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161. Digoxin in patients with atrial fibrillation and heart failure: A meta-analysis. (PubMed)

Digoxin in patients with atrial fibrillation and heart failure: A meta-analysis. 25900519 2016 04 22 2016 05 26 1874-1754 188 2015 Jun 01 International journal of cardiology Int. J. Cardiol. Digoxin in patients with atrial fibrillation and heart failure: A meta-analysis. 99-101 10.1016/j.ijcard.2015.04.031 S0167-5273(15)00750-0 Bavishi Chirag C Mount Sinai St. Luke's & Roosevelt Hospitals, New York, NY, USA. Electronic address: chiragpbavishi@gmail.com. Khan Abdur Rahman AR University of Toledo (...) Medical Center, Toledo, OH, USA. Ather Sameer S University of Alabama at Birmingham, Birmingham, AL, USA. eng Letter Meta-Analysis Review 2015 04 06 Netherlands Int J Cardiol 8200291 0167-5273 0 Anti-Arrhythmia Agents 73K4184T59 Digoxin IM Int J Cardiol. 2016 Mar 1;206:171-2 26805390 Int J Cardiol. 2016 Mar 1;206:56-7 26774832 Anti-Arrhythmia Agents administration & dosage Atrial Fibrillation diagnosis drug therapy epidemiology Digoxin administration & dosage adverse effects Female Follow-Up Studies

2015 International journal of cardiology

162. Digoxin-associated mortality: a systematic review and meta-analysis of the literature. (Full text)

Digoxin-associated mortality: a systematic review and meta-analysis of the literature. There are conflicting data regarding the effect of digoxin use on mortality in patients with atrial fibrillation (AF) or with congestive heart failure (CHF). The aim of this meta-analysis was to provide detailed analysis of the currently available study reports. We performed a MEDLINE and a COCHRANE search (1993-2014) of the English literature dealing with the effects of digoxin on all-cause-mortality (...) in subjects with AF or CHF. Only full-sized articles published in peer-reviewed journals were considered for this meta-analysis. A total of 19 reports were identified. Nine reports dealt with AF patients, seven with patients suffering from CHF, and three with both clinical conditions. Based on the analysis of adjusted mortality results of all 19 studies comprising 326 426 patients, digoxin use was associated with an increased relative risk of all-cause mortality [Hazard ratio (HR) 1.21, 95% confidence

2015 European Heart Journal PubMed

163. PP087. Deep trial secondary analysis: Digoxin immune fab fragment treatment has additional benefits in endogenous digitalis-like factor positive preeclamptic women. (PubMed)

PP087. Deep trial secondary analysis: Digoxin immune fab fragment treatment has additional benefits in endogenous digitalis-like factor positive preeclamptic women. A double blinded placebo controlled clinical trial of a commercial digoxin immune Fab fragment (DIF) in preeclamptic (PE) women provided some benefit to treated subjects (1). In that study DIF, relative to placebo, prevented a decline in CrCl and lowered levels of endogenous digitalis-like factor (EDLF) activity as measured

2015 Pregnancy Hypertension

164. Digoxin Therapy and Associated Clinical Outcomes in the MADIT-CRT Trial. (PubMed)

Digoxin Therapy and Associated Clinical Outcomes in the MADIT-CRT Trial. Digoxin's pharmacological, hemodynamic, and electrophysiological properties are well understood. However, in modern heart failure (HF) treatment, its effect has yet to be fully investigated.The aim of the present study was to determine the effects of digoxin on outcomes in patients with mild HF implanted with an implantable cardioverter-defibrillator (ICD) or cardiac resynchronization therapy with defibrillator (CRT-D (...) ) device.We investigated the effect of digoxin treatment on the end points of HF/death, HF alone, death alone, and ventricular tachycardia or ventricular fibrillation (VT/VF) in 1820 patients with mild HF (New York Heart Association class I and II), prolonged QRS duration (≥130 ms), and reduced left ventricular ejection fraction (≤30%) enrolled in the Multicenter Automatic Defibrillator Implantation Trial - Cardiac Resynchronization Therapy trial. Multivariate Cox proportional hazards regression models

