From Pregnancy Pains to Paralysis: An Erroneous Intrathecal Digoxin Administration Case Report and Review of Medical Errors.

Digoxin is a Na-K ATPase inhibitor commonly used to treat heart failure and atrial fibrillation. It is only approved for oral or intravenous (IV) use. There is no approved indication for intrathecal administration. Only four previously reported cases of intrathecal digoxin administration in pregnant patients are in the literature. We present a patient who had an unfortunate case of erroneous intrathecal Digoxin administration following an elective Cesarean section. Post-delivery, the patient's mental status deteriorated. She became unresponsive and remained comatose for 11 days. Brain magnetic resonance imaging (MRI) showed diffuse, patchy hyperintensities involving bilateral frontotemporal lobes and basal ganglia. A spine MRI showed extensive cervical and thoracic cord edema. At discharge, the patient was paraplegic with no sensation or motor response below the level of T10. At the 90-day follow-up, she had intact mental status and minimal improvement in motor strength and sensation below T10 and was reportedly breastfeeding. This is an unfortunate case of severe neurological deficits resulting from a grave medical error, which continues to be a prevalent issue in the United States healthcare system.

Repurposing cardiac glycosides for anticancer treatment: a review of clinical studies.

Cardiac glycosides (CGs), which are traditionally used for heart disease, show promise for cancer therapy. However, there is a lack of a comprehensive review of clinical studies in this area, and so far, CGs have not been widely integrated into clinical cancer treatment. This review covers clinical studies from the past five years, highlighting the potential of CGs to reduce cancer risk, enhance chemotherapy effectiveness, mitigate chemotherapy-induced side effects and improve quality of life. Future clinical trials should personalize the dosage of CGs, integrate molecular testing and investigate immunogenic cell death induction and the potential of CGs for treating bone cancer and metastasis. Optimizing the repurposing of CGs for anticancer treatment requires consideration of specific CGs, cancer types and concurrent medications.

Incidence of All-Cause, Cardiovascular, and Atrial Fibrillation-Related Hospitalizations: Focus on Antiarrhythmic Drugs.

Background: Atrial fibrillation (AF) is associated with an increased risk of hospital admission, but few data on reasons for hospitalization and on the role of anti-arrhythmic drugs are available. Objectives: The purpose of this study was to investigate the incidence rate and factors associated with all-cause, cardiovascular, and AF-related hospitalizations. Methods: Prospective ongoing ATHERO-AF (Atherosclerosis in Atrial Fibrillation) cohort study enrolling AF patients on oral anticoagulants. Primary end points were all-cause, cardiovascular, and AF-related hospitalization, the latter defined as AF recurrences for paroxysmal AF and high-rate symptomatic AF episodes for persistent/permanent AF patients. Results: 2,782 patients were included (43.5% female; mean age was 74.6 ± 9.1 years). During a mean follow-up of 31 ± 26.8 months, 1,205 (12.1%/year) all-cause, 533 cardiac (5.7%/year), and 180 (2.0%/year) AF-related hospitalizations occurred. Predictors of AF-related hospitalizations were the use of flecainide/propafenone in both paroxysmal and persistent/permanent AF patients (HR: 1.861; 95% CI: 1.116 to 3.101 and 1.947; 95% CI: 1.069 to 3.548, respectively). Amiodarone (HR: 3.012; 95% CI: 1.835-4.943), verapamil/diltiazem (HR: 2.067; 95% CI: 1.117-3.825), and cancer (HR: 1.802; 95% CI: 1.057-3.070) but not beta-blockers and digoxin were associated with an increased risk of AF-related hospitalizations in persistent/permanent AF patients. Conclusions: Elderly AF patients frequently undergo hospitalizations for both cardiovascular and noncardiovascular causes. The use of anti-arrhythmic drugs was associated with an increased risk of AF-related hospitalization suggesting a scarce effect of these drugs in preventing AF episodes. Therefore, their use should be carefully considered and reserved for symptomatic patients with frequent AF recurrences.

