Contemporary Trends in the Use of and Expenditures on Digoxin in the United States.

BACKGROUND: Digoxin is indicated for the management of heart failure with reduced ejection fraction and atrial fibrillation. Despite stronger guideline recommendations for other pharmacologic and device therapies, digoxin retains a role in select patients unable to tolerate or refractory to standard therapies. Contemporary utilization of and costs related to digoxin in the United States of America (USA) remain uncharacterized. The objective of this study was to estimate trends in digoxin use and expenditures across the USA from 2010 to 2017. METHODS: We utilized the Medical Expenditure Panel Survey to estimate trends in digoxin use and expenditures across the USA from 2010 to 2017. The Medical Expenditure Panel Survey is an overlapping panel survey that interviews households in the USA to ascertain their healthcare utilization and expenditures. Complex sampling procedures allow for nationally representative estimates of utilization and expenditures. We report the number of digoxin users and expenditures across key subgroups in 2-year increments from 2010 to 2017. RESULTS: The number of digoxin users in the USA declined by 47% from 766 users per 100,000 adults in 2010-11 to 402 users per 100,000 adults in 2016-17. While digoxin use declined among women and self-identified White adults, adults living at or below the federal poverty level and those who self-identified as Asian or Hispanic represent an increasing proportion of overall digoxin users. While nationwide digoxin expenditures declined by 26% from 2010-11 to 2012-13, they peaked at $260.3 million in 2014-15 and remained elevated at $188.7 million in 2016-17. CONCLUSIONS: Despite a nationwide trend towards declining use, digoxin remains prevalent amongst people of Asian and Hispanic descent in the USA. After a spike in cost in 2013, digoxin prices have yet to return to pre-spike levels. The role of digoxin in contemporary heart failure and arrhythmia management will continue to evolve as additional randomized and observational analyses become available.

Frequency of Clinical Monitoring of Serum Concentrations of Digoxin, Potassium, and Creatinine, and Recording of Electrocardiograms in Digoxin-Treated Patients: A Japanese Claims Database Analysis.

Guidelines for cardiovascular drug therapy recommend monitoring serum digoxin concentration (SDC) in patients receiving digoxin treatment, especially those with renal dysfunction and hypokalemia. However, only a few studies have reported the prevalence of SDC monitoring and laboratory testing in clinical practice. Therefore, the aim of this study was to describe the frequency of SDC monitoring and laboratory testing in digoxin users and to assess the association between SDC monitoring and patient characteristics. We used the Japanese insurance claims data covering approximately 1.7 million patients aged 20-74 years between January 1, 2005 and March 31, 2014. All patients who had at least one prescription for digoxin were included. The frequency of SDC and laboratory tests was calculated and the association between patient characteristics and SDC monitoring was assessed using logistic regression analysis. A total of 98867 prescriptions of digoxin were issued to 3458 patients between 2005 and 2014. The annual mean frequencies of monitoring SDC, serum potassium level and serum creatinine level and of recording electrocardiograms was 16.8, 34.8, 38.7, and 24.1%, respectively. Atrial fibrillation, chronic heart failure, renal diseases, and use of oral anticoagulants were associated with SDC monitoring. We found the frequency of SDC monitoring to be relatively low in Japanese clinical practice.

Digoxin Use and Outcomes in Patients With Heart Failure With Reduced Ejection Fraction.

BACKGROUND: Heart failure is a leading cause for hospital readmission. Digoxin use may lower this risk in patients with heart failure with reduced ejection fraction (HFrEF), but data on contemporary patients receiving other evidence-based therapies are lacking. METHODS: Of the 11,900 patients with HFrEF (ejection fraction ≤45%) in Medicare-linked OPTIMIZE-HF, 8401 were not on digoxin, of whom 1571 received discharge prescriptions for digoxin. We matched 1531 of these patients with 1531 not receiving digoxin by propensity scores for digoxin use. The matched cohort (n = 3062; mean age, 76 years; 44% women; 14% African American) was balanced on 52 baseline characteristics. We assembled a second matched cohort of 2850 patients after excluding those with estimated glomerular filtration rate <15 mL/min/1.73 m2 and heart rate <60 beats/min. Hazard ratios (HRs) and 95% confidence intervals (CIs) for digoxin-associated outcomes were estimated in the matched cohorts. RESULTS: Among the 3062 matched patients, digoxin use was associated with a significantly lower risk of heart failure readmission at 30 days (HR, 0.74; 95% CI, 0.59-0.93), 1 year (HR, 0.81; 95% CI, 0.72-0.92), and 6 years (HR, 0.90; 95% CI 0.81-0.99). The association with all-cause readmission was significant at 1 and 6 years but not 30 days. There was no association with mortality. Similar associations were observed among the 2850 matched patients without bradycardia or renal insufficiency. CONCLUSIONS: Among hospitalized older patients with HFrEF receiving contemporary treatments for heart failure, digoxin use is associated with a lower risk of hospital readmission but not all-cause mortality.