2015 Heart rhythm : the official journal of the Heart Rhythm Society

165. The use of digoxin in patients with worsening chronic heart failure: reconsidering an old drug to reduce hospital admissions. (Full text)

The use of digoxin in patients with worsening chronic heart failure: reconsidering an old drug to reduce hospital admissions. Digoxin is the oldest cardiac drug still in contemporary use, yet its role in the management of patients with heart failure (HF) remains controversial. A purified cardiac glycoside derived from the foxglove plant, digoxin increases ejection fraction, augments cardiac output, and reduces pulmonary capillary wedge pressure without causing deleterious increases in heart (...) rate or decreases in blood pressure. Moreover, it is also a neurohormonal modulator at low doses. In the pivotal DIG (Digitalis Investigation Group) trial, digoxin therapy was shown to reduce all-cause and HF-specific hospitalizations but had no effect on survival. With the discovery of neurohormonal blockers capable of reducing mortality in HF with reduced ejection fraction, the results of the DIG trial were viewed as neutral, and the use of digoxin declined precipitously. Although modern drug

2014 Journal of the American College of Cardiology PubMed

166. Interaction between digoxin and dronedarone in the PALLAS trial. (Full text)

Interaction between digoxin and dronedarone in the PALLAS trial. Elevated serum digoxin concentration can cause toxicity, including death. Dronedarone increases digoxin concentration by P-glycoprotein interaction. In Permanent Atrial Fibrillation Outcome Study Using Dronedarone On Top Of Standard Therapy Trial (PALLAS), dronedarone was associated with both increased cardiovascular death and heart failure in patients with permanent atrial fibrillation. The present analysis examines whether (...) the dronedarone-digoxin interaction might explain these adverse outcomes.Subgroup analysis was performed to compare outcomes of patients on digoxin at baseline or not. In PALLAS, 1619 patients were randomized to dronedarone and 1617 to placebo, of whom 544 (33.6%) and 526 (32.5%) were receiving digoxin, respectively. Median (Q1,Q3) digoxin serum concentration on day 7 was 1.1 (0.7,1.5) ng/mL on dronedarone and 0.7 (0.5,1.1) ng/mL on placebo (P<0.001). Among patients on digoxin, there were 15 (8.6%/year

2014 Circulation. Arrhythmia and electrophysiology PubMed

167. Comparative effectiveness of digoxin and propranolol for supraventricular tachycardia in infants. (Full text)

Comparative effectiveness of digoxin and propranolol for supraventricular tachycardia in infants. Supraventricular tachycardia is the most common arrhythmia in infants, and antiarrhythmic medications are frequently used for prophylaxis. The optimal prophylactic antiarrhythmic medication is unknown, and prior randomized trials have been underpowered. We used data from a large clinical registry to compare efficacy and safety of digoxin and propranolol for infant supraventricular tachycardia (...) prophylaxis. We hypothesized that supraventricular tachycardia recurrence is less common on digoxin when compared with propranolol.Retrospective cohort study.Pediatrix Medical Group neonatal ICUs.Infants discharged from 1998 to 2012 with supraventricular tachycardia who were treated with digoxin or propranolol. We excluded infants discharged before completing 2 days of therapy, those with Wolff-Parkinson-White syndrome, structural heart defects (except atrial/ventricular septal defects and patent ductus

2014 Pediatric Critical Care Medicine PubMed

168. Digoxin and 30-day all-cause hospital admission in older patients with chronic diastolic heart failure. (Full text)

Digoxin and 30-day all-cause hospital admission in older patients with chronic diastolic heart failure. In the main Digitalis Investigation Group (DIG) trial, digoxin reduced the risk of 30-day all-cause hospitalization in older systolic heart failure patients. However, this effect has not been studied in older diastolic heart failure patients.In the ancillary DIG trial, of the 988 patients with chronic heart failure and preserved (> 45%) ejection fraction, 631 were age ≥ 65 years (mean age 73 (...) years, 45% women, 12% non-whites), of whom 311 received digoxin.All-cause hospitalization 30-day post randomization occurred in 4% of patients in the placebo group and 9% each among those in the digoxin group receiving 0.125 mg and ≥ 0.25 mg a day dosage (P = .026). Hazard ratios (HR) and 95% confidence intervals (CI) for digoxin use overall for 30-day, 3-month, and 12-month all-cause hospitalizations were 2.46 (1.25-4.83), 1.45 (0.96-2.20) and 1.14 (0.89-1.46), respectively. There was one 30-day