Effect of midostaurin on the pharmacokinetics of P-gp, BCRP, and CYP2D6 substrates: assessing potential drug-drug interactions in healthy participants : Brief title: Drug-drug interaction of midostaurin.

PURPOSE: Midostaurin, approved for FLT3-mutated acute myeloid leukemia and advanced systemic mastocytosis, is mainly metabolized by cytochrome P450 (CYP) 3A4. Midostaurin exhibited potential inhibitory effects on P-glycoprotein (P-gp), breast cancer resistance protein (BCRP), organic anion-transporting polyprotein 1B1, and CYP2D6 in in vitro studies. This study investigated the pharmacokinetic (PK) effects of midostaurin on P-gp (digoxin), BCRP (rosuvastatin) and CYP2D6 (dextromethorphan) substrates in healthy adults. METHODS: This was an open-label, single-sequence, phase I clinical study evaluating the effect of single-dose midostaurin (100 mg) on the PK of digoxin and rosuvastatin (Arm 1), and dextromethorphan (Arm 2). Participants were followed up for safety 30 days after last dose. In addition, the effect of midostaurin on the PK of dextromethorphan metabolite (dextrorphan) was assessed in participants with functional CYP2D6 genes in Arm 2. RESULTS: The effect of midostaurin on digoxin was minor and resulted in total exposure (AUC) and peak plasma concentration (Cmax) that were only 20% higher. The effect on rosuvastatin was mild and led to an increase in AUCs of approximately 37-48% and of 100% in Cmax. There was no increase in the primary PK parameters (AUCs and Cmax) of dextromethorphan in the presence of midostaurin. The study treatments were very well tolerated with no occurance of severe adverse events (AEs), AEs of grade ≥ 2, or deaths. CONCLUSION: Midostaurin showed only a minor inhibitory effect on P-gp, a mild inhibitory effect on BCRP, and no inhibitory effect on CYP2D6. Study treatments were well tolerated in healthy adults.

Bidirectional ventricular tachycardia due to digoxin-diuretic interaction in post-cardiac surgery patient: a case report.

Bidirectional ventricular tachycardia (BVT) is a rare form of malignant ventricular arrhythmia characterized by beat-to-beat alternation in the QRS axis. BVT is a hallmark of digitalis toxicity, but digoxin-induced BVT secondary to digoxin-diuretic interaction in cardiac surgery patients is not widely reported. We present the case of a 62-year-old woman undergoing mitral valve replacement with tricuspid annuloplasty who developed postoperative congestive heart failure and vasoplegic syndrome requiring norepinephrine, vasopressin, and loop diuretics. During postoperative care, she presented atrial fibrillation with rapid ventricular response, achieving rate control with digoxin, but later displayed hemodynamically stable BVT associated with digitalis toxicity. The case highlights the importance of physicians monitoring digoxin toxicity when prescribing digoxin to patients with a diuretic regimen, particularly loop diuretics. During digoxin-induced-BVT, supportive treatment, including discontinuing digitalis coupled with potassium and magnesium supplements, can be considered as long as digoxin-specific antibodies are unavailable, and the patient is hemodynamically stable.

La taquicardia ventricular bidireccional (TVB) es una arritmia rara caracterizada por alternancia latido a latido en el eje QRS. La TVB es característica de intoxicación digitálica; sin embargo, la TVB secundaria a interacción digoxina-diurético en pacientes posoperados de cirugía cardíaca no se ha reportado ampliamente. Presentamos el caso de una mujer de 62 años sometida a cirugía cardiaca que desarrolló falla cardiaca congestiva y síndrome vasopléjico en el posoperatorio por lo que requirió noradrenalina, vasopresina y diurético de asa. Durante la hospitalización presentó fibrilación auricular con respuesta ventricular rápida; se logró control con digoxina, pero posteriormente presentó TVB asociada a intoxicación digitálica. Este caso resalta la importancia de detectar intoxicación digitálica durante la prescripción de digoxina a pacientes con un régimen diurético, especialmente diuréticos de asa. Durante la TVB inducida por digoxina, el tratamiento de soporte se puede considerar cuando no haya disponible anticuerpos específicos para digoxina y el paciente este hemodinámicamente estable.

