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European Journal of Clinical... Apr 2023To perform a systematic umbrella review with meta-analysis to evaluate the certainty of evidence on mortality risk associated with digoxin use in patients with atrial... (Meta-Analysis)
Meta-Analysis Review
Effect of digoxin on all-cause and cardiovascular mortality in patients with atrial fibrillation with and without heart failure: an umbrella review of systematic reviews and 12 meta-analyses.
PURPOSE
To perform a systematic umbrella review with meta-analysis to evaluate the certainty of evidence on mortality risk associated with digoxin use in patients with atrial fibrillation (AF) with or without heart failure (HF).
METHODS
We systematically searched MEDLINE, Embase, and Web of Science databases from inception to 19 October 2021. We included systematic reviews and meta-analyses of observational studies investigating digoxin effects on mortality of adult patients with AF and/or HF. The primary outcome was all-cause mortality; secondary outcome was cardiovascular mortality. Certainty of evidence was evaluated by the Grading of Recommendations Assessment, Development and Evaluation (GRADE) tool and the quality of systematic reviews/meta-analyses by the A MeaSurement Tool to Assess systematic Reviews 2 (AMSTAR2) tool.
RESULTS
Eleven studies accounting for 12 meta-analyses were included with a total of 4,586,515 patients. AMSTAR2 analysis showed a high quality in 1, moderate in 5, low in 2, and critically low in 3 studies. Digoxin was associated with an increased all-cause mortality (hazard ratio [HR] 1.19, 95% confidence interval [95%CI] 1.14-1.25) with moderate certainty of evidence and with an increased cardiovascular mortality (HR 1.19, 95%CI 1.06-1.33) with moderate certainty of evidence. Subgroup analysis showed that digoxin was associated with all-cause mortality both in patients with AF alone (HR 1.23, 95%CI 1.19-1.28) and in those with AF and HF (HR 1.14, 95%CI 1.12-1.16).
CONCLUSION
Data from this umbrella review suggests that digoxin use is associated with a moderate increased risk of all-cause and cardiovascular mortality in AF patients regardless of the presence of HF.
TRIAL REGISTRATION
This review was registered in PROSPERO (CRD42022325321).
Topics: Humans; Digoxin; Atrial Fibrillation; Anti-Arrhythmia Agents; Systematic Reviews as Topic; Heart Failure
PubMed: 36872367
DOI: 10.1007/s00228-023-03470-y -
American Journal of Therapeutics 2019
Topics: Adrenergic alpha-1 Receptor Agonists; Aged; Bradycardia; Digoxin; Drug Interactions; Electrocardiography; Glomerular Filtration Rate; Half-Life; Humans; Hypertension; Kidney; Male; Midodrine; Renal Insufficiency, Chronic; Tachycardia, Supraventricular
PubMed: 31498780
DOI: 10.1097/MJT.0000000000000856 -
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 -
Current Opinion in Cardiology Jan 2018Atrial fibrillation and heart failure are commonly encountered in current clinical practice. This review aims to revisit the complex interaction of these two common... (Review)
Review
PURPOSE OF REVIEW
Atrial fibrillation and heart failure are commonly encountered in current clinical practice. This review aims to revisit the complex interaction of these two common situations and the best treatment whenever both occurs, especially focusing on heart failure patients undergoing cardiac resynchronization therapy (CRT).
RECENT FINDINGS
It has been recently confirmed that in patients undergoing cardiac resynchronization therapy, 100% biventricular pacing percentage should be pursued. Large observational studies confirmed that atrioventricular junction ablation is very often the only way to gain 100% biventricular pacing in atrial fibrillation.
SUMMARY
On the basis of the recent observational extensive data, in patients presenting intermediate or elevated atrial tachycardia-atrial fibrillation burden, atrioventricular junction ablation may represent a fundamental tool to achieve full CRT delivery, thus, conferring marked improvements in global cardiac function, and by extension, in survival. Atrial fibrillation patients should not be excluded from CRT, provided that maximal biventricular pacing is warranted.