Pharmacoclinical audit on the use of digitalis in patients aged over 75 years hospitalized in an acute geriatric unit.

Digitalis remains a treatment that is difficult to manage, especially in the elderly. METHODS: A retrospective, unicentric study carried out within the unit of Internal medicine and geriatrics, Reims University Hospital Center, between January and June 2014. Collection of all patients hospitalized, after 75 years, receiving treatment with digitalis, either as soon as they enter (present on the usual prescription of the patient), during their hospitalization and on their exit. RESULTS: 20 patients were included. The median age was 89 years (range: 78-94). Digitalis was only used in slowing down the ventricular rate during atrial fibrillation; 7 patients (35%) had a high serum digoxin concentration, of which 4 had renal failure. Three patients presented a digital cup on the electrocardiogram. In our series, in digoxin overdosage, 3 patients with electrical signs of digoxin overdosage have all 3 digoxin-beta-blockers. We are in the limit of the significance, for the connection between digoxinemia and the appearance of electrical signs of overdose in digitalis (p=0.06). CONCLUSION: Digoxin therefore remains a drug that is difficult to manage, mainly in the elderly, as there are many clinical, biological drug and therapeutic constraints. Failure to comply with the rules for the use and monitoring of digoxin may prove fatal in the elderly.

Cost-effectiveness of digoxin, pacing, and direct current cardioversion for conversion of atrial flutter in neonates.

IntroductionNewborn atrial flutter can be treated by medications, pacing, or direct current cardioversion. The purpose is to compare the cost-effectiveness of digoxin, pacing, and direct current cardioversion for the treatment of atrial flutter in neonates.Materials and methodsA decision tree model was developed comparing the efficacy and cost of digoxin, pacing, and direct current cardioversion based on a meta-analysis of published studies of success rates of cardioversion of neonatal atrial flutter (age<2 months). Patients who failed initial attempt at cardioversion progressed to the next methodology until successful. Data were analysed to assess the cost-effectiveness of these methods with cost estimates obtained from 2015 Medicare reimbursement rates. RESULTS: The cost analysis for cardioversion of atrial flutter found the most efficient method to be direct current cardioversion at a cost of $10 304, pacing was next at $11 086, and the least cost-effective was digoxin at $14 374. The majority of additional cost, regardless of method, was from additional neonatal ICU day either owing to digoxin loading or failure to covert. Direct current cardioversion remains the most cost-effective strategy by sensitivity analyses performed on pacing conversion rate and the cost of the neonatal ICU/day. Direct current cardioversion remains cost-effective until the assumed conversion rate is below 64.6%. CONCLUSION: The most cost-efficient method of cardioverting a neonate with atrial flutter is direct current cardioversion. It has the highest success rates based on the meta-analysis, shorter length of stay in the neonatal ICU owing to its success, and results in cost-savings ranging from $800 to $4000 when compared with alternative approaches.

Pharmacokinetic monitoring of chronic treatment with digoxin from Primary Health Care.

