGE AF-TIMI 48 (Effective Anticoagulation With Factor Xa Next Generation in Atrial Fibrillation-Thrombolysis in Myocardial Infarction 48) trial, clinical outcomes of patients with atrial fibrillation with and without HF were examined by baseline digoxin use during a median follow-up of 2.8 years. HF was defined at baseline as prior or current clinical stage C or D HF. Of 21 105 patients enrolled, 6327 (30%) were treated with digoxin at baseline. Among patients without HF (n=8981), digoxin use (20%) was independently associated with sudden cardiac death (adjusted hazard ratio, 1.51; 95% CI, 1.10-2.08), with no significant interaction by age, sex, left ventricular ejection fraction, renal function, or concomitant medications (P>0.05 for each). Consistent results were observed using propensity matching (adjusted hazard ratio for sudden cardiac death, 1.90; 95% CI, 1.36-2.65). Among patients with HF (n=12 124), digoxin use (37%) was associated with an increase in all-cause death, cardiovascular death, sudden cardiac death, and death caused by HF/cardiogenic shock (P<0.01 for each), but not with noncardiovascular death, stroke/systemic embolism, or myocardial infarction. In this observational analysis of patients with atrial fibrillation without investigator-reported HF, digoxin use was significantly associated with sudden cardiac death. While residual confounding cannot be excluded, the association between digoxin use and worse clinical outcomes highlights the need to examine digoxin use, particularly when prescribed to control heart rate in patients with atrial fibrillation in a randomized trial. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00781391.
| S-EPMC5586309 | biostudies-literature
Project description:BackgroundHeart failure (HF) and atrial fibrillation (AF) are often concomitant and act in a vicious cycle. Atrial fibrillation is associated with greater functional limitations and increased morbidity and mortality in patients with HF. Moreover, AF associated with HF increases patients' physical inactivity, worsening their clinical condition, and prognosis. Exercise training is safe and has clear benefits in HF. However, these benefits have not been demonstrated when AF is associated with HF.Case summaryWe present the case of a 57-year-old man with permanent AF and HF with reduced ejection fraction, who underwent 12 weeks of exercise training that included cardiopulmonary exercise testing, neuromuscular sympathetic activity (NMSA), and muscle blood flow (MBF) before and after training.DiscussionExercise training was shown to have a potential benefit in reducing the activity of the sympathetic nerve and increasing muscle blood flow, as well as increasing VO2peak and decreasing the VE/VCO2 slope in a patient with AF associated with HF with reduced ejection fraction. These results may indicate favourable clinical implications in this group of patients.
| S-EPMC7649495 | biostudies-literature
Project description:Many trials have shown improvements in left ventricular function, exercise capacity, and quality of life after catheter ablation (CA) of atrial fibrillation (AF) in patients with heart failure (HF). We sought to evaluate the impact of CA on hard outcomes in a retrospective cohort study. AF patients with symptomatic HF from 3 hospitals were included. Our primary endpoint was major adverse cardiac events (MACEs), a composite of all-cause mortality, stroke, and unplanned hospitalization. In total, 90 patients underwent CA and 304 ones received rate control (RaC) were included. After a mean follow-up of 13.5?±?5.3 months, 82.2% of patients in CA group got freedom from AF; all patients in RaC group remained in AF. CA group had a significant decreased risk of MACEs compared with RaC group (13.3% vs 29.3%, hazard ratio [HR] 0.51, 95% confidence interval [CI]: 0.32-0.82, P?=?.005). After propensity score matched for confounding factors, difference in MACEs remained significant between groups (13.3% vs 25.6%, HR 0.50, 95% CI: 0.26-0.98, P?=?.044). Multivariate regression analysis also indicated that CA was significantly associated with a lower risk of MACEs in overall cohort (HR 0.486, 95% CI: 0.253-0.933, P?=?.030) and in propensity-matched cohort (HR 0.482, 95% CI: 0.235-0.985, P?=?.045). Besides, age and NYHA class were associated with an increased risk of MACEs. In conclusion, the present study demonstrated that CA for AF in HF patients could reduce the risk of MACEs in a mid-term follow-up. Thus, CA may be a reasonable option for this population.
| S-EPMC5728981 | biostudies-literature
Project description:IntroductionCatheter ablation has shown to reduce mortality in patient with atrial fibrillation (AF) and heart failure (HF) with reduced ejection fraction. Its effect on mortality in patients without HF has not been well elucidated.MethodsThirteen randomized controlled trials encompassing 3856 patients were selected using PubMed, Embase and the CENTRAL till April 2019. Estimates were reported as random effects risk ratio (RR) with 95% confidence intervals (CI).ResultsCompared with medical therapy, catheter ablation did not reduce the risk of all-cause mortality (RR, 0.86, 95% CI, 0.62-1.19, P=0.36; I2=0), stroke (RR, 0.55, 95% CI, 0.18-1.66, P=0.29; I2=0), need for cardioversion (RR, 0.84, 95% CI, 0.66-1.08, P=0.17; I2=0) or pacemaker (RR, 0.59, 95% CI, 0.34-1.01, P=0.06; I2=0). However, ablation reduced the RR of cardiac hospitalization (0.37, 95% CI, 0.18-0.77, P=0.01; I2=86), and recurrent atrial arrhythmia (0.46, 95% CI, 0.35-0.60, P<0.001; I2=87). There were non-significant differences among treatment groups with respect to major bleeding (RR, 1.89, 95% CI, 0.59-6.08, P=0.29; I2=15), and pulmonary vein stenosis (RR, 3.00, 95% CI, 0.83-10.87, P=0.09; I2=0), but had significantly higher rates of pericardial tamponade (RR, 4.46, 95 % CI, 1.70-11.72, P<0.001; I2=0).ConclusionsCatheter ablation did not improve survival compared with medical therapy in patients with AF without HF. Catheter ablation reduced cardiac hospitalization and recurrent atrial arrhythmia at the expense of pericardial tamponade.
| S-EPMC7533121 | biostudies-literature