Serum Digoxin Concentration Research Articles

Intermittent low-dose digoxin may be effective and safe in patients with chronic heart failure undergoing maintenance hemodialysis.

A low dose of digoxin is known to reduce mortality and hospitalization in patients with heart failure; however, the safety of digoxin in treating patients with heart failure on maintenance hemodialysis remains controversial. The objective of this study was to determine the effectiveness and safety of digoxin at lower doses in patients with heart failure on maintenance hemodialysis using a retrospective cohort study. This study included 67 heart-failure patients on maintenance hemodialysis: Twenty-four patients received intermittent low doses of digoxin (ILDD), 23 patients received continuous low doses of digoxin (CLDD) and the remaining patients were used as a control group without digoxin treatment. The brain natriuretic peptide (BNP) level and serum digoxin concentrations (SDCs) were measured by ELISA and the changes in left ventricular end diastolic diameter (LVEDD), left ventricular ejection fraction (LVEF), cardiac output (CO) and heart rate (HR) were evaluated by two-dimensional echocardiography. The symptoms of digoxin toxicity were monitored in the treated patients. Compared with the control group, LVEDD, BNP and HR decreased significantly between days 0 and 60 in the ILDD and CLDD groups, but LVEF and CO increased between days 0 and 60 in the same groups (all P<0.05). The levels of BNP and the LVEDD, CO, LVEF and HR were not significantly different between the ILDD and CLDD groups (P>0.05). Furthermore, and the mean SDC of the ILDD group was lower than that of the CLDD group. In the ILDD group, no patients had apparent symptoms of toxicity, but four patients developed digoxin toxicity in the CLDD group. In conclusion an intermittent lower dose of digoxin has beneficial effects and clinical safety in hemodialysis patients with congestive heart failure.

Use of a simplified nomogram to individualize digoxin dosing versus standard dosing practices in patients with heart failure.

To compare the frequency of achieving a therapeutic serum digoxin concentration (SDC), defined as 0.5-0.9 ng/ml, by using a simplified nomogram to individualize digoxin dosing with standard dosing practices in patients with heart failure, and to characterize the relationship between genetic polymorphisms of the ABCB1 gene and SDC. Prospective study with a historical control group. Outpatient care center of an urban academic medical center. A total of 131 adults with heart failure due to left ventricular dysfunction who were treated with digoxin. Digoxin doses were determined either by the dosing nomogram (65 patients) or standard care (SC; 66 patients) by using historical controls who were randomly selected from a list of SDCs obtained from laboratory records and who had their digoxin doses determined by standard dosing practices. The primary end point was the proportion of patients achieving a steady-state SDC of 0.5-0.9 ng/ml; secondary end points were mean SDC and proportion of patients achieving a steady-state SDC lower than 1.0 ng/ml. Postdistributive steady-state SDCs were measured 2-4 weeks after digoxin dosage adjustment or initiation. Therapeutic SDCs were achieved with similar frequency in both groups (38.7% in the nomogram group vs 34.5% in the SC group, p=0.65); however, more patients in the nomogram group had SDCs lower than 1.0 ng/ml than in the SC group (85.0% vs 44.9%, p<0.001). Mean daily digoxin doses were lower in the nomogram group (149 ± 67 μg vs 177 ± 74 μg, p=0.02), resulting in lower mean SDCs compared with those in the SC group (0.52 ± 0.30 ng/ml vs 1.12 ± 0.58 ng/ml, p<0.001). Patients in the pharmacogenetic substudy provided blood samples for genotyping of three common ABCB1 single nucleotide polymorphisms: C1236T (rs1128503), G2677T/A (rs2032582), and C3435T (rs1045642). SDCs were not significantly associated with ABCB1 genotypes. Our simplified digoxin dosing nomogram resulted in lower SDCs compared with standard dosing practices but achieved therapeutic SDCs with similar frequency. A greater proportion of patients dosed according to our nomogram had SDCs lower than 1.0 ng/ml, consistent with consensus guidelines. Genetic polymorphisms of the ABCB1 gene were not associated with SDC.