INTRODUCTION: The serum digoxin concentration (SDC) should be between 0.8 and 2 ng/ml. The objective is to assess the pharmacokinetic monitoring of SDC performed from primary healthcare (PH) in patients with chronic treatment. METHODS: Cross-sectional retrospective study of patients with chronic treatment with digoxin belonging to the department of a General University Hospital.Data were analized: age, sex, diagnosis, number of serum digoxin concentration determinations, date and origin of the request for monitoring, analytical result and pharmacokinetic assessment are collected. RESULTS: 624 patients are undergoing chronic treatment with digoxin, 68% women, mean age 78.4 (39-98) years. 308 (49.4%) patients haven't analytical determination of SDC (Group 1), 183 (29.3%) patients have a SDC occasionally performed with a request from specialist care (Group 2) and 133 (21,3%) patients have CSD performed with a request from primary healthcare doctors, with an average of 2.42 monitoring per patient and year (Group 3). These are those patients who have pharmacokinetic monitoring of chronic treatment with digoxin. Of the group 2.25 (13.6%) patientes were hospital admission from emergency department for presenting digitalis intoxication with CSD>2 ng/ml, and 39 (21.3%) patients for low dosing with CSD<0.5 ng/ml. Group 3.4 (3%) patients presented digitalis intoxication and 5 (3.8%) for insufficient dosing. CONCLUSIONS: A small proportion of patients undergoing chronic treatment with digoxin are under pharmacokinetic monitoring and a reduction in complications derived from inappropriate CSD compared to those not under pharmacokinetic follow-up is observed.

Introducción: La concentración sérica de digoxina (CSD) debe situarse entre 0,8 y 2 ng/ml. El objetivo es valuar el seguimiento farmacocinético de las CSD que se realiza desde Atención Primaria (AP) en pacientes con tratamiento crónico.Métodos: Estudio trasversal observacional retrospectivo de pacientes en tratamiento crónico con digoxina que pertenecen al departamento de un Hospital General Universitario. Se recogen datos de edad, sexo, diagnóstico, número de determinaciones séricas de digoxina realizadas, fecha y origen de la solicitud de monitorización, resultado analítico y valoración farmacocinética. (Infradosificación, normodosificación o supradosificación).Resultados: 624 pacientes están en tratamiento crónico con digoxina: 68% mujeres, edad media 78,4 (39-98) años. 308 (49,4%) pacientes no tienen realizada ninguna determinación analítica de CSD (Grupo 1), 183 (29,3%) pacientes tienen CSD realizadas de manera esporádica con solicitud tramitada desde Atención Especializada (Grupo 2) y 133 (21,3%) pacientes tienen CSD realizadas de manera periódica con solicitud cursada por médicos de AP, con un promedio de 2,42 monitorizaciones por paciente y año (Grupo 3). Estos son los que tienen un seguimiento farmacocinético del tratamiento crónico con digoxina.Del Grupo 2,2(13,6%) entran por el Servicio de Urgencias por presentar intoxicación digitálica con CSD>2 ng/ml, y 39 (21,3%) pacientes por baja dosificación con CSD<0,5ng/ml. Del Grupo 3,4 (3%) presentan intoxicación digitálica y 5 (3,8%) infradosificación.Conclusiones: Una pequeña parte de los pacientes que se encuentran en tratamiento crónico con digoxina están en seguimiento farmacocinético. Se observa una reducción de las complicaciones derivadas de CSD inapropiadas con respecto a los que no están en seguimiento farmacocinético.

Effect of Digoxin Use Among Medicaid Enrollees With Atrial Fibrillation.

BACKGROUND: Recently published analysis of contemporary atrial fibrillation (AF) cohorts showed an association between digoxin and increased mortality and hospitalizations; however, other studies have demonstrated conflicting results. Many AF cohort studies did not or were unable to examine racial differences. Our goal was to examine risk factors for hospitalizations and mortality with digoxin use in a diverse real-world AF patient population and evaluate racial differences. METHODS AND RESULTS: We performed a retrospective cohort analysis of claims data for Medicaid beneficiaries, aged 18 to 64 years, with incident diagnosis of AF in 2008 with follow-up until December 31, 2009. We created Kaplan-Meier curves and constructed multivariable Cox proportional hazard models for mortality and hospitalization. We identified 11 297 patients with an incident diagnosis of AF in 2008, of those, 1401 (12.4%) were on digoxin. Kaplan-Meier analysis demonstrated an increased risk of hospitalization with digoxin use overall and within race and heart failure groups. In adjusted models, digoxin was associated with an increased risk of hospitalization (adjusted hazard ratio, 1.54; 95% confidence interval, 1.39-1.70) and mortality (adjusted hazard ratio, 1.50; 95% confidence interval, 1.05-2.13). Overall, blacks had a higher risk of hospitalization but similar mortality when compared with whites regardless of digoxin use. We found no significant interaction between race and digoxin use for mortality (P=0.4437) and hospitalization (P=0.7122). CONCLUSIONS: Our study demonstrates an overall increased risk of hospitalizations and mortality with digoxin use but no racial/ethnic differences in outcomes were observed. Further studies including minority populations are needed to critically evaluate these associations.

