Should Digoxin Continue To Be Used for the Management of Atrial Fibrillation?
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PROVIDER: S-EPMC5659251 | biostudies-literature | 2017 Sep-Oct
REPOSITORIES: biostudies-literature
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Should Digoxin Continue To Be Used for the Management of Atrial Fibrillation?
The Canadian journal of hospital pharmacy 20170901 5
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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:BackgroundRecently published analysis of contemporary atrial fibrillation (AF) cohorts showed an association between digoxin and increased mortality and hospitalizations; however, other studies have demonstrated conflicting results. Many AF cohort studies did not or were unable to examine racial differences. Our goal was to examine risk factors for hospitalizations and mortality with digoxin use in a diverse real-world AF patient population and evaluate racial differences.Methods and resultsWe performed a retrospective cohort analysis of claims data for Medicaid beneficiaries, aged 18 to 64 years, with incident diagnosis of AF in 2008 with follow-up until December 31, 2009. We created Kaplan-Meier curves and constructed multivariable Cox proportional hazard models for mortality and hospitalization. We identified 11 297 patients with an incident diagnosis of AF in 2008, of those, 1401 (12.4%) were on digoxin. Kaplan-Meier analysis demonstrated an increased risk of hospitalization with digoxin use overall and within race and heart failure groups. In adjusted models, digoxin was associated with an increased risk of hospitalization (adjusted hazard ratio, 1.54; 95% confidence interval, 1.39-1.70) and mortality (adjusted hazard ratio, 1.50; 95% confidence interval, 1.05-2.13). Overall, blacks had a higher risk of hospitalization but similar mortality when compared with whites regardless of digoxin use. We found no significant interaction between race and digoxin use for mortality (P=0.4437) and hospitalization (P=0.7122).ConclusionsOur study demonstrates an overall increased risk of hospitalizations and mortality with digoxin use but no racial/ethnic differences in outcomes were observed. Further studies including minority populations are needed to critically evaluate these associations.
| S-EPMC5522586 | biostudies-literature
Project description:Digoxin has long been used for rate control in atrial fibrillation (AF); its safety remains controversial.We performed a literature search using MEDLINE (source PubMed, January 1, 1966, to July 31, 2015) and EMBASE (January 1, 1980, to July 31, 2015) with no restrictions. Studies that reported relative risk (RR) estimates with 95% confidence intervals (CIs) for the associations of interest were included. Pooled effect estimates were obtained by using random-effects meta-analysis.Twenty-two studies involving 586,594 patients were identified. Patients taking digoxin, as compared with those who took no digoxin, experienced an increased risk of death from any cause (RR: 1.29[95% CI 1.16-1.43]), even after reported adjustment for propensity scores (RR: 1.28[95% CI 1.18-1.39]). The risk of death was increased with patients with or without heart failure (RR: 1.12[95% CI 1.02-1.23] and RR: 1.26[95% CI 1.15-1.29], respectively), and patients taking or not taking beta blockers (RR: 1.17 [95% CI 1.06-1.30] and RR: 1.28 [95% CI 1.08-1.51], respectively). Digoxin use was also associated with increased risk of cardiovascular death (RR: 1.32 [95% CI 1.07-1.64]), arrhythmic death (RR: 1.38 [95% CI 1.07-1.79]), and stroke (RR: 1.20 [95% CI 1.004-1.44]). Digoxin treatment is associated with an absolute risk increase of 19 (95% CI 13-26) additional deaths from any cause per 1000 person-years.Digoxin use is associated with a significant increased risk for death from any cause in patients with AF. This finding suggests a need for reconsideration of present treatment recommendations on use of digoxin in AF.
| S-EPMC4998364 | biostudies-literature
Project description:The mouse is a useful preclinical species for evaluating disease etiology due to the availability of a wide variety of genetically modified strains and the ability to perform disease-modifying manipulations. In order to establish an atrial filtration (AF) model in our laboratory, we profiled several commonly used murine AF models. We initially evaluated a pharmacological model of acute carbachol (CCh) treatment plus atrial burst pacing in C57BL/6 mice. In an effort to observe micro-reentrant circuits indicative of authentic AF, we employed optical mapping imaging in isolated mouse hearts. While CCh reduced atrial refractoriness and increased atrial tachyarrhythmia vulnerability, the left atrial (LA) excitation patterns were rather regular without reentrant circuits or wavelets. Therefore, the atrial tachyarrhythmia resembled high frequency atrial flutter, not typical AF per se. We next examined both a chronic angiotensin II (Ang II) infusion model and the surgical model of transverse aortic constriction (TAC), which have both been reported to induce atrial and ventricular structural changes that serve as a substrates for micro-reentrant AF. Although we observed some extent of atrial remodeling such as fibrosis or enlarged LA diameter, burst pacing-induced atrial tachyarrhythmia vulnerability did not differ from control mice in either model. This again suggested that an AF-like pathophysiology is difficult to demonstrate in the mouse. To continue searching for a valid murine AF model, we studied mice with a cardiac-specific deficiency (KO) in liver kinase B1 (Cardiac-LKB1), which has been reported to exhibit spontaneous AF. Indeed, the electrocardiograms (ECG) of conscious Cardiac-LKB1 KO mice exhibited no P waves and had irregular RR intervals, which are characteristics of AF. Histological evaluation of Cardiac-LKB1 KO mice revealed dilated and fibrotic atria, again consistent with AF. However, atrial electrograms and optical mapping revealed that electrical activity was limited to the sino-atrial node area with no electrical conduction into the atrial myocardium beyond. Thus, Cardiac-LKB1 KO mice have severe atrial myopathy or atrial standstill, but not AF. In summary, the atrial tachyarrhythmias we observed in the four murine models were distinct from typical human AF, which often exhibits micro- or macro-reentrant atrial circuits. Our results suggest that the four murine AF models we examined may not reflect human AF well, and raise a cautionary note for use of those murine models to study AF.