Efficiency of individual dosage of digoxin with calculated concentration.

BackgroundDigoxin is a frequently prescribed drug, particularly in the elderly population, in which there is an increased prevalence of atrial fibrillation and cardiac failure. With its complex pharmacokinetic profile and narrow therapeutic index, use of digoxin requires regular monitoring of blood levels. Recent evidence suggests that a lower concentration range (0.4–1.0 ng/mL) is preferable in patients with congestive heart failure and a higher range (0.8–2.0 ng/mL) is needed in patients with atrial tachyarrhythmia. The Konishi equation is widely used to predict the serum digoxin concentration (SDC) in Japan. This study assessed the correlation between SDC predicted by the Konishi equation and that actually measured in Chinese patients and investigated the impact of renal function on SDC.MethodsThe study subjects comprised 72 patients with cardiac failure or/and atrial tachyarrhythmia seen at our hospital from January 2012 to December 2013. The patients were divided into five groups according to Kidney Diseases Outcome Quality Initiative guidelines. SDCs were measured using the Abbott Architect i1000 immunology analyzer. The correlations between measured SDCs and calculated SDCs and between clearance of digoxin and creatinine clearance rate were assessed retrospectively.ResultsThe correlation between measured and predicted SDC calculated by the Konishi equation was significant (r=0.655, P<0.001) for the 72 patients overall; however, correlations within the different stages of renal function were nonsignificant, with a correlation found only in patients with stage 3 (30 mL per minute < creatinine clearance <60 mL per minute). With regard to the correlation between clearance of digoxin and creatinine clearance, our results show that although there was a significant correlation between clearance of digoxin and creatinine clearance in the group overall, correlations were not evident within the different stages of renal function.ConclusionThe results of this study indicate that clearance of digoxin and the creatinine clearance rate cannot be explained by renal function alone and that the validity of the Konishi equation for individualizing the digoxin dosage in Chinese patients is limited, being applicable only in stage 3 renal disease. Further research in larger numbers of patients across all stages of renal function will be required in the future to verify the original Konishi model.

A perspective on re‐evaluating digoxin's role in the current management of patients with chronic systolic heart failure: targeting serum concentration to reduce hospitalization and improve safety profile

Digoxin improves exercise tolerance and reduces hospitalizations in patients with systolic heart failure, but its use has declined progressively for the past two decades. The Digitalis Investigation Group trial showed that digoxin reduced hospitalizations but had a neutral effect on total mortality. There was evidence that mortality caused by worsening heart failure was less, but there was also a signal suggesting an increase in other cardiac (presumed arrhythmic) death. Use of digoxin has declined substantially and recent guideline recommendations have significantly de-emphasized the importance of this drug in the management of heart failure. Two developments suggest that re-evaluation of the contemporary role of digoxin in the management of heart failure with reduced ejection fraction is warranted. First, heart failure remains progressive, characterized by chronic debility, exercise intolerance, and frequent and costly hospitalizations, despite evidence-based drug and device therapies that prolong survival. Health economics have made reducing hospitalizations in patients with heart failure a major priority. Second, a strong association has emerged between serum concentration and the safety and efficacy of digoxin, which indicates a change in our approach to dosing this agent is needed. Experimental and clinical results suggest that optimizing therapeutic benefit and avoiding harm means dosing to achieve low serum digoxin concentrations (0.5-0.9 ng/mL). Digoxin is an inexpensive agent and the totality of evidence indicates that it reduces hospitalizations and improves symptoms safely when dosed to achieve low serum concentrations. These findings suggest digoxin should have a more prominent therapeutic role in patients with heart failure and reduced ejection fraction.

Bidirectional tachycardia after an acute intravenous administration of digitalis for a suicidal gesture.