2014 American Journal of Medicine PubMed

169. Pharmacokinetics and pharmacodynamics of dabigatran etexilate, an oral direct thrombin inhibitor, with coadministration of digoxin. (PubMed)

Pharmacokinetics and pharmacodynamics of dabigatran etexilate, an oral direct thrombin inhibitor, with coadministration of digoxin. This study evaluated the potential impact of concomitant digoxin on the pharmacokinetics and pharmacodynamics of dabigatran etexilate, a novel oral direct thrombin inhibitor. Healthy volunteers (n = 23) received 150 mg dabigatran etexilate twice daily on days 1 to 3 and once on day 4 in 1 period. Digoxin was given in another period as a loading dose of 0.5 mg early (...) on day 1 and 0.25 mg in the evening of day 1 and on the mornings of days 2 to 4. In a third treatment period, dabigatran etexilate together with digoxin was given on days 1 to 4. Exposure to dabigatran was not significantly altered with concomitant digoxin-the maximum concentration (Cmax,ss ) and area under the concentration-time curve at steady state over 1 dosing interval (AUCτ,ss ) of dabigatran with and without digoxin were essentially unchanged. The pharmacokinetic profile of digoxin also

2014 Journal of clinical pharmacology

170. Darexaban (YM150), an oral direct factor Xa inhibitor, has no effect on the pharmacokinetics of digoxin. (PubMed)

Darexaban (YM150), an oral direct factor Xa inhibitor, has no effect on the pharmacokinetics of digoxin. To investigate the impact of the direct Factor Xa inhibitor darexaban administered in a modified-release formulation (darexaban-MR) on the pharmacokinetic (PK) profile of digoxin. In this Phase I, randomized, double-blind, two-period crossover study (8 days for each treatment, 10 days washout), 24 healthy subjects received darexaban-MR 120 mg once/day (qd) + digoxin 0.25 mg qd in one (...) treatment period, and placebo + digoxin 0.25 mg qd in the other treatment period. Blood for PK assessment of digoxin and darexaban was obtained in serial profile on day 8, as well as pre-dose on day 6-7; urinary PK samples were obtained up to 24 h after the last dose on day 8. A lack of interaction was determined if 90 % confidence intervals (CIs) for the geometric mean ratios (GMR) of digoxin C max,ss and AUC0-24h,ss with and without darexaban-MR co-administration were within 0.80-1.25 limits

2014 European journal of drug metabolism and pharmacokinetics

171. Absence of pharmacokinetic interaction between roflumilast and digoxin in healthy adults. (PubMed)

Absence of pharmacokinetic interaction between roflumilast and digoxin in healthy adults. Numerous interactions are known for digoxin, which is a drug with a narrow therapeutic index and a substrate of P-glycoprotein (P-gp). This study investigated potential effects of coadministration on pharmacokinetics and safety of both drugs when a single dose of digoxin was concomitantly administered with roflumilast under steady-state conditions. Sixteen healthy male and female adults were randomly (...) assigned in an open-label, crossover study to either of 2 treatment sequences that consisted of 2 treatment periods separated by a washout phase. Treatments were oral daily doses of roflumilast for 14 days given concomitantly on days 1 and 14 with a single oral dose of digoxin or an oral dose of digoxin once on day 1. Plasma samples for pharmacokinetic evaluations of digoxin and roflumilast concentrations with and without concomitant treatment were taken. The rate of digoxin absorption was slightly (15

2014 Journal of clinical pharmacology

172. Comparison between ivabradine and low-dose digoxin in the therapy of diastolic heart failure with preserved left ventricular systolic function. (Full text)