Topics: Adrenergic beta-Antagonists; Amiodarone; Anti-Arrhythmia Agents; Atrial Fibrillation; Atrioventricular Node; Cardiac Resynchronization Therapy; Catheter Ablation; Digoxin; Heart Failure; Humans; Treatment Outcome
PubMed: 29045344
DOI: 10.1097/HCO.0000000000000472 -
The American Journal of Cardiology Oct 2023Digoxin is used to treat atrial fibrillation and heart failure. Previous studies have reported an association between digoxin and higher mortality, but the results have...
Digoxin is used to treat atrial fibrillation and heart failure. Previous studies have reported an association between digoxin and higher mortality, but the results have been conflicting. This study assessed the association between digoxin use and all-cause mortality using comprehensive health data of patients treated for acute coronary syndrome (ACS). This was a retrospective analysis of 8,388 consecutive ACS patients treated in Tays Heart Hospital between 2007 and 2017, with a follow-up until the end of 2018. The adjusted Cox regression model was used to analyze the association between digoxin treatment and all-cause mortality with and without the inverse probability of treatment weighting (IPTW) method. IPTW was applied to estimate the residual confounding by the treatment selection. Clinical phenotype data were collected from various sources, including a prospectively updated online database maintained by physicians. The median follow-up time was 6.0 years (interquartile range 3.5 to 9.0 years). During the follow-up, 30.8% (n = 2,580) of the patients died. Altogether, 4.0% (n = 333) of the patients were treated with digoxin during hospitalization. In the Cox regression model, digoxin associated with increased mortality (age- and sex-adjusted hazard ratio [HR] 1.76 [1.51 to 2.05], p <0.001 and in the full risk factor-adjusted HR 1.23 [1.04 to 1.45], p = 0.016). The IPTW Cox analysis average treatment effect HR was 1.71 (1.12 to 2.62, p = 0.013), standardized average treatment effect HR was 1.35 (0.96 to 1.90, p = 0.082), and treatment effect among the treated HR was 1.32 (1.09 to 1.59, p = 0.004). In conclusion, digoxin treatment during ACS associates with increased mortality, despite adjusting for other risk factors and after accounting for factors explaining the residual confounding by selection bias.
Topics: Humans; Digoxin; Anti-Arrhythmia Agents; Retrospective Studies; Acute Coronary Syndrome; Atrial Fibrillation; Heart Failure
PubMed: 37573617
DOI: 10.1016/j.amjcard.2023.06.125 -
Pediatric Annals Oct 2015Atrial flutter (AFL) is the second most common type of tachyarrhythmia in the fetus and neonate. An atrial rate of 240 to 360 beats per minute, 2:1 atrioventricular...
Atrial flutter (AFL) is the second most common type of tachyarrhythmia in the fetus and neonate. An atrial rate of 240 to 360 beats per minute, 2:1 atrioventricular conduction, and a "saw tooth" appearance on electrocardiogram (ECG) are characteristic. On echocardiogram, bilateral atrial dilatation is the most common finding. Treatment is dependent on the severity of symptoms; delivery is usually indicated in the case of fetal heart failure or hydrops fetalis, whereas postnatal AFL is most commonly treated with direct current cardioversion (DCC). This article presents an illustrative case in which the patient presented antenatally via abnormal nonstress testing and subsequent fetal echocardiogram that was concerning for AFL. Postnatal ECG confirmed this diagnosis and the patient received DCC on the day of birth, followed by digoxin and propranolol as maintenance therapy.
Topics: Anti-Arrhythmia Agents; Atrial Flutter; Digoxin; Drug Therapy, Combination; Echocardiography; Electric Countershock; Electrocardiography; Female; Gestational Age; Humans; Infant, Newborn; Intensive Care Units, Neonatal; Pregnancy; Propranolol; Tachycardia
PubMed: 26473427
DOI: 10.3928/00904481-20151012-09 -
JAMA Network Open Jul 2023Serum creatinine-based estimated glomerular filtration rate (eGFRcr) may overestimate the glomerular filtration rate (GFR) in patients with cancer. Cystatin C-based eGFR...
IMPORTANCE
Serum creatinine-based estimated glomerular filtration rate (eGFRcr) may overestimate the glomerular filtration rate (GFR) in patients with cancer. Cystatin C-based eGFR (eGFRcys) is an alternative marker of GFR.