Acute digoxin intoxication is a life-threating condition associated with severe cardiotoxicity. Female gender, age, low lean body mass, hypertension, and renal insufficiency may worsen the prognosis. Arrhythmias caused by digitalis glycosides are characterized by an increased automaticity coupled with concomitant conduction delay. Bidirectional tachycardia is pathognomonic of digoxin intoxication, but it is rarely observed. An 83-year-old woman was admitted to the Emergency Department after self-administration of 5 mg of digoxin i.v. for suicidal purpose. Her digoxin serum concentration was 17.4 ng/mL. The patient developed a bidirectional tachycardia and the Poison Control Center of the hospital provided digoxin immune fab. Bidirectional tachycardia quickly reversed and the patient remained stable throughout the hospital stay. This case shows that a multiple disciplinary approach, involving cardiologists and toxicologists, is essential for the management of digoxin intoxication. The optimal treatment of this rare event depends on the clinical conditions and on the serum drug concentration of the patient. Digoxin immune fab represents a safe, effective, and specific method for rapidly reversing digitalis cardiotoxicity and should be started as soon as the diagnosis is defined.

Sudden Blindness in a Hemodialysis Patient on Digoxin

A hemodialysis patient with atrial fibrillation and ischemic heart disease, already taking amiodarone and diltiazem, presented with complete blindness after commencing digoxin. A highly elevated serum digoxin concentration was discovered and treated with Digibind ® , with gradual but complete return of his vision. This case highlights a rare complication of digoxin potentiated by renal failure, medication interactions and poor communication. World J Nephrol Urol. 2014;3(2):100-102 doi: http://dx.doi.org/10.14740/wjnu155w

Management of digoxin therapy using pharmacokinetics in a patient undergoing continuous venovenous hemofiltration

The management of digoxin therapy using pharmacokinetics in a patient undergoing continuous venovenous hemofiltration (CVVH) is reported. A 46-year-old African-American woman with New York Heart Association class IV, American College of Cardiology- American Heart Association stage D heart failure arrived from an outside facility with complaints of dyspnea after minimal exertion, orthopnea, and lower-extremity edema. A transthoracic echocardiogram revealed an estimated left ventricular ejection fraction of 15%. The patient subsequently required left ventricular assist device placement on hospital day 5 as a potential bridge to transplantation. A total digoxin loading dose of 500 μg i.v. (8.2 μg/kg) was given in two divided doses six hours apart. The next morning, the serum digoxin concentration was 1.9 ng/mL, and the patient was started on a maintenance digoxin dosage of 125 μg i.v. daily. On postoperative day (POD) 20, the patient developed acute kidney injury, and CVVH was initiated. The sieving coefficient (Sc), transmembrane clearance (CLtm), digoxin concentration in ultrafiltration fluid (Cuf), and need for supplemental digoxin were determined to account for CVVH- associated digoxin loss. After 14 days of CVVH, the patient's clinical condition improved, and CVVH was transitioned to intermittent hemodialysis. On POD 66, the patient was discharged to an extended-care facility without adverse reactions related to digoxin therapy. Analysis of serum digoxin concentration and digoxin Cuf values suggested that digoxin was cleared by CVVH, allowed calculation of Sc and CLtm values, and facilitated determination of digoxin requirements in a critically ill patient requiring CVVH.

Population Pharmacokinetics Analysis and Proposed Dosing Regimen for Optimizing Serum Digoxin Concentration in Adult Patients

Population Pharmacokinetics Analysis and Proposed Dosing Regimen for Optimizing Serum Digoxin Concentration in Adult Patients

Evaluation of chromosome aberrations induced by digoxin in Chinese hamster ovary cells.