| S-EPMC8741011 | biostudies-literature
Project description:Digoxin is used for rate control in atrial fibrillation (AF), but evidence for its efficacy and safety after myocardial infarction (MI) is scarce and mixed. We studied post-MI digoxin use effects on AF patient outcomes in a nationwide registry follow-up study in Finland. Digoxin was used by 18.6% of AF patients after MI, with a decreasing usage trend during 2004-2014. Baseline differences in digoxin users (n = 881) and controls (n = 3898) were balanced with inverse probability of treatment weight adjustment. The median follow-up was 7.4 years. Patients using digoxin after MI had a higher cumulative all-cause mortality (77.4% vs. 72.3%; hazard ratio [HR]: 1.19; confidence interval [CI]: 1.07-1.32; p = 0.001) during a 10-year follow-up. Mortality differences were detected in a subgroup analysis of patients without baseline heart failure (HF) (HR: 1.23; p = 0.019) but not in patients with baseline HF (HR: 1.05; p = 0.413). Cumulative incidences of HF hospitalizations, stroke and new MI were similar between digoxin group and controls. In conclusion, digoxin use after MI is associated with increased mortality but not with HF hospitalizations, new MI or stroke in AF patients. Increased mortality was detected in patients without baseline HF. Results suggest caution with digoxin after MI in AF patients, especially in the absence of HF.
| S-EPMC9321089 | biostudies-literature
Project description: Not available
| S-EPMC1861122 | biostudies-literature
Project description:BackgroundAlthough digoxin has long been used to treat atrial fibrillation (AF) and heart failure (HF), its safety remains controversial.ObjectivesThis study sought to describe digoxin use over time in patients with AF who were stratified by the presence or absence of HF, to characterize the predictors of digoxin use and initiation, and to correlate digoxin use with outcomes.MethodsLongitudinal patterns of digoxin use and its association with a variety of outcomes were assessed in a prospective outpatient registry conducted at 174 U.S. sites with enrollment from June 2010 to August 2011.ResultsAmong 9,619 patients with AF and serial follow-up every 6 months for up to 3 years, 2,267 (23.6%) received digoxin at study enrollment, 681 (7.1%) were initiated on digoxin during follow-up, and 6,671 (69.4%) were never prescribed digoxin. After adjusting for other medications, heart rate was 72.9 beats/min among digoxin users and 71.5 beats/min among nonusers (p < 0.0001). Prevalent digoxin use at registry enrollment was not associated with subsequent onset of symptoms, hospitalization, or mortality (in patients with HF, adjusted hazard ratio [HR] for death: 1.04; without HF, HR: 1.22). Incident digoxin use during follow-up was not associated with subsequent death in patients with HF (propensity adjusted HR: 1.05), but was associated with subsequent death in those without HF (propensity adjusted HR: 1.99).ConclusionsAfter adjustment for detailed clinical factors, digoxin use in registry patients with AF had a neutral association with outcomes under most circumstances. Because of the multiple conflicting observational reports about digoxin's safety and possible concerns in specific clinical situations, a large pragmatic trial of digoxin therapy in AF is needed.
| S-EPMC4483195 | biostudies-literature
Project description: Not available
| S-EPMC5837211 | biostudies-literature
Project description:BackgroundDigoxin remains commonly used for rate control in atrial fibrillation, but limited data exist supporting this practice and some studies have shown an association with adverse outcomes. We examined the independent association between digoxin and risks of death and hospitalization in adults with incident atrial fibrillation and no heart failure.Methods and resultsWe performed a retrospective cohort study of 14,787 age, sex, and high-dimensional propensity score-matched adults with incident atrial fibrillation and no previous heart failure or digoxin use in the AnTicoagulation and Risk factors In Atrial fibrillation-Cardiovascular Research Network (ATRIA-CVRN) study within Kaiser Permanente Northern and Southern California. We examined the independent association between newly initiated digoxin and the risks of death and hospitalization using extended Cox regression. During a median 1.17 (interquartile range, 0.49-1.97) years of follow-up among matched patients with atrial fibrillation, incident digoxin use was associated with higher rates of death (8.3 versus 4.9 per 100 person-years; P<0.001) and hospitalization (60.1 versus 37.2 per 100 person-years; P<0.001). Incident digoxin use was independently associated with a 71% higher risk of death (hazard ratio, 1.71; 95% confidence interval, 1.52-1.93) and a 63% higher risk of hospitalization (hazard ratio, 1.63; 95% confidence interval, 1.56-1.71). Results were consistent in subgroups of age and sex and when using intent-to-treat or on-treatment analytic approaches.ConclusionsIn adults with atrial fibrillation, digoxin use was independently associated with higher risks of death and hospitalization. Given other available rate control options, digoxin should be used with caution in the management of atrial fibrillation.
| S-EPMC4334705 | biostudies-literature