OBJECTIVE
To determine whether the therapeutic drug levels and adverse events (AEs) associated with renally cleared medications were higher in patients with cancer whose eGFRcys was more than 30% lower than their eGFRcr.
DESIGN, SETTING, AND PARTICIPANTS
This cohort study analyzed adult patients with cancer at 2 major academic cancer centers in Boston, Massachusetts. These patients had their creatinine and cystatin C measured on the same day between May 2010 and January 2022. The date of the first simultaneous eGFRcr and eGFRcys measurement was considered to be the baseline date.
EXPOSURE
The primary exposure was eGFR discordance, defined as an eGFRcys that was more than 30% lower than the eGFRcr.
MAIN OUTCOMES AND MEASURES
The primary outcome was risk of the following medication-related AEs within 90 days of the baseline date: (1) supratherapeutic vancomycin trough level greater than 30 μg/mL, (2) trimethoprim-sulfamethoxazole-related hyperkalemia (>5.5 mEq/L), (3) baclofen toxic effect, and (4) supratherapeutic digoxin level (>2.0 ng/mL). For the secondary outcome, a multivariable Cox proportional hazards regression model was used to compare 30-day survival of those with vs without eGFR discordance.
RESULTS
A total of 1869 adult patients with cancer (mean [SD] age, 66 [14] years; 948 males [51%]) had simultaneous eGFRcys and eGFRcr measurement. There were 543 patients (29%) with an eGFRcys that was more than 30% lower than their eGFRcr. Patients with an eGFRcys that was more than 30% lower than their eGFRcr were more likely to experience medication-related AEs compared with patients with concordant eGFRs (defined as eGFRcys within 30% of eGFRcr), including vancomycin levels greater than 30 μg/mL (43 of 179 [24%] vs 7 of 77 [9%]; P = .01), trimethoprim-sulfamethoxazole-related hyperkalemia (29 of 129 [22%] vs 11 of 92 [12%]; P = .07), baclofen toxic effects (5 of 19 [26%] vs 0 of 11; P = .19), and supratherapeutic digoxin levels (7 of 24 [29%] vs 0 of 10; P = .08). The adjusted odds ratio for vancomycin levels more than 30 μg/mL was 2.59 (95% CI, 1.08-7.03; P = .04). Patients with an eGFRcys more than 30% lower than their eGFRcr had an increased 30-day mortality (adjusted hazard ratio, 1.98; 95% CI, 1.26-3.11; P = .003).
CONCLUSIONS AND RELEVANCE
Results of this study suggest that among patients with cancer with simultaneous assessment of eGFRcys and eGFRcr, supratherapeutic drug levels and medication-related AEs occurred more commonly in those with an eGFRcys more than 30% lower than their eGFRcr. Future prospective studies are needed to improve and personalize GFR estimation and medication dosing in patients with cancer.
Topics: Male; Adult; Humans; Aged; Glomerular Filtration Rate; Creatinine; Cohort Studies; Cystatin C; Baclofen; Hyperkalemia; Trimethoprim, Sulfamethoxazole Drug Combination; Vancomycin; Digoxin; Neoplasms
PubMed: 37405775
DOI: 10.1001/jamanetworkopen.2023.21715 -
The American Journal of Medicine Dec 2020Digoxin reduces the risk of heart failure hospitalization but has no effect on mortality in patients with heart failure without atrial fibrillation in the randomized...
BACKGROUND
Digoxin reduces the risk of heart failure hospitalization but has no effect on mortality in patients with heart failure without atrial fibrillation in the randomized controlled trial setting. Observational studies of digoxin use in patients with atrial fibrillation have suggested a higher risk for poor outcomes. Less is known about this association in patients with heart failure and atrial fibrillation, the examination of which was the objective of the current study.
METHODS
We conducted an observational propensity score-matched study of predischarge digoxin initiation in 1768 hospitalized patients with heart failure and atrial fibrillation in the Medicare-linked Organized Program to Initiate Lifesaving Treatment in Hospitalized Patients with Heart Failure (OPTIMIZE-HF) registry, balanced on 56 baseline characteristics (mean age, 79 years; 55% women; 7% African American). Hazard ratios (HRs) and 95% confidence intervals (CIs) for outcomes were estimated for the 884 patients initiated on digoxin compared with 884 not initiated on digoxin.