Digoxin is a cardiac glycoside that has been reported to inhibit growth of multiple tumor cell types in vitro. The present study was assessing the cytogenetic effects of this drug on Chinese Hamster Ovary (CHO) cells. All experiments were performed in triplicate. The IC50 was 22.5 ± 0.8 µg/ml. To investigate the clastogenic effects of drug, chromosomal aberration in metaphase cells were analyzed. Chromatid breaks and polyploidy were the main types of aberration. Mitomycin-C and sodium arsenite were used as positive controls. CHO cells were exposed to different concentration of drug (5, 10, 15, 20 µg/ml) in 24 hours. All of the study aberrations and frequency of aberrant cells significantly increased as a function of digoxin concentration (for chromatid breaks: r = 0.881, df = 13, P < 0.001; for polyploidy: r = 0.777, df = 13, P = 0.001; for cells with aberrations: r = 0.926, df = 13, P < 0.001). The mitotic index negatively correlated with the concentration of digoxin (r = -0.978, df = 13, P < 0.001). All concentrations that cause chromosomal aberrations are in the cytotoxic range of the drug. The peak serum digoxin concentration (5 - 20 ng/ml) was very lower than concentrations we used in the present experiments. Further studies on valuation of chromatid breaks, micronuclei, and sister chromatid exchange in lymphocytes of patients who received digoxin, were recommended.

Evaluation of digoxin concentration after loading dose in patients with renal dysfunction.

Loading dose recommendations for digoxin are based on the volume of distribution, which is proportional to lean body weight, whereas maintenance dose recommendations depend on renal function. The volume of distribution of this drug is demonstrably reduced in severe renal dysfunction, but the threshold at which a reduction in loading dose is warranted remains unknown. To describe the practice of digoxin loading at The Ottawa Hospital and to determine the proportion of patients, categorized by degree of renal function, who experienced digoxin toxicity after a loading dose. Data were collected retrospectively from charts of patients who had received a digoxin loading dose between May 2008 and January 2012, with a blood sample drawn for determination of digoxin concentration 6 to 24 h later. Patients were categorized into 4 groups according to creatinine clearance. The mean loading dose of digoxin (± standard deviation) was 9.8 ± 4.1 μg/kg among patients with creatinine clearance below 15 mL/min, 14.4 ± 5.4 μg/kg for those with creatinine clearance between 15 and 29 mL/min, 16.0 ± 5.6 μg/kg for those with creatinine clearance between 30 and 59 mL/min, and 14.0 ± 3.7 μg/kg for those with creatinine clearance 60 mL/min or above. Degree of renal dysfunction, particularly creatinine clearance below 60 mL/min, predicted the likelihood of experiencing a toxic serum concentration of digoxin after the loading dose, after adjustment for dose and weight (odds ratio 2.60, 95% confidence interval 1.55-4.39). Patients with creatinine clearance below 60 mL/min were more likely than those with creatinine clearance of 60 mL/min or greater to experience toxic serum digoxin concentrations with current loading dose strategies. It is recommended that loading doses be reduced (to 6-10 μg/kg) for these patients. Prospective trials are required to determine the clinical implications of these findings and to determine if greater reductions in loading dose are required for patients with severe renal dysfunction (i.e., creatinine clearance below 30 mL/min).

Oleander toxicosis in equids: 30 cases (1995–2010)