Antidote use for cardiac arrest or hemodynamic instability due to cardiac glycoside poisoning: A narrative review.

Introduction: Cardiac glycosides comprise medications such as digoxin and digitoxin, plants, and even certain toad venoms. Intoxication with cardiac glycosides can lead to hemodynamic instability and cardiac arrest. With this narrative review, our objective was to determine if any therapy used in a near-cardiac arrest state due to cardiac glycoside poisoning could improve survival with favourable functional and neurological outcomes. Methods: We searched the Medline, PubMed, EMBASE and Cochrane Library databases up to February 2022 for controlled trials, observational studies, and case reports. We reviewed studies if participants were exposed to a cardiac glycoside, had hemodynamic instability, and an intervention was attempted to reverse the toxicity. The effect of interventions on (1) survival with favourable functional and neurological outcomes and (2) correction of hemodynamic instability was assessed. Results: Of the 2422 studies found, 73 were included for analysis, of which 58 were case reports or series, and 15 were observational cohorts. Most patients were intoxicated with medication (60 individual cases and 11 observational cohorts). Administration of digoxin immune-Fab fragments was associated with improved hemodynamic status and survival in medication patients. Administration of magnesium, cardioversion, and cardiac pacing was associated with favourable outcomes, while administration of atropine, antiarrhythmics, or calcium was not. Conclusion: In patients with hemodynamic instability due to cardiac glycoside intoxication, digoxin immune-Fab fragments should be given, and magnesium administration, cardioversion, and cardiac pacing can reasonably be attempted.

"Cardiac glycosides"-quo vaditis?-past, present, and future?

Up to date, digitalis glycosides, also known as "cardiac glycosides", are inhibitors of the Na+/K+-ATPase. They have a long-standing history as drugs used in patients suffering from heart failure and atrial fibrillation despite their well-known narrow therapeutic range and the intensive discussions on their raison d'être for these indications. This article will review the history and key findings in basic and clinical research as well as potentially overseen pros and cons of these drugs.

Digoxin treatment does not reinduce radioiodine uptake in radioiodine refractory non-medullary thyroid carcinoma.

Objective: Patients with non-medullary thyroid carcinoma (NMTC) that are refractory to radioactive iodine (RAI) have a poor prognosis. Strategies for restoring the ability to take up iodine, so-called redifferentiation, are promising but not suitable for all patients. Preclinical studies, in human cell lines just as in a murine model, have shown that the cardiac glycoside digoxin restored RAI uptake. This prospective single-center open-label study aimed to investigate whether treatment with digoxin could reinduce clinically relevant RAI uptake in patients with metastasized RAI-refractory NMTC. Methods: Eight patients with metastasized RAI-refractory NMTC were included between November 2022 and June 2023. Before treatment, a baseline [123I]NaI scintigraphy was performed. Thereafter, patients were treated with digoxin for 3 weeks. Starting doses depended on age and weight. For safety reasons, the usual therapeutic range was aimed for. After 1 week, the digoxin plasma concentration was measured, and the digoxin dose was adjusted if necessary. After 3 weeks of digoxin treatment, a second [123I]NaI scintigraphy was performed. RAI uptake was compared between the two scintigraphies. Results: Seven patients completed the digoxin treatment and were evaluable. None of the seven patients showed clinically relevant RAI uptake after digoxin treatment. No digoxin-related serious adverse events occurred during this trial. Conclusion: Contrary to results from preclinical trials, in this trial, 3 weeks of digoxin treatment did not reinduce RAI uptake in patients with NMTC. This highlights essential challenges regarding the approach toward optimization of studies aimed to restore the RAI uptake and its therapeutic efficacy through drug repurposing.

Not only Van Gogh: a case of BRASH syndrome with concomitant digoxin toxicity.

