Effect of Digoxin Therapy on Mortality in Patients With Atrial Fibrillation: An Updated Meta-Analysis
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SUBMITTER: Wang X
PROVIDER: S-EPMC8517124 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Digoxin is still commonly used in atrial fibrillation (AF) patients with and without heart failure (HF) for heart rate control. Studies concerning the detrimental effects of digoxin therapy in AF patients are inconsistent. This updated meta-analysis examined the association of digoxin therapy with all-cause mortality in AF patients, stratified by heart function status. We included observational studies with multivariate-adjusted data on digoxin and all-cause mortality in the analysis. The relative risks (RRs) of all-cause mortality were calculated and reported with 95% confidence intervals (95% CIs). Seventeen studies comprising 408,660 patients were included. Overall, in AF patients, digoxin treatment was associated with a significant increase in all-cause mortality after multivariate-adjustment (RR?=?1.22; 95% CI 1.15-1.30). When stratified by heart function status, digoxin treatment was associated with a 14% increase in all-cause mortality in AF patients with HF (RR?=?1.14, 95% CI 1.04-1.24), and a 36% increase in those without HF (RR?=?1.36, 95% CI 1.18-1.56). The increased risk of all-cause mortality was significantly higher in AF patients without HF compared with those with HF (P for interaction?=?0.04). This meta-analysis demonstrates that digoxin therapy was associated with a significant increase in all-cause mortality in AF patients, especially in those without HF. Given other available options, digoxin should be avoided as a first-line agent for heart rate control in AF patients.
| S-EPMC5291640 | biostudies-literature
Project description:Catheter ablation (CA) for atrial fibrillation (AF) is now an important therapeutic modality for patients with AF. However, data regarding changes in left atrial (LA) function after CA have indicated conflicting results depending on the AF types, follow-up period, and the analytical imaging tools. The objective of this review was to analyze the effect of CA on the LA size and function for patients with AF.We searched for studies regarding LA size and function pre- and post-ablation in PubMed, Embase, the Cochrane Library, and Web of Knowledge through May 2014. LA function was measured by LA ejective fraction (LAEF), LA active ejective fraction (LAAEF), or both. Total and subgroup analyses were implemented using Cochrane Review Manager Version 5.2. Weighted mean differences with 95% confidence intervals were used to express the results of continuous outcomes using fixed or random effect models. I2 was used to calculate heterogeneity. To assess publication bias, Egger's test and Begg's funnel plot were performed using Stata 12.0.Twenty-five studies (2040 enrolled patients) were selected for this meta-analysis. The LA diameter (LAD), maximum LA volume, and minimal LA volume were significantly decreased post-ablation, as compared with those at a pre-ablation visit. Compared with the pre-ablation outcomes, we found no significant differences in LAEF/LAAEF at a post-ablation follow-up. Decreases in LA volume and LAEF remained significant post-ablation for paroxysmal AF (PAF); however, the LAEF was insignificant changes in persistent AF (PeAF). Heterogeneity was significant in spite which individual study was excluded. A publication bias was not found. In a meta-regression analysis, we did not find any factor that contributed to the heterogeneity.With CA, LA volumes and LAD were decreased significantly in patients with AF; LAEF was not significant changes in patients with PeAF but decreased in those with PAF.
| S-EPMC4493108 | biostudies-literature
Project description:Recently 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.We 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).Our 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:Combination use of digoxin and other medications might lead to worse outcomes in patients with atrial fibrillation (AF). We sought to investigate whether digoxin-amiodarone combination would lead to worse outcome than digoxin alone in patients with AF. Adult patients with AF and received digoxin treatment from random samples of 1,000,000 individuals covered by the National Health Insurance in Taiwan were included. Baseline characteristics including risk factors and medications were matched by propensity score (PS) in those with and without addition of amiodarone treatment. A total of 5,040 AF patients taking digoxin therapy was included. PS matching identified 1,473 patients receiving digoxin-amiodarone combination and 2,660 patients receiving digoxin with a median follow-up of 1,331 days. Digoxin-amiodarone combination was associated with increased all-cause mortality (adjusted hazard ratio (HR): 1.640, 95% confidence interval (CI): 1.470-1.829, P?<?0.001). The risk of mortality increased regardless of duration of combination. Risk of sudden cardiac death was not increased in the combination group (HR: 1.304, 95% CI: 1.049-1.622, P?=?0.017). Death due to non-arrhythmic cardiac disease, cerebrovascular disease, and other vascular disease were higher in the combination group than the digoxin group. In conclusion, in patients with AF, digoxin-amiodarone combination therapy is associated with excess mortality than digoxin alone.