To determine clinical, laboratory analysis, and necropsy findings for equids with oleander toxicosis and to identify factors associated with outcome. Retrospective case series. 30 equids. Medical records of equids with detectable concentrations of oleandrin in serum, plasma, urine, or gastrointestinal fluid samples and equids that had not received cardiac glycoside drugs but had detectable concentrations of digoxin in serum were identified via a medical records database search. Descriptive statistics were calculated for medical history, physical examination, laboratory analysis, and necropsy variables. Logistic regression analysis was used to identify physical examination and laboratory analysis factors significantly associated with outcome. 3 of 30 (10.0%) equids died before or immediately after arrival at the hospital. Of the other 27 equids, 23 (85.2%) had gastrointestinal tract abnormalities, azotemia was detected for 19 (70.4%), and a cardiac arrhythmia was ausculted for 18 (66.7%). Mortality rate for all equids was 50.0%; mortality rate for hospitalized equids was 44.4%. The most common cause of death was cardiac dysfunction. Odds of survival to discharge from the hospital were lower for equids with cardiac arrhythmias versus those without arrhythmias and decreased with increasing Hct and serum glucose concentrations. Odds of survival increased with increasing serum chloride concentration and duration of hospitalization. Equids with oleander toxicosis frequently had simultaneous gastrointestinal tract, cardiac, and renal problems. Oleander intoxication should be a differential diagnosis for equids with colic in geographic areas where oleander is found, especially when azotemia or cardiac arrhythmias are detected concurrently.

Digoxin for patients with atrial fibrillation and heart failure: paradise lost or not?

This editorial refers to ‘Increased mortality among patients taking digoxin—analysis from the AFFIRM study’, by M.G. Whitbeck et al. , doi:10.1093/eurheartj/ehs348 Digoxin is one of the oldest drugs in cardiovascular medicine, and it was traditionally used in patients with atrial fibrillation (AF) and heart failure (HF).1 In the last 20 years, the use of this drug has markedly declined, and in the most recent 2012 European Society of Cardiology (ESC) HF Guidelines,2 it is stated that for patients with HF and a left ventricular ejection fraction (LVEF) ≤40%, who are in sinus rhythm ‘digoxin may be used’. This recommendation is based on the Digitalis Investigation Group (DIG) trial,3 in which the effect of digoxin on outcome was examined in 6800 patients with HF. For HF patients with AF, other drugs (in particular beta-blockers) should be preferred,2 since they provide better rate control. In the 2010 ESC AF Guidelines,4 it is stated that digoxin is effective for long-term rate control at rest, but not during exercise. Prospective, randomized, placebo-controlled outcome studies examining the effect of digoxin in patients with AF (with or without HF) are not available. In the past, it was assumed that the beneficial effect of digoxin in HF was due to its (positive) inotropic properties, which were more pronounced at higher doses of the drug.1,5 However, a large number of studies in patients with HF has shown that positive inotropic drugs lead to an unfavourable effect on outcome, and these drugs are now contraindicated in patients with (chronic) HF. In contrast to this inotropic effect, digoxin also exerts potentially favourable autonomic- or neurohormonal-inhibiting properties,6,7 which primarily occur at lower serum digoxin concentrations (SDCs).1,5–7 This has been increasingly recognized in the last 25 years, …

Correlation between Serum Digoxin Concentration and Impaired Renal or/and Hepatic Functions in Cardiac Patients

Correlation between Serum Digoxin Concentration and Impaired Renal or/and Hepatic Functions in Cardiac Patients

&lt;span class="caption"&gt;TECHNICAL REPORT:&lt;/span&gt; Investigation of Possible Interference by Digoxin-Like Immunoreactive Substances on the Architect� &lt;i&gt;i&lt;/i&gt;Digoxin CMIA in Serum Samples from Pregnant Women, and Patients with Liver Disease, Renal Insufficiency, Critical Illness, and Kidney and Liver Transplant

Although the possible interference of digoxin-like immunoreactive substances (DLIS) on the Architect iDigoxin chemiluminiscent microparticle immunoassay (CMIA) has been emphasized by the manufacturer, a specific study about this subject has still not been carried out. Apparent serum digoxin concentrations were determined using the Architect iDigoxin CMIA from Abbott Laboratories in digoxin-free pregnant women (n = 50), and patients with liver disease (n = 50), renal insufficiency (n = 50), kidney (n = 25) or liver (n = 25) transplant, and critical illness (n = 50). In all of the patients included in this study, apparent serum digoxin concentrations were lower than the correspondent quantification limit (< 0.30 microg/L). The Architect iDigoxin CMIA assay would be relatively free from endogenous DLIS positive interferences.