BACKGROUND: Bradycardia, renal failure, atrioventricular (AV) node blocking, shock, and hyperkalemia syndrome is a potentially life-threatening clinical condition characterized by bradycardia, renal failure, atrioventricular (AV) node blocking, shock, and hyperkalemia. It constitutes a vicious circle in which the accumulation of pharmacologically active compounds and hyperkalemia lead to hemodynamic instability and heart failure. CASE PRESENTATION: A 66-year-old Caucasian female patient was admitted to the emergency department presenting with fatigue and bradycardia. Upon examination, the patient was found to be anuric and hypotensive. Laboratory investigations revealed metabolic acidosis and hyperkalemia. Clinical evaluation suggested signs of digoxin toxicity, with serum digoxin concentrations persistently elevated over several days. Despite the implementation of antikalemic measures, the patient's condition remained refractory, necessitating renal dialysis and administration of digoxin immune fab. CONCLUSION: Bradycardia, renal failure, atrioventricular (AV) node blocking, shock, and hyperkalemia syndrome is a life-threatening condition that requires prompt management. It is important to also consider potential coexisting clinical manifestations indicative of intoxication from other pharmacological agents. Specifically, symptoms associated with the accumulation of drugs eliminated via the kidneys, such as digoxin. These manifestations may warrant targeted therapeutic measures.

The NOS1AP gene rs10494366 common genetic variant does not modify the risk of sudden cardiac death in users of digoxin.

AIMS: Common genetic variations in the nitric oxide synthase-1 adaptor protein (NOS1AP) gene are associated with QT-interval prolongation. In a previous study, we observed an association between the rs10494366 variant of this gene and an increased QT-interval shortening in digoxin users. As QT-interval shortening is a risk factor for sudden cardiac death (SCD), in this study, we investigated whether the association between digoxin use and risk of SCD differs in participants with different NOS1AP rs10494366 genotypes. METHODS: We included 11 377 individuals from the prospective population-based cohort of the Rotterdam Study. We used Cox proportional hazard regression analysis with digoxin as time-dependent exposure to estimate the associations between current digoxin use and the risk of SCD among different rs10494366 genotype groups in the adjusted models. We also studied whether such an association was dose-dependent, comparing high dosage (≥ 0.250 mg), moderate dosage (0.125 mg ≤ dose< 0.250 mg) and low dosage (< 0.125 mg) digoxin users with non-users. RESULTS: The median baseline age of the total study population was 62 (interquartile range [IQR] 58-71) years. The cumulative incidence of SCD was 4.1% (469 cases), and among them, 74 (15.7%) individuals were current digoxin users at the time of death, during a median follow-up of 11.5 (IQR 6.5-17) years. Current digoxin users had an increased risk of SCD (multivariable adjusted model hazard ratio [HR]: 3.07; 95% confidence interval [CI]: 2.38-3.98), with no significant differences between the three genotype groups. The adjusted HRs were 4.03 [95% CI: 1.98-8.21] in the minor homozygous GG, 3.46 [95% CI: 2.37-5.04] in the heterozygous TG and 2.56 [95%CI: 1.70-3.86] in the homozygous TT genotype groups. Compared to low- and moderate-dose, high-dose digoxin users with GG genotype had the highest risk of SCD (HR: 5.61 [95% CI: 1.34-23.47]). CONCLUSIONS: Current use of digoxin is associated with a significantly increased risk of SCD. The NOS1AP gene rs10494366 variant did not modify the digoxin-associated risk of SCD in a population of European ancestry.

Intralesional combined digoxin and furosemide versus intralesional 5-flurouracil for the treatment of recalcitrant plantar warts: a prospective, randomized study.