| S-EPMC7058044 | 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:BackgroundThe role of anticoagulation therapy for stroke prevention in older atrial fibrillation (AF) patients with chronic kidney disease (CKD) remains unclear. Therefore, we conducted a meta-analysis to explore the efficacy and safety of anticoagulation therapy in this population.MethodsThe Cochrane Library, PubMed, and Embase databases were systematically searched for studies reporting the effect of anticoagulation therapy in older patients with AF and CKD. The risk ratios (RRs) and 95% confidence intervals (CIs) were regarded as the risk estimates. A random-effects model selected was to evaluate the treatment outcomes. The presentations were based on the Preferred Reporting Items for reporting systematic reviews and meta-analyses statement.ResultsA total of 7 studies with 24,794 older patients with AF and CKD were included. The follow-up of the included studies ranged from 0.9 to 9.0 years. In older patients with no dialysis, compared with nonanticoagulants, anticoagulants reduced the risk of all-cause death (RR 0.66, 95% CI 0.54-0.79), but had comparable risks of ischemic stroke/transient ischemic attack (TIA, RR 0.91, 95% CI 0.46-1.79) and bleeding (RR 1.17, 95% CI 0.86-1.60). In older patients with dialysis, compared with nonanticoagulants, anticoagulants increased the risk of bleeding (RR 1.37, 95% CI 1.09-1.74), but had similar risks of ischemic stroke/TIA (RR 1.18, 95% CI 0.88-1.58) and death (RR 0.87, 95% CI 0.60-1.27).ConclusionCompared with nonanticoagulation, anticoagulation therapy is associated with a reduced risk of death in older AF patients with nondialysis, but an increased risk of bleeding in older patients with dialysis.
| S-EPMC6824694 | biostudies-literature
Project description:Despite endorsement of digoxin in clinical practice guidelines, there exist limited data on its safety in atrial fibrillation/flutter (AF).The goal of this study was to evaluate the association of digoxin with mortality in AF.Using complete data of the TREAT-AF (The Retrospective Evaluation and Assessment of Therapies in AF) study from the U.S. Department of Veterans Affairs (VA) healthcare system, we identified patients with newly diagnosed, nonvalvular AF seen within 90 days in an outpatient setting between VA fiscal years 2004 and 2008. We used multivariate and propensity-matched Cox proportional hazards to evaluate the association of digoxin use with death. Residual confounding was assessed by sensitivity analysis.Of 122,465 patients with 353,168 person-years of follow-up (age 72.1 ± 10.3 years, 98.4% male), 28,679 (23.4%) patients received digoxin. Cumulative mortality rates were higher for digoxin-treated patients than for untreated patients (95 vs. 67 per 1,000 person-years; p < 0.001). Digoxin use was independently associated with mortality after multivariate adjustment (hazard ratio [HR]: 1.26, 95% confidence interval [CI]: 1.23 to 1.29, p < 0.001) and propensity matching (HR: 1.21, 95% CI: 1.17 to 1.25, p < 0.001), even after adjustment for drug adherence. The risk of death was not modified by age, sex, heart failure, kidney function, or concomitant use of beta-blockers, amiodarone, or warfarin.Digoxin was associated with increased risk of death in patients with newly diagnosed AF, independent of drug adherence, kidney function, cardiovascular comorbidities, and concomitant therapies. These findings challenge current cardiovascular society recommendations on use of digoxin in AF.