2012 American College of Clinical Pharmacology Annual Meeting September 23rd–25th San Diego, California

2012 American College of Clinical Pharmacology Annual Meeting September 23^rd–25^th San Diego, California

Clinically Insignificant Negative Interferences of Spironolactone, Potassium Canrenoate, and Their Common Metabolite Canrenone in New Dimension Vista LOCI Digoxin Immunoassay

Spironolactone, a potassium-sparing diuretic metabolized to canrenone is often used with digoxin to treat various conditions including congestive heart failure. Potassium canrenoate is a similar drug, which is also metabolized to canrenone. Due to reported both positive and negative interference of spironolactone, potassium canrenoate, and their common metabolite canrenone with digoxin immunoassays, we investigated potential interference of these compounds with the new homogenous sequential chemiluminescent assay for digoxin based on the luminescent oxygen channeling technology (LOCI digoxin) for application on the Dimension and Vista platform. When aliquots of a drug-free serum pool were supplemented with various amounts of spironolactone, potassium canrenoate, or canrenone and apparent digoxin values were measured using Dimension Vista LOCI digoxin assay, we observed no detected value except when aliquots were supplemented with very high amounts of potassium canrenoate or canrenone. However, we observed that apparent digoxin concentrations were very low. When aliquots of a serum digoxin pool (prepared by pooling specimens from patients receiving digoxin), were further supplemented with various amounts of spironolactone, potassium canrenoate, or canrenone and serum digoxin concentrations were remeasured using the LOCIdigoxin assay, only statistically significant falsely lower digoxin values (negative interference) were observed in specimens containing very high amounts of canrenone or potassium canrenoate. However, such small bias may not have any clinical significance. We conclude that new Dimension Vista LOCI digoxin assay is virtually free from interferences of spironolactone, potassium canrenoate, and their common metabolite canrenone.

Digitalis Intoxication Induced by an Acute Accidental Poisoning by Lily of the Valley

An 87-year-old woman suffering from advanced dementia was admitted on May 1, 2010, for an accidental ingestion of 2 sprigs of lily of the valley offered to her by her family. She arrived 2 hours after ingestion to the emergency department with digestive disorders (nausea and an episode of vomiting). An initial clinical examination found a blood pressure of 155/85 mm Hg, a heart rate of 45 bpm, and a normal cardiovascular examination. The initial ECG showed sinus bradycardia at 45 bpm and repolarization disorders in the anterior and lateral derivations (Figure 1A). Her kalemia was 4.4 mmol/L, plasma creatinine was 66 μmol/L, and troponin was <0.06 μg/L. Her digoxin serum concentration was in the therapeutic range. The patient was hospitalized in the intensive care unit with continuous ECG and hemodynamic monitoring. Three hours later, her heart rate and blood pressure were normalized at 70 …

The effect of age and everyday exercise on steady-state plasma digoxin concentrations.

Age-related physiologic changes may significantly alter the disposition and pharmacologic characteristics of many drugs. The elderly are the most frequent users of digoxin because of increased prevalence of atrial fibrillation and congestive heart failure. This study was conducted to confirm the decrease in digoxin concentrations during exercise, to determine if age is a factor in this decrease, and to explore the difference between chronologic age and physiologic age. Eighteen men age 50-85 years were treated with digoxin for more than 1 month before enrolling and had serum digoxin concentrations of 0.4-2.0 micrograms/L. They were evaluated during a 3-hour period in the morning (A.M. dose withheld). Blood samples were obtained every 10 minutes during sequential 60-minute periods of rest (phase I), walking (phase II), and rest (phase III). There were no significant differences in mean concentration between phases II and I (p < 0.76), phases III and phase I (p < 0.70), or phases II and III (p < 0.37). The effect of age was positively correlated with the mean concentration of phase II but was not statistically significant (p < 0.62). Statistically significant correlations were seen only between the exercise phase and serum albumin and Mini-Mental Status Examination scores. We conclude that exercise has minimal, if any, clinically relevant effects on plasma digoxin concentrations. Increasing chronologic age has no influence on a decrease in the concentrations with exercise; a younger physiologic age may play a role.

