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Frontiers in Cardiovascular Medicine 2023The current recommendations for monitoring digoxin, a narrow therapeutic index drug, are limited to confirming medication use or investigating suspicion of toxicity and... (Review)
Review
The current recommendations for monitoring digoxin, a narrow therapeutic index drug, are limited to confirming medication use or investigating suspicion of toxicity and fail our oath to do no harm. Numerous meta-analyses evaluating digoxin use consistently recommend frequent monitoring to maintain the level of 0.5 to ≤1.0 ng/ml because higher levels lead to increased morbidity and mortality without benefit. Data from the United States National Poison Control Center (2012-2020) show annual deaths due to digoxin of 18-36 compared to lithium's 1-7, and warfarin's 0-2 respectively. The latter drugs also have narrow therapeutic indexes like digoxin yet are more carefully monitored. Recognition of digoxin toxicity is impaired as levels are not being routinely checked after medications are added to a patient's regimen. In addition, providers may be using ranges to guide treatment that are no longer appropriate. It is imperative that monitoring guidelines and laboratory therapeutic levels are revised to reduce morbidity and mortality due to digoxin. In this review, we provide a comprehensive literature review of digoxin monitoring guidelines, digoxin toxicity, and evidence to support revising the ranges for serum digoxin monitoring.
PubMed: 37465455
DOI: 10.3389/fcvm.2023.1179892 -
Netherlands Heart Journal : Monthly... Feb 2024Digoxin-specific antibodies (digoxin-Fabs) are of value in the treatment of a strongly suspected or a known, potentially life-threatening digoxin toxicity. These... (Review)
Review
Digoxin-specific antibodies (digoxin-Fabs) are of value in the treatment of a strongly suspected or a known, potentially life-threatening digoxin toxicity. These antibodies are not registered for use in Europe; therefore Dutch hospital pharmacies are not allowed to keep them in stock. In the Netherlands, digoxin-Fabs are stored in a national calamity stock of emergency medicines at the National Institute for Public Health and the Environment. In the case of a medical emergency, digoxin-Fabs are available after contact with the Dutch Poisons Information Centre. Recent studies have shown that the dose of digoxin-Fabs required to effectively treat digoxin toxicity is lower than previously thought. In this article, we present the adjusted digoxin-Fab dosing strategy currently recommended by the Dutch Poisons Information Centre ( www.vergiftigingen.info ). This new dose titration strategy is safe and effective and has a cost-saving side-effect.
PubMed: 37861975
DOI: 10.1007/s12471-023-01814-y -
The Medical Letter on Drugs and... Jan 2024
Topics: Humans; Atrial Fibrillation
PubMed: 38180321
DOI: 10.58347/tml.2024.1693a -
Scientific Reports Sep 2023Cardiac rhythm regulated by micro-macroscopic structures of heart. Pacemaker abnormalities or disruptions in electrical conduction, lead to arrhythmic disorders may be...
Cardiac rhythm regulated by micro-macroscopic structures of heart. Pacemaker abnormalities or disruptions in electrical conduction, lead to arrhythmic disorders may be benign, typical, threatening, ultimately fatal, occurs in clinical practice, patients on digitalis, anaesthesia or acute myocardial infarction. Both traditional and genetic animal models are: In-vitro: Isolated ventricular Myocytes, Guinea pig papillary muscles, Patch-Clamp Experiments, Porcine Atrial Myocytes, Guinea pig ventricular myocytes, Guinea pig papillary muscle: action potential and refractory period, Langendorff technique, Arrhythmia by acetylcholine or potassium. Acquired arrhythmia disorders: Transverse Aortic Constriction, Myocardial Ischemia, Complete Heart Block and AV Node Ablation, Chronic Tachypacing, Inflammation, Metabolic and Drug-Induced Arrhythmia. In-Vivo: Chemically induced arrhythmia: Aconitine antagonism, Digoxin-induced arrhythmia, Strophanthin/ouabain-induced arrhythmia, Adrenaline-induced arrhythmia, and Calcium-induced arrhythmia. Electrically induced arrhythmia: Ventricular fibrillation electrical threshold, Arrhythmia through programmed electrical stimulation, sudden coronary death in dogs, Exercise ventricular fibrillation. Genetic Arrhythmia: Channelopathies, Calcium Release Deficiency Syndrome, Long QT Syndrome, Short QT Syndrome, Brugada Syndrome. Genetic with Structural Heart Disease: Arrhythmogenic Right Ventricular Cardiomyopathy/Dysplasia, Dilated Cardiomyopathy, Hypertrophic Cardiomyopathy, Atrial Fibrillation, Sick Sinus Syndrome, Atrioventricular Block, Preexcitation Syndrome. Arrhythmia in Pluripotent Stem Cell Cardiomyocytes. Conclusion: Both traditional and genetic, experimental models of cardiac arrhythmias' characteristics and significance help in development of new antiarrhythmic drugs.