Comparison between ivabradine and low-dose digoxin in the therapy of diastolic heart failure with preserved left ventricular systolic function. Multicenter trials have demonstrated that in patients with sinus rhythm ivabradine is effective in the therapy of ischemic heart disease and of impaired left ventricular systolic function. Ivabradine is ineffective in atrial fibrillation. Many patients with symptomatic heart failure have diastolic dysfunction with preserved left ventricular systolic (...) function, and many have asymptomatic paroxysmal atrial fibrillation. Ivabradine is not indicated in these conditions, but it happens that it is erroneously used. Digoxin is now considered an outdated and potentially dangerous drug and while effective in the mentioned conditions, is rarely used. The aim of the study was to compare the therapeutic effects of ivabradine in diastolic heart failure with preserved left ventricular systolic function. Patients were assigned to ivabradine or digoxin according

2014 Clinics and practice PubMed

173. Inhibiting the Th17/IL-17A-Related Inflammatory Responses With Digoxin Confers Protection Against Experimental Abdominal Aortic Aneurysm. (Full text)

Inhibiting the Th17/IL-17A-Related Inflammatory Responses With Digoxin Confers Protection Against Experimental Abdominal Aortic Aneurysm. T helper 17 cells and interleukin-17A have been implicated in the progression of abdominal aortic aneurysm (AAA). Retinoic acid-related orphan receptor gamma thymus, the master transcription factor of T helper 17 cell differentiation, is selectively antagonized by digoxin. However, the effect of antagonizing retinoic acid-related orphan receptor gamma thymus (...) digoxin, 20 μg/d per mouse), and high-dose group (Ang II+high-dose digoxin, 40 μg/d per mouse). All treatments began on day 0 after surgery. Efficacy was determined via aortic diameter and systolic blood pressure measurements, histopathology and protein expression, and flow cytometry analysis when euthenized. Human aortic tissue analysis showed that both interleukin-17A and retinoic acid-related orphan receptor gamma thymus increased in AAA tissues. The low-dose and high-dose groups had AAA incidences

2014 Thrombosis and Vascular Biology PubMed

174. Use of a Simplified Nomogram to Individualize Digoxin Dosing versus Standard Dosing Practices in Patients with Heart Failure. (Full text)

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

2014 Pharmacotherapy PubMed

175. Relation of Digoxin Use in Atrial Fibrillation and the Risk of All-Cause Mortality in Patients ≥65 Years of Age With Versus Without Heart Failure. (PubMed)

Relation of Digoxin Use in Atrial Fibrillation and the Risk of All-Cause Mortality in Patients ≥65 Years of Age With Versus Without Heart Failure. Previous studies on digoxin use in patients with atrial fibrillation (AF) and the risk of all-cause mortality found conflicting results. We conducted a population-based, retrospective, cohort study of patients aged ≥65 years admitted to a hospital with a primary or secondary diagnosis of AF, in Quebec province, Canada, from 1998 to 2012. The AF (...) cohort was grouped into patients with and without heart failure (HF) and into digoxin and no-digoxin users according to the first prescription filled for digoxin within 30 days after AF hospital discharge. We derived propensity score-matched digoxin and no-digoxin treatment groups for the groups of patients with and without HF, respectively, and conducted multivariable Cox proportional hazards regression analyses to determine association between digoxin use and all-cause mortality. The AF propensity

2014 The American journal of cardiology

176. Effect of Lacosamide on the Steady-State Pharmacokinetics of Digoxin: Results from a Phase I, Multiple-Dose, Double-Blind, Randomised, Placebo-Controlled, Crossover Trial. (PubMed)

Effect of Lacosamide on the Steady-State Pharmacokinetics of Digoxin: Results from a Phase I, Multiple-Dose, Double-Blind, Randomised, Placebo-Controlled, Crossover Trial. Recent data suggest that P-glycoprotein may be involved in cellular transport of lacosamide.To investigate potential drug-drug interactions (DDIs) between lacosamide and digoxin, this phase I, multiple-dose, randomised, double-blind, placebo-controlled, crossover trial assessed the pharmacokinetics, pharmacodynamics, safety (...) and tolerability of digoxin administered in combination with lacosamide or placebo.Twenty healthy White male volunteers were randomised. After receiving digoxin 0.25 mg three times daily on day 1 (loading dose), participants received digoxin 0.25 mg once daily on days 2-22. Participants received either lacosamide (200 mg twice daily) or placebo on days 8-11 and vice versa on days 18-21, after a 6-day washout. The steady-state area under concentration-time curve over the dosing interval (AUC(24,ss)) and maximum