There are many therapeutic modalities for plantar warts, however treating it remains challenging. Intralesional injection of 5-fluorouarcil and combined digoxin and furosemide were observed to be effective and safe, however no comparison study between them was done. Our study was conducted to evaluate the efficacy of both therapies in the treatment of plantar warts. 90 adult patients with multiple recalcitrant plantar warts were included in our study. They were randomly allocated to one of three groups; combined digoxin and furosemide, 5-fluorouarcil, or normal saline group. Fortnightly injections were done into all studied warts till complete clearance or up to 5 sessions. Warts were evaluated clinically and dermoscopically. Clinical response was reported in 24 patients (80%) of the combined digoxin and furosemide group with 40% complete response and in 24 patients (80%) of the 5-fluorouarcil group with 33.3% complete response. No statistically significant difference was observed between the two groups concerning efficacy and safety. Intralesional injection of 5-fluorouarcil and combined digoxin and furosemide are nearly equivalent in efficacy and safety for plantar wart treatment. Dermoscopy helps to take the truthful judgment about complete clearance of warts.

Digoxin and Risk of Ventricular Tachyarrhythmia and Death in ICD Recipients.

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.

Clinical Impact of Digitalis Therapy in a Large Multicenter Cohort of CRT-Recipients.

(1) Introduction: Digitalis use in patients with severe heart failure is controversial. We assessed the effects of digitalis therapy on mortality in a large, observational study in recipients of cardiac resynchronization therapy (CRT). (2) Methods: Consecutive patients receiving a CRT-defibrillator in three European tertiary referral centers were enrolled and followed-up for a mean 37 months ± 28 months. Digitalis use was assessed at the time of CRT implantation. A multivariate Cox-regression model and propensity score matching were used to determine all-cause mortality as the primary endpoint. CRT-response (defined as improvement of ≥1 NYHA class), echocardiographic improvement (defined as improvement of LVEF of ≥ 5%) and incidence of ICD shocks and rehospitalization were assessed as secondary endpoints in a subgroup of patients. (3) Results: The study comprised 552 CRT-recipients with standard indications, including 219 patients (40%) treated with digitalis. Compared to patients without digitalis, they had more often atrial fibrillation, poorer LVEF and a higher NYHA class (all p ≤ 0.002). Crude analysis of all-cause mortality demonstrated a similar relative risk of death for patients with and without digitalis (HR = 1.14; 95% CI 0.88-1.5; p = 0.40). After adjustment for independent predictors of mortality, digitalis therapy did not alter the risk for death (adjusted HR = 1.04; 95% CI 0.75-1.45; p = 0.82). Furthermore, in comparison to 286 propensity-score-matched patients, mortality was not affected by digitalis intake (propensity-adjusted HR = 1.11; 95% CI 0.72-1.70; p = 0.64). A CRT-response was predominant in digitalis non-users, concerning both improvement of HF symptoms and LVEF (NYHA p < 0.01; LVEF p < 0.01), while patients on digitalis had more often ventricular tachyarrhythmias requiring ICD shock (p = 0.01); although, rehospitalization for cardiac reasons was significantly lower among digitalis users compared to digitalis non-users (HR = 0.58; 95% C. I. 0.40-0.85; p = 0.01). (4) Conclusions: Digitalis therapy had no effect on mortality, but was associated with a reduced response to CRT and increased susceptibility to ventricular arrhythmias requiring ICD shock treatment. Although, digitalis administration positively altered the likelihood for cardiac rehospitalization during follow-up.

Thirty-day risk of digoxin toxicity among older adults co-prescribed trimethoprim-sulfamethoxazole versus amoxicillin: A population-based cohort study.