Topics: Humans; Animals; Guinea Pigs; Dogs; Anti-Arrhythmia Agents; Ventricular Fibrillation; Calcium; Atrial Fibrillation; Papillary Muscles; Models, Animal
PubMed: 37775650
DOI: 10.1038/s41598-023-41942-4 -
JACC. Clinical Electrophysiology May 2024Some studies have shown digoxin use to be associated with adverse outcomes, including increased mortality. There are limited data on whether digoxin use is associated...
BACKGROUND
Some studies have shown digoxin use to be associated with adverse outcomes, including increased mortality. There are limited data on whether digoxin use is associated with increased risk of ventricular tachycardia/ventricular fibrillation (VT/VF) in heart failure patients with an implantable cardioverter-defibrillator (ICD).
OBJECTIVES
This study sought to assess whether digoxin use is associated with increased risk of VT/VF in patients with heart failure with reduced ejection fraction with a primary prevention ICD in landmark clinical trials.
METHODS
The study cohort consisted of patients with an ICD or cardiac resynchronization therapy-defibrillator who were enrolled in 4 landmark MADIT trials (Multicenter Automatic Defibrillator Implantation Trials). We employed propensity score quintile stratification for treatment with digoxin as well as additional multivariable adjustment to assess the risk of digoxin vs no-digoxin therapy for the endpoints of first and recurrent VT/VF and all-cause mortality. The proportional hazards regression models for arrhythmia-specific endpoints incorporated adjustments for the competing risk of death.
RESULTS
At baseline, 1,155 of 4,499 patients were on digoxin (26%). After propensity score quintile stratification, patients prescribed digoxin were shown to exhibit a statistically significant 48% increased risk of VT/VF (P < 0.001), 42% increased risk of the composite of VT/VF or death (P < 0.001), and a 37% increased risk of all-cause mortality (P = 0.006). Digoxin use was also associated with increased risk of appropriate ICD shocks (HR: 1.91; P < 0.001) and with increased burden of VT/VF events (HR: 1.46; P = 0.001).
CONCLUSIONS
Our findings suggests that digoxin use is associated with ventricular tachyarrhythmia and death in heart failure with reduced ejection fraction patients with an ICD.
PubMed: 38878014
DOI: 10.1016/j.jacep.2024.03.042 -
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 -
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 -
Current Problems in Cardiology Aug 2023The study evaluates the characteristics and trends of digoxin use during outpatient visits with atrial fibrillation in the US from 2006 to 2015.We conducted a... (Review)
Review
The study evaluates the characteristics and trends of digoxin use during outpatient visits with atrial fibrillation in the US from 2006 to 2015.We conducted a retrospective analysis of adult (age >/= 18) patient visits to office-based physicians from National Ambulatory Medical Care Survey (NAMCS) database between 2006-2015. The International Classification of Diseases, Ninth Revision, Clinical Modification codes were used to identify patients with Atrial fibrillation. Visits in which digoxin was listed as medication were analyzed with descriptive statistics. Multivariable logistic regression analysis was used to identify the predictors of usage of digoxin. Of a weighted sample of 108,113,894 patient visits, 17,617,853 (16.3%) visits included use of digoxin. Patients who used digoxin had a mean age of 75 ± 0.7 years and were predominantly Caucasian (92.56%). Among the patients who used digoxin, 24% had a diagnosis of heart failure. Multivariate analysis showed that the increased likelihood of digoxin utilization was associated with female sex (adjusted odds ratio (AOR) 1.34, 95% CI 1.05-1.71, p = .019), heart failure (aOR 1.51, 95% CI 1.05-1.17, p = .025), and usage of ³5 medications (aOR 5.32, 95% CI 3.67-7.71, p = <0.001). Among the visits with Atrial fibrillation, the percentage of visits with digoxin usage decreased from 23% in 2006 to 9% in 2013 and then again increased to 14% in 2015(P-trend <0.001). This is the first study to examine the use of digoxin in atrial fibrillation patients in a big outpatient setting. During 2006-2015, the percentage of digoxin prescriptions in atrial fibrillation patients has declined. Predictors of digoxin use in atrial fibrillation patients are female sex, congestive heart failure and higher number of concurrent medications.