Few Disparities in Baseline Laboratory Testing After the Diuretic or Digoxin Initiation by Medicare Fee-For-Service Beneficiaries.

BACKGROUND: Despite the persistence of significant disparities, few evaluations examine disparities in laboratory testing by race/ethnicity, age, sex, Medicaid eligibility, and number of chronic conditions for Medicare fee-for-service beneficiaries' newly prescribed medications. In Medicare beneficiaries initiating diuretics or digoxin, this study examined disparities in guideline-appropriate baseline laboratory testing and abnormal laboratory values. METHODS AND RESULTS: To evaluate guideline-concordant testing for serum creatinine and serum potassium within 180 days before or 14 days after the index prescription fill date, we constructed retrospective cohorts from 10 states of 99 711 beneficiaries who had heart failure or hypertension initiating diuretic in 2011 and 8683 beneficiaries who had heart failure or atrial fibrillation initiating digoxin. Beneficiaries initiating diuretics were less likely to have testing if they were non-Hispanic Black (relative risk [RR], 0.99; 95% confidence interval [CI], 0.98-0.99) than non-Hispanic White. Beneficiaries initiating diuretics and beneficiaries initiating digoxin were more likely to have testing if they had multiple chronic conditions relative to 0 to 1 conditions. Beneficiaries initiating diuretics with laboratory values were more likely to have an abnormal serum creatinine value at baseline if they were non-Hispanic Black (RR, 2.57; 95% CI, 1.91-3.44), other race (RR, 2.11; 95% CI, 1.08-4.10), or male (RR, 2.75; 95% CI, 2.14-3.52) or an abnormal serum potassium value if they were aged ≥76 years (RR, 1.29; 95% CI, 1.09-1.51) or male (RR, 1.17; 95% CI, 1.03-1.33). CONCLUSIONS: Testing rates were consistently high, so there were negligible disparities in guideline-concordant testing of creatinine and potassium after the initiation of digoxin or diuretics by Medicare beneficiaries.

Digoxin Toxicity and Use of Digoxin Immune Fab: Insights From a National Hospital Database.

OBJECTIVES: This study was developed to determine contemporary management of digoxin toxicity and clinical outcomes. BACKGROUND: Although the use of digoxin in heart failure management has declined, toxicity remains a prevalent complication. METHODS: The Premier Perspective Comparative Hospital Database (Premier Inc., Charlotte, North Carolina) was used to retrospectively identify patients diagnosed with digoxin toxicity and/or who received digoxin immune fab (DIF) over a 5-year period (2007 to 2011). DIF was evaluated using treatment date, number of vials administered, and total cost. Clinical outcomes included length of stay (total hospitalization; days after DIF), cost of hospitalization, and in-hospital mortality. Exploratory multivariate analyses were conducted to determine predictors of DIF and effect on length of stay, adjusting for patient characteristics and selection bias. RESULTS: Digoxin toxicity diagnosis without DIF treatment accounted for 19,543 cases; 5,004 patients received DIF of whom 3086 had a diagnosis of toxicity. Most patients were >65 years old (88%). The predictors of DIF use were urgent/emergent admission, hyperkalemia, arrhythmia associated with digoxin toxicity, acute renal failure, or suicidal intent (odds ratios 1.7, 2.4, 3.6, 2.1, and 3.7, respectively; p < 0.0001 for all). The majority (78%) of DIF was administered on days 1 and 2 of the hospitalization; 10% received treatment after day 7. Digoxin was used after DIF administration in 14% of cases. Among patients who received DIF within 2 days of admission, there was no difference for in-hospital mortality or length of stay compared with patients not receiving DIF. CONCLUSIONS: Digoxin toxicity diagnoses are clustered in the elderly. One-fifth of cases receive treatment with DIF, most within 2 days of admission. Opportunities exist for improved diagnosis and post-DIF management. Prospective data may be required to assess the impact of DIF on length of stay.

Heart failure in African Americans: disparities can be overcome.