RESULTS
HRs (95% CIs) for 30-day, 2-year, and 4-year all-cause mortality were 0.80 (0.55-1.18; P = .261), 0.94 (0.87-1.16; P = .936), and 1.01 (0.90-1.14; P = .729), respectively. Respective HRs (95% CIs) for heart failure readmission were 0.67 (0.49-0.92; P = .014), 0.81 (0.69-0.94; P = .005), and 0.85 (0.74-0.97; P = .022), and those for all-cause readmission were 0.78 (0.64-0.96; P = .016), 0.90 (0.81-1.00; P = .057), and 0.91 (0.83-1.01; P = .603). These associations were homogeneous between patients with left ventricular ejection fraction ≤45% vs >45%.
CONCLUSIONS
Among hospitalized older patients with heart failure (HFrEF and HFpEF) and atrial fibrillation, initiation of digoxin was associated with a lower risk of heart failure readmission but had no association with mortality.
Topics: Aged; Aged, 80 and over; Atrial Fibrillation; Cardiotonic Agents; Digoxin; Female; Heart Failure; Humans; Male; Retrospective Studies; Treatment Outcome
PubMed: 32603789
DOI: 10.1016/j.amjmed.2020.05.030 -
Cellular and Molecular Biology... Aug 2022Heart failure is one of the common cardiovascular diseases, and digoxin is required in the list of drug treatments. Considering the positive effect of this drug on heart...
Heart failure is one of the common cardiovascular diseases, and digoxin is required in the list of drug treatments. Considering the positive effect of this drug on heart failure, unfortunately, its therapeutic and toxic serum levels are different and very close to each other in different people. This study aimed to investigate the digoxin serum level in heart failure patients. For this purpose, we examined 32 patients with heart failure and digoxin users in this cross-sectional descriptive study. Some important factors involved in determining digoxin toxicity, such as age, gender, creatinine, creatinine clearance, cardiac output, urea, potassium, calcium, and digoxin levels, were measured. Statistical analysis showed that digoxin serum level increases with age (p<0.01). The increase in digoxin serum level was related to urea, creatinine, and potassium serum levels (p<0.01). In general, it seems that to prevent the increase of digoxin serum level and poisoning with it, it is necessary to continuously control the serum level of this drug in the form of serum measurement or according to its clearance.
Topics: Humans; Creatinine; Cross-Sectional Studies; Digoxin; Heart Failure; Potassium; Urea
PubMed: 36800827
DOI: 10.14715/cmb/2022.68.8.18 -
Journal of Molecular Recognition : JMR Oct 2021In this study, we presented elective, sensitive, and rapid UV-Vis spectrophotometry and calorimetric assay for the recognition of digoxin. Therefore, cysteamine-gold...
In this study, we presented elective, sensitive, and rapid UV-Vis spectrophotometry and calorimetric assay for the recognition of digoxin. Therefore, cysteamine-gold nanoparticles (Cys A-AuNPs) in the presence of cysteine acid amine and Silver nanoparticles in the presence of tetramethyl benzidine and hydrogen peroxide (AgNPs-TMB [3,3',5,5'-tetramethylbenzidine]-H O ) were synthesized and utilized as the desired probe. Finally, color variation of probes was observed in the absence and presence of digoxin. Obtained results indicate that the color of Cys A-AuNPs changed from dark pink to light in the absence and the presence of digoxin, respectively. Also, the color of AgNPs-TMB-H O changed from dark blue to light blue, in the absence and the presence of digoxin, respectively. Moreover, UV-Vis spectroscopies results indicate digoxin with a low limit of quantification of 0.125 ppm in human plasma samples which linear range was 0.125 to 11 ppm.
Topics: Benzidines; Colorimetry; Cysteamine; Digoxin; Gold; Humans; Hydrogen Peroxide; Limit of Detection; Metal Nanoparticles; Molecular Probes; Sensitivity and Specificity; Spectrophotometry, Ultraviolet
PubMed: 34106492
DOI: 10.1002/jmr.2917