IMPORTANCE: Trimethoprim-sulfamethoxazole (TMP-SMX) may increase digoxin concentration, a medication with a narrow therapeutic index. Small changes in digoxin concentration could predispose individuals to the risk of toxicity. OBJECTIVE: To characterize the risk of digoxin toxicity in older adults taking digoxin following co-prescription of TMP-SMX compared with co-prescription of amoxicillin. DESIGN, SETTINGS, AND PARTICIPANTS: Retrospective population-based cohort study in Ontario, Canada (2002-2020) using linked health care data. Participants comprised 47,961 older adults taking digoxin (58% women; median age 80 years [interquartile range 74-86]) who were newly treated with TMP-SMX (n = 10,273) compared with those newly treated with amoxicillin (n = 37,688). EXPOSURE: Co-prescription of TMP-SMX versus amoxicillin in older adults concurrently taking digoxin. MAIN OUTCOME AND MEASURE: The primary outcome was a hospital encounter (i.e., hospital admission or emergency department visit) with digoxin toxicity within 30 days of the antibiotic prescription. Inverse probability of treatment weighting on the propensity score was used to balance comparison groups on indicators of baseline health. Weighted risk ratios (RR) were obtained using modified Poisson regression and weighted risk differences (RD) using binomial regression. The number needed to harm (NNH) was calculated as 1/RD. RESULTS: A hospital encounter with digoxin toxicity occurred in 49/10,273 (0.48%) patients treated with TMP-SMX versus 32/37,688 (0.08%) in those treated with amoxicillin (weighted RR, 5.71 [95% confidence interval (CI), 3.19 to 10.24]; weighted RD, 0.39% [95% CI, 0.25% to 0.53%]; NNH 256 [95% CI, 233 to 400]). CONCLUSION AND RELEVANCE: In older adults taking digoxin, the 30-day risk of a hospital encounter with digoxin toxicity was nearly 6 times higher in those co-prescribed TMP-SMX versus amoxicillin, although the absolute risk difference was low (0.4%). Physicians should prescribe an alternative antibiotic when clinically appropriate. If TMP-SMX must be co-prescribed with digoxin (if the benefit is believed to outweigh the risk), digoxin should be dose-reduced on an individual basis.

Identification and characterization of critical values in therapeutic drug monitoring: a retrospective analysis.

Therapeutic drug monitoring (TDM) is a crucial clinical practice that improves pharmacological effectiveness and prevent severe drug-related adverse events. Timely reporting and intervention of critical values during TDM are essential for patient safety. In this study, we retrospectively analyzed the laboratory data to provide an overview of the incidence, distribution pattern and biochemical correlates of critical values during TDM. A total of 19,110 samples were tested for nine drug concentrations between January 1, 2019, and December 31, 2020. Of these, 241 critical values were identified in 165 patients. The most common critical values were vancomycin trough (63.4%), followed by tacrolimus trough (16.9%) and digoxin (15.2%). The primary sources of drug critical values were the department of general intensive care unit (ICU), cardiology, and surgery ICU. At baseline or the time of critical value, significant differences were found between the vancomycin, digoxin, and tacrolimus groups in terms of blood urea nitrogen (BUN), creatinine, N-terminal Pro-B-Type Natriuretic Peptide (NT-proBNP), and lymphocyte percentage, P < 0.05. Therefore, it is important to prioritize and closely monitor drug concentrations to reduce laboratory critical values during TDM.

Combination therapy of beta-blockers and digoxin is associated with increased risk of major adverse cardiovascular events and all-cause mortality in patients with atrial fibrillation: a report from the GLORIA-AF registry.

The effect of digoxin and beta-blockers on cardiovascular outcomes and mortality remains unclear. The study aimed to determine differences in cardiovascular (CV) outcomes and death rates among patients with atrial fibrillation (AF) who were prescribed with beta-blockers, digoxin or combination therapy. Data from phase II/III of the prospective Global Registry on Long-Term Oral Anti-thrombotic Treatment in Patients with Atrial Fibrillation (GLORIA-AF) were analysed. The risk of major cardiovascular events (MACE) and death among patients with different prescriptions using COX proportional hazard regression was considered. Propensity score (PS) matching and weighting were further used to adjust for potential confounders of prescription use. A total of 14,201 patients [median age: 71.0 (IQR 64.0-77.0) years; 46.2% female] were recruited. After a median follow-up of 3.0 (IQR 2.4-3.1) years, 864 MACE, and 988 all-cause deaths were recorded. The incidence rate (IR) of MACE was 22.4 (95%CI 21.0-24.0) per 1000 person-years, while the IR of all-cause death was 25.4 (95%CI 23.8-27.0) per 1000 person-years. After multivariate adjustment with Cox regression, the risk of MACE (HR 1.35, 95% CI 1.09-1.68) and the risk of all-cause death (HR 1.28, 95%CI 1.04-1.57) were significantly higher in the combination therapy group, compared to the beta-blockers alone group. The risks of MACE and all-cause death remained significant in both PS matched and PS weighted cohort Among AF patients, combination therapy of beta-blockers and digoxin was associated with higher risks of MACE and all-cause death compared to beta-blockers alone.