African Americans are disproportionately affected by heart failure, with a high prevalence at an early age. Hypertension, diabetes, obesity, and chronic kidney disease are all common in African Americans and all predispose to heart failure. Neurohormonal imbalances, endothelial dysfunction, genetic polymorphisms, and socioeconomic factors also contribute. In general, the same evidence-based treatment guidelines that apply to white patients with heart failure also apply to African Americans. However, the combination of hydralazine and isosorbide dinitrate is advised specifically for African Americans.

Effectiveness and safety of digoxin among contemporary adults with incident systolic heart failure.

BACKGROUND: Clinical guidelines recommend digoxin for patients with symptomatic systolic heart failure (HF) receiving optimal medical therapy, but this recommendation is based on limited, older trial data. We evaluated the effectiveness and safety of digoxin in a contemporary cohort of patients with incident systolic HF. METHODS AND RESULTS: We identified adults with incident systolic HF between 2006 and 2008 within Kaiser Permanente Northern California who had no prior digoxin use. We used multivariable extended Cox regression to examine the association between new digoxin use and risks of death and HF hospitalization, controlling for medical history, laboratory results, medications, HF disease severity, and the propensity for digoxin use. We also conducted analyses stratified by sex and concurrent ß-blocker use. Among 2891 newly diagnosed patients with systolic HF, 529 (18%) received digoxin. During a median 2.5 years of follow-up, incident digoxin use was associated with higher rates of death (14.2 versus 11.3 per 100 person-years) and HF hospitalization (28.2 versus 24.4 per 100 person-years). In multivariable analysis, incident digoxin use was associated with higher mortality (hazard ratio, 1.72; 95% confidence interval, 1.25-2.36) but no significant difference in the risk of HF hospitalization (hazard ratio, 1.05; 95% confidence interval, 0.82-1.34). Results were similar in analyses stratified by sex and ß-blocker use. CONCLUSIONS: Digoxin use in patients with incident systolic HF was independently associated with a higher risk of death but no difference in HF hospitalization.

Digoxin reduces 30-day all-cause hospital admission in older patients with chronic systolic heart failure.

BACKGROUND: Heart failure is a leading cause of hospital admission and readmission in older adults. The new United States healthcare reform law has created provisions for financial penalties for hospitals with higher than expected 30-day all-cause readmission rates for hospitalized Medicare beneficiaries aged ≥65 years with heart failure. We examined the effect of digoxin on 30-day all-cause hospital admission in older patients with heart failure and reduced ejection fraction. METHODS: In the main Digitalis Investigation Group trial, 6800 ambulatory patients with chronic heart failure (ejection fraction ≤45%) were randomly assigned to digoxin or placebo. Of these, 3405 were aged ≥65 years (mean age, 72 years; 25% were women; 11% were nonwhite). The main outcome in the current analysis was 30-day all-cause hospital admission. RESULTS: In the first 30 days after randomization, all-cause hospitalization occurred in 5.4% (92/1693) and 8.1% (139/1712) of patients in the digoxin and placebo groups, respectively, (hazard ratio {HR} when digoxin was compared with placebo, 0.66; 95% confidence interval {CI}, 0.51-0.86; P=.002). Digoxin also reduced both 30-day cardiovascular (3.5% vs 6.5%; HR, 0.53; 95% CI, 0.38-0.72; P<.001) and heart failure (1.7 vs 4.2%; HR, 0.40; 95% CI, 0.26-0.62; P<.001) hospitalizations, with similar trends for 30-day all-cause mortality (0.7% vs 1.3%; HR, 0.55; 95% CI, 0.27-1.11; P=.096). Younger patients were at lower risk of events but obtained similar benefits from digoxin. CONCLUSIONS: Digoxin reduces 30-day all-cause hospital admission in ambulatory older patients with chronic systolic heart failure. Future studies need to examine its effect on 30-day all-cause hospital readmission in hospitalized patients with acute heart failure.

Concurrent use of antiplatelets, anticoagulants, or digoxin with Chinese medications: a population-based cohort study.