Clinical Utility of Serum Digoxin Level in Cardiac Patients for Diagnosis of Chronic Digitalis Toxicity

Digitalis toxicity is a complication of the digitalis therapy. It could occur also due to the patient taking in a much larger dose of the drug than prescribed. The general symptoms of Digitalis toxicity are typically gastro-intestinal, neurologic and non-specific cardiac type manifestations that are strikingly similar to the clinical picture of primary Congestive Heart Failure (CHF) making a diagnosis of chronic digitalis toxicity in particular relatively difficult. Serum digoxin measurement is today becoming a crucial subject of concern because of the narrow therapeutic window of digoxin besides increasing mortality and morbidity due to its intoxication. The present work is focused on evaluating the clinical value of Serum Digoxin Concentrations (SDCs) in relation to appropriate assessment of chronic digitalis toxicity in cardiac patients. The current study was conducted in the form of a cross-sectional Electronic Medical Record (EMR) review study of patients presently on continuous prescriptions for digoxin with there being zero gaps in therapy for at least 10 days prior to SDC result entered into the Online Analytical Toxicology Request Result (OTARR). There was also a complete clinical examination report as well as a review of the results of serum potassium concentration, liver and kidney functions. Patients with digoxin toxicity (11.9%) had a significantly higher mean SDC (2.75 ± 1.2) than those with subtherapeutic (0.67 ± 0.17 ng/mL) or eutherapeutic SDC (1.19 ± 0.26 ng/mL) (p value ≤ 0.05). About 12% of the total cases showed an abnormal serum potassium concentration of electrolyte fluctuations. From this, one can conclude that a regular monitoring of serum digoxin level would be seen as mandatory for the verification of digoxin’s therapeutic effects and then the subsequent prevention and early diagnosis of chronic toxicity.

Abstract 17353: Effectiveness and Safety of Digoxin in Adults with Incident Systolic Heart Failure

Background: Current clinical guidelines endorse digoxin use for patients with symptomatic systolic heart failure (HF) on optimal medical therapy, but this recommendation is based on limited, older clinical trial data. We sought to evaluate the effectiveness and safety of digoxin in a contemporary cohort of patients with incident systolic heart failure and stratified by patient sex and serum digoxin concentration (SDC). Methods: We identified patients with incident systolic HF between 2006 and 2008 in the Kaiser Permanente of Northern California health system. We used multivariable extended Cox regression to examine the association between incident digoxin use and death and hospitalization for HF, controlling for patient medical history, physical exam, diagnostic tests, laboratories, and medications. Longitudinal drug use, patient characteristics and outcomes were identified based on validated algorithms using health plan automated databases. Analyses were also conducted stratifying by sex and SDC. Results: Among 2891 patients with incident systolic HF followed for a mean 2.4 years, digoxin users had higher rates of death (14.2% vs 11.3%) and HF hospitalization (28.2% vs 24.4%). In adjusted analysis, digoxin was associated with excess mortality (odds ratio (OR) 1.60, 95% confidence interval (CI) 1.18-2.17) and HF hospitalization (OR 1.40, 95% CI 1.05-1.86). Compared with non-use, new digoxin use with SDC ≥1.2 ng/mL had higher odds of HF hospitalization and borderline higher odds of death (Table); SDC ≤0.8 ng/mL had higher odds of death. Digoxin use was associated with higher adjusted rates of HF hospitalization and death in men but not in women (Table). Conclusions: Digoxin was associated with a higher risk of death and HF hospitalization, however these risks were dependent on SDC. Digoxin was linked to a higher risk of adverse events in men but not significantly so for women.