Seven- and thirty-day mortality in digoxin poisoning: Results from the DIGITOX study.

BACKGROUND: Digoxin poisonings are relatively common and potentially fatal, requiring immediate therapeutic intervention, with special attention to the patient's hemodynamic status and the presence of electrocardiographic and electrolytic disturbances. OBJECTIVE: To identify factors associated with seven-day and thirty-day mortality in digoxin poisoning. DESIGN, SETTINGS AND PARTICIPANTS: A retrospective, observational, multicenter study was conducted across 15 Hospital Emergency Departments (HED) in Spain. All patients over 18 years of age who presented to participating HEDs from 2015 to 2021 were included. The inclusion criteria encompassed individuals meeting the criteria for digoxin poisoning, whether acute or chronic. OUTCOMES MEASURE AND ANALYSIS: To identify independent factors associated with 7-day and 30-day mortality, a multivariate analysis was conducted. This analysis included variables of clinical significance, as well as those exhibiting a trend (p < 0.1) or significance in the bivariate analysis. MAIN FINDINGS: A total of 658 cases of digoxin poisoning were identified. Mortality rates were 4.5% (30 patients) at seven days and 11.1% (73 patients) at thirty days. Regarding 7-day mortality, the mean age of deceased patients was comparable to survivors (84.7 (8.9) vs 83.9 (7.9) years; p = ns). The multivariate analysis revealed that factors independently associated with 7-day mortality encompassed the extent of dependence assessed by the Barthel Index (BI 60-89 OR 0.28; 95% CI 0.10-0.77; p = 0.014 and BI>90 OR 0.22; 95% CI 0.08-0.63; p = 0.005), the identification of ventricular arrhythmias (OR 1.34; 95% CI 1.34-25.21; p = 0.019), and the presence of circulatory (OR 2.84; 95% CI 1.19-6.27; p = 0.019) and neurological manifestations (OR 2.67; 95% CI 1.13-6.27; p = 0.025). Factors independently associated with 30-day mortality encompassed extent of dependence (BI 60-89 OR 0.37; 95% CI 0.20-0.71; p = 0.003 and BI>90 OR 0.18; 95% CI 0.09-0.39; p < 0.001) and the identification of circulatory (OR 2.13; 95% CI 1.10-4.15; p = 0.025) and neurological manifestations (OR 2.39; 95% CI 1.25-3.89; p = 0.006). CONCLUSIONS: The study identifies the degree of dependency assessed by the Barthel Index and the presence of cardiovascular and neurological symptoms as independent predictors of both 7-day and 30-day mortality. Additionally, the detection of ventricular arrhythmia is also an independent factor for 7-day mortality.

A Comprehensive Review on Unveiling the Journey of Digoxin: Past, Present, and Future Perspectives.

Digoxin, a cardiac glycoside derived from the foxglove plant (Digitalis spp.), has been utilized for centuries in managing various cardiac conditions due to its ability to increase myocardial contractility and regulate heart rate. This comprehensive review explores the historical context, pharmacological properties, clinical applications, efficacy, safety profile, challenges, and future perspectives of digoxin. Tracing its journey from traditional medicine to modern cardiovascular therapeutics, we delve into its mechanism of action, therapeutic indications, and clinical guidelines. While digoxin remains a cornerstone therapy for heart failure and atrial fibrillation, its narrow therapeutic index and individual variability in response pose challenges in clinical practice. Nevertheless, ongoing research efforts aim to elucidate its role in emerging therapeutic areas and technological advancements in drug delivery. Despite the advent of newer pharmacological agents, digoxin's enduring relevance lies in its established efficacy, affordability, and global accessibility. This review underscores the symbiotic relationship between tradition and progress in cardiovascular medicine, highlighting the timeless pursuit of medical innovation to optimize patient care.