PURPOSE: We examined the extent of concurrent use of antiplatelets, anticoagulants, or digoxin with Chinese medications (CMs) and identified its associated factors. METHODS: A retrospective cohort study was conducted using one million random samples from the Longitudinal Health Insurance Database 2005 in Taiwan. High-risk Western medications (HRWMs) focused on in this study were antiplatelets (aspirin, clopidogrel, dipyridamole, ticlopidine), anticoagulants (heparin, warfarin), and digoxin. Concurrent use was described as having an overlapping use period of HRWM with CMs any time in 2005. Baseline demographics, comorbidities, and health service utilizations between patients with and without concurrent HRWM-CM use were compared. Logistic regression analyses were performed to identify factors associated with incident concurrent use. RESULTS: Of the 70,698 eligible HRWM users, 13.2 % used CMs concurrently for an average duration of 26.7 ± 43 days. The incidence of concurrent HRWM-CM use, which excluded prior CM use within 6 months preceding the first CM use, was 6.3 %. Warfarin or ticlopidine users were more likely to be prescribed with CMs than were the other HRWM users. Factors associated with an increasing incidence of concurrent HRWM-CM use included female sex, age 45-54 years, middle monthly income, higher number of outpatient visits or distinct prescribed medications, and a previous diagnosis of heart diseases, stroke, or hypertension. In contrast, age ≥ 65 years and higher medical expenditure were associated with a lower incidence of concurrent use. CONCLUSIONS: In the Taiwanese population, approximately one in eight HRWM users were concomitantly prescribed CMs. Whether such concurrent use is associated with adverse clinical outcomes warrants further investigations.

Assessment of the appropriateness of serum digoxin concentration measurement in a medical group setting.

BACKGROUND: Recent quality initiatives require that the routine annual therapeutic drug-monitoring (TDM) parameters for the high-risk medication digoxin include a measure of renal function and a serum potassium level but not a serum digoxin concentration (SDC) measurement. Several studies have shown that the majority of the SDCs obtained in hospital settings provide little clinically actionable information. OBJECTIVE: To evaluate the appropriateness and utility of SDCs ordered in a medical group practice setting by categorizing the reason the SDC was ordered and identifying action taken in response to the result. METHODS: The descriptive study was conducted as a retrospective, electronic medical record (EMR) review of 90 primary care patients with continuous prescriptions for digoxin current on their medication profile with no gaps in therapy for at least 2 years prior to an SDC result entered into the EMR between January 1, 2009, and September 30, 2009. The reason the SDC was ordered was abstracted independently by 2 reviewers, who then assigned it to 1 of 8 predefined indication categories based on previously published criteria and practice guidelines. A third reviewer resolved inter-reviewer discrepancy (n = 1). RESULTS: A total of 90 patients with at least 1 SDC met inclusion criteria. Routine monitoring was the most frequent SDC order indication category with 35 patients (38.9%), 17 (48.6%) of whom did not have the recommended monitoring measures of potassium or renal function drawn concurrently. Patients were included in other categories as follows: confirmation of signs/symptoms of toxicity 30 (33.3%); assessment of factors altering pharmacokinetics 5 (5.6%); assessment of dosage change 5 (5.6%); assessment of drug interaction 3 (3.3%); assessment of clinical response 3 (3.3%); assessment of adherence 1 (1.1%); and other 2 (2.2%). Across all categories, a total of 19 (21.1%) of SDC results were outside the therapeutic range of 0.5 nanograms (ng) per mL and 2.0 ng per mL, 18 of which were below 0.5 ng per mL, with none of the subtherapeutic levels leading to a change in digoxin therapy. Only 1 patient (1.1%) had therapy changed in response to an elevated abnormal SDC result of 2.1 ng per mL and was in the routine monitoring category. CONCLUSIONS: The majority of SDC results obtained in our medical group setting did not lead to clinical action, such as dose adjustment or drug discontinuation. SDCs were commonly measured as part of routine monitoring, which is considered an inappropriate indication, and often without being accompanied by better markers for digoxin toxicity such as serum potassium levels and measures of renal function as recommended by drug-monitoring quality initiatives. Provider education is needed regarding the most indicative digoxin TDM parameters to obtain in order to satisfy quality initiatives.

Is there an association between external cardioversions and long-term mortality and morbidity? Insights from the Atrial Fibrillation Follow-up Investigation of Rhythm Management study.