Topics: Adult; Humans; Female; Aged; Male; Digoxin; Atrial Fibrillation; Retrospective Studies; Heart Failure; Health Care Surveys
PubMed: 35460684
DOI: 10.1016/j.cpcardiol.2022.101209 -
Tropical Doctor Oct 2023Effective therapy for patients with chronic cardiac failure (CCF) entails significant lifestyle modifications as well as often complex pharmaceutical regimes to... (Review)
Review
Effective therapy for patients with chronic cardiac failure (CCF) entails significant lifestyle modifications as well as often complex pharmaceutical regimes to alleviate symptoms, which, however, do not actually cure many patients. The gradual loss of cardiac function is impeded but not halted by such complicated pharmacological therapy, which primarily includes angiotensin-converting enzyme inhibitors, beta-blockers and diuretics, and sometimes digoxin, aspirin, warfarin, and anti-arrhythmic agents. Patients may be advised to track their weight and modify their diuretic prescription accordingly to avoid fluid overload or dehydration as part of the treatment plan. Non-pharmacologic treatment options are routinely integrated to improve the management of somatic complaints. Yoga and specialized breathing exercises seem to help CCF patients improve their cardiorespiratory and autonomic system function, and also their quality of life. We present the evidence.
Topics: Humans; Yoga; Quality of Life; Heart Failure; Angiotensin-Converting Enzyme Inhibitors; Breathing Exercises; Diuretics
PubMed: 37321800
DOI: 10.1177/00494755231180633 -
European Journal of Heart Failure Sep 2023To comprehensively assess hyponatraemia in acute heart failure (AHF) regarding prevalence, associations, hospital course, and post-discharge outcomes.
Hyponatraemia and changes in natraemia during hospitalization for acute heart failure and associations with in-hospital and long-term outcomes - from the ESC-HFA EORP Heart Failure Long-Term Registry.
AIMS
To comprehensively assess hyponatraemia in acute heart failure (AHF) regarding prevalence, associations, hospital course, and post-discharge outcomes.
METHODS AND RESULTS
Of 8298 patients in the European Society of Cardiology Heart Failure Long-Term Registry hospitalized for AHF with any ejection fraction, 20% presented with hyponatraemia (serum sodium <135 mmol/L). Independent predictors included lower systolic blood pressure, estimated glomerular filtration rate (eGFR) and haemoglobin, along with diabetes, hepatic disease, use of thiazide diuretics, mineralocorticoid receptor antagonists, digoxin, higher doses of loop diuretics, and non-use of angiotensin-converting enzyme inhibitors/angiotensin receptor blockers and beta-blockers. In-hospital death occurred in 3.3%. The prevalence of hyponatraemia and in-hospital mortality with different combinations were: 9% hyponatraemia both at admission and discharge (hyponatraemia Yes/Yes, in-hospital mortality 6.9%), 11% Yes/No (in-hospital mortality 4.9%), 8% No/Yes (in-hospital mortality 4.7%), and 72% No/No (in-hospital mortality 2.4%). Correction of hyponatraemia was associated with improvement in eGFR. In-hospital development of hyponatraemia was associated with greater diuretic use and worsening eGFR but also more effective decongestion. Among hospital survivors, 12-month mortality was 19% and adjusted hazard ratios (95% confidence intervals) were for hyponatraemia Yes/Yes 1.60 (1.35-1.89), Yes/No 1.35 (1.14-1.59), and No/Yes 1.18 (0.96-1.45). For death or heart failure hospitalization they were 1.38 (1.21-1.58), 1.17 (1.02-1.33), and 1.09 (0.93-1.27), respectively.
CONCLUSION
Among patients with AHF, 20% had hyponatraemia at admission, which was associated with more advanced heart failure and normalized in half of patients during hospitalization. Admission hyponatraemia (possibly dilutional), especially if it did not resolve, was associated with worse in-hospital and post-discharge outcomes. Hyponatraemia developing during hospitalization (possibly depletional) was associated with lower risk.
Topics: Humans; Hyponatremia; Heart Failure; Hospital Mortality; Aftercare; Patient Discharge; Hospitalization; Hospitals; Registries
PubMed: 37114294
DOI: 10.1002/ejhf.2873