| S-EPMC4405246 | biostudies-literature
Project description:BackgroundCurrent guidelines recommend the utilization of direct-acting oral anticoagulants (DOACs) in patients with non-valvular atrial fibrillation (AF). However, the optimal anticoagulation strategy for AF patients with bioprosthetic heart valves (BPHV) remains controversial. Therefore, we conducted this meta-analysis to explore the effect of DOACs versus vitamin K antagonists (VKAs) in this population.MethodsWe systematically searched the PubMed and Embase databases until November 2021 for studies reporting the effect of DOACs versus VKAs in AF patients with BPHV. Adjusted risk ratios (RRs) and 95% confidence intervals (CIs) were pooled using the random-effects model with an inverse variance method.ResultsWe selected four randomized clinical trials and seven observational studies (2236 DOAC- and 6403 VKAs-users). Regarding the effectiveness outcomes, there were no significant differences between DOACs and VKAs in stroke or systemic embolism (RR = 0.74, 95%CI: 0.50-1.08), ischemic stroke (RR = 1.08, 95%CI: 0.76-1.55), all-cause death (RR = 0.98, 95%CI: 0.86-1.12), and cardiovascular death (RR = 0.85, 95%CI: 0.40-1.80). In terms of the safety outcomes, DOACs was associated with lower risks of major bleeding (RR = 0.70, 95%CI: 0.59-0.82) and intracranial bleeding (RR = 0.42, 95%CI: 0.26-0.70), but the risks of any bleeding (RR = 0.85, 95%CI: 0.65-1.13) and gastrointestinal bleeding (RR = 0.92, 95%CI: 0.73-1.17) are not significantly different when compared with VKAs. The subgroup analysis with follow-up as a covariate revealed that the DOACs had lower risks of SSE (RR = 0.59, 95%CI: 0.37-0.94) and major bleeding (RR = 0.69, 95%CI: 0.58-0.81) in patients with a mean follow-up of more than 24 months, but no statistical differences were found in patients with the follow-up less than 24 months (SSE: RR = 1.10, 95%CI: 0.92-1.32; major bleeding: RR = 0.91, 95%CI: 0.42-2.01).ConclusionsIn AF with BPHV, patients on DOACs experienced a reduced risk of major bleeding and intracranial bleeding compared with VKAs, while the risks of stroke, cardiovascular death, and all-cause mortality were similar.
| S-EPMC9248967 | biostudies-literature
Project description:BackgroundDuring 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.MethodsWe 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.Results28 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%).ConclusionsThe 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 registrationPROSPERO CRD42016052935.
| S-EPMC5843263 | biostudies-literature
Project description:BackgroundRecent randomized controlled trials (RCTs) suggest that ablation is superior to antiarrhythmic drugs (AADs) as an initial therapy for paroxysmal atrial fibrillation (pAF) to prevent arrhythmia recurrences. We performed an updated meta-analysis of RCTs, to include recent data from cryoballoon-based ablation and to compare arrhythmia-free survival and adverse events between ablation and AADs.MethodsWe searched MEDLINE and EMBASE from inception to December 2020. We included RCT comparing patients with pAF undergoing ablation or receiving AADs as an initial therapy. We combined data using the random-effects model to calculate hazards ratio (HR) for arrhythmia-free survival and odds ratio (OR) for adverse events.ResultsFive studies from 2005 to 2020 involving 985 patients were included (495 patients and 490 patients underwent ablation and medication as initial therapy, respectively). Patients who underwent ablation had higher freedom from atrial tachyarrhythmias (ATs) during the 12-24 months follow-up period (pooled HR = 0.48, 95% CI: 0.40-0.59, P < .001). In a subgroup analysis of ablation method used, both cryoablation group (pooled HR = 0.49, 95% CI: 0.38-0.64, P < .001) and radiofrequency ablation group (pooled HR = 0.47, 95%CI: 0.35-0.64, P < .001) showed reduction in AT recurrence compared with AAD group. There were no differences in adverse events including cerebrovascular accident, pericardial effusion or tamponade, pulmonary vein stenosis, acute coronary syndrome, deep vein thrombosis and pulmonary embolism, and bradycardia requiring a pacemaker.ConclusionCatheter ablation (both cryoablation and radiofrequency ablation) is superior to AAD as an initial therapy for pAF in efficacy for reducing AT recurrences without a compromise in adverse events.
| S-EPMC8637078 | biostudies-literature