BACKGROUND: Cardiac electric therapies effectively terminate tachyarrhythmias. Recent data suggest a possible increase in long-term mortality associated with implantable cardioverter-defibrillator shocks. Little is known about the association between external cardioversion episodes (ECVe) and long-term mortality. We sought to assess the safety of repeated ECVe with regard to cardiovascular mortality and morbidity. METHODS AND RESULTS: We analyzed the data of the 4060 patients from the AFFIRM (Atrial Fibrillation Follow-up Investigation of Rhythm Management) trial. In particular, associations of ECVe with all-cause mortality, cardiovascular mortality, and hospitalizations after ECVe were studied. Over an average follow-up of 3.5 years, 660 (16.3%) patients died, 331 (8.2%) from cardiovascular causes. A total of 207 (5.1%) and 1697 (41.8%) patients had low ejection fraction and nonparoxysmal atrial fibrillation, respectively; 2460 patients received no ECVe, whereas 1600 experienced ≥ 1 ECVe. Death occurred in 412 (16.7%), 196 (16.5%), 39 (13.5%), and 13 (10.4%) of patients with 0, 1, 2, and ≥ 3 ECVe, respectively. There was no significant association between ECVe and mortality within any of the 4 subgroups defined by ejection fraction and atrial fibrillation type, although myocardial infarction, coronary artery bypass graft, and digoxin were significantly associated with death (estimated hazard ratios, 1.65, 1.59, and 1.62, respectively; P < 0.0001). ECVe were associated with increased cardiac hospitalization reported at the next follow-up visit (39.3% versus 5.8%; estimated odds ratio, 1.39; P < 0.0001). CONCLUSIONS: In the AFFIRM study, there was no significant association between ECVe and long-term mortality, even though ECVe were associated with increased hospitalizations from cardiac causes. Digoxin, myocardial infarction, and coronary artery bypass graft were significantly associated with mortality.

Digoxin therapy: A persisting interest despite contrary winds.

Digoxin therapy is used to treat heart failure patients for more than 200 years. However, absence of effect on overall mortality found in the DIG study associated with frequent adverse effects due to overdosing in elderly patients with impaired renal function finally persuaded medical opinion to the weak interest of digoxin in chronic heart failure. Its image of old-fashioned drug in the mind of young cardiology generations appears widely distorted, and suffers from the absence of promotion by pharmaceutical industry, given a very low cost and a rapid arrival onto the generic market. Yet, regarding strict data from the literature, it remains a lot of positive factors in favor of the interest for digoxin: reduction of morbidity, reduction of mortality at low serum concentration <1.0 ng/ml, very low cost with favorable cost-effectiveness ratio. This article challenges some arguments for defending digoxin as another first-line therapy as well as ACE inhibitors and beta-blockers in the treatment of chronic heart failure.

Pharmacologic prophylaxis of postoperative atrial fibrillation in patients undergoing cardiac surgery: beyond beta-blockers.

Postoperative atrial fibrillation (POAF) is a frequent complication of cardiac surgery that increases patient morbidity, length of stay, and hospital costs. A substantial body of evidence exists evaluating various pharmacologic and nonpharmacologic methods to decrease the occurrence of POAF in an effort to decrease its burden on the health care system. Evidence-based guidelines support the use of beta-blockers as standard prophylaxis of POAF in patients undergoing cardiac surgery. Traditional prophylactic therapy for POAF targets the sympathetic nervous system, refractory period, and atrial conduction. However, associations between the development of POAF and the inflammatory process, oxidative stress, and atrial remodeling have prompted the investigation of novel therapies targeting these processes. To evaluate the role of pharmacologic strategies beyond beta-blockers in the prevention of POAF, we conducted a search of the PubMed database to identify studies published from 1950-February 2009. Emphasis was placed on how these therapies could be used in patients intolerant to beta-blockers or as additive therapy in high-risk patients. We found that sufficient evidence exists to recommend the use of amiodarone, sotalol, and possibly magnesium as monotherapy in patients unable to take beta-blockers or as add-on therapy for the prevention of POAF. Currently, available evidence does not support the use of propafenone, procainamide, digoxin, thiazolidinediones, triiodothyronine, or calcium channel blockers in the prevention of POAF. Preliminary evidence suggests that dofetilide, angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers, 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins), nonsteroidal antiinflammatory drugs, corticosteroids, omega-3 fatty acids, ascorbic acid, N-acetylcysteine, and sodium nitroprusside may be effective in preventing POAF. Additional large-scale, adequately powered clinical studies are needed to determine the benefit of these agents before they can be considered for routine use.