2014 Clinical drug investigation

177. Digoxin Induced Reversible Dysfunction of the Cone Photoreceptors in Monkeys. (Full text)

Digoxin Induced Reversible Dysfunction of the Cone Photoreceptors in Monkeys. To investigate functional alteration of the retina induced by digoxin in monkeys.Digoxin was intravenously administered to cynomolgus monkeys and standard full-field electroretinograms (ERGs) were serially recorded. In other digoxin-treated monkeys, the rod and cone a-waves to high-intensity flashes were obtained and analyzed by the a-wave fitting model (a-wave analysis). The following responses were also recorded (...) : dark- and light-adapted responses to flashes of different intensities (dark- and light-adapted luminance responses), photopic ERG elicited by long-duration stimulus (ON-OFF response), and the photopic negative response (PhNR).Delayed b-wave was observed in all responses of the standard full-field ERGs; amplitude of the b-wave was increased in the rod response, but was decreased in the single-flash cone response and the 30-Hz flicker. These changes recovered gradually after elimination of digoxin

2014 Investigative Ophthalmology & Visual Science PubMed

178. Digoxin and 30-day All-cause Hospital Admission in Older Patients with Chronic Diastolic Heart Failure. (Full text)

Digoxin and 30-day All-cause Hospital Admission in Older Patients with Chronic Diastolic Heart Failure. In the main Digitalis Investigation Group (DIG) trial, digoxin reduced the risk of 30-day all-cause hospitalization in older systolic heart failure patients. However, this effect has not been studied in older diastolic heart failure patients.In the ancillary DIG trial, of the 988 patients with chronic heart failure and preserved (> 45%) ejection fraction, 631 were age ≥ 65 years (mean age 73 (...) years, 45% women, 12% non-whites), of whom 311 received digoxin.All-cause hospitalization 30-day post randomization occurred in 4% of patients in the placebo group and 9% each among those in the digoxin group receiving 0.125 mg and ≥ 0.25 mg a day dosage (P = .026). Hazard ratios (HR) and 95% confidence intervals (CI) for digoxin use overall for 30-day, 3-month, and 12-month all-cause hospitalizations were 2.46 (1.25-4.83), 1.45 (0.96-2.20) and 1.14 (0.89-1.46), respectively. There was one 30-day

2014 The American journal of medicine PubMed

179. The effect of single- and multiple-dose etravirine on a drug cocktail of representative cytochrome P450 probes and digoxin in healthy subjects. (PubMed)

The effect of single- and multiple-dose etravirine on a drug cocktail of representative cytochrome P450 probes and digoxin in healthy subjects. The effect of etravirine on cytochrome P450 (CYP) enzymes and P-glycoprotein were evaluated in two randomized, crossover trials in healthy subjects. A modified Cooperstown 5 + 1 cocktail was utilized to determine the effects of etravirine on single-dose pharmacokinetics of model CYP probes. The cocktail was administered alone, then, after a 14-day (...) washout, etravirine 200 mg twice daily (bid) was given for 14 days with cocktail on days 1 and 14. In a separate study, digoxin (0.5 mg) was administered alone, then, after a 14-day washout, etravirine 200 mg bid was administered for 12 days with digoxin on day 8. In the cocktail study, the AUClast least squares mean (LSM) ratios (90% confidence intervals [CIs]) for cocktail + etravirine versus cocktail were 0.93 (0.88, 0.99; paraxanthine), 0.58 (0.44, 0.75; 7-OH-S-warfarin), 0.43 (0.20, 0.96; 5-OH

2014 Journal of clinical pharmacology

180. Digoxin in Patients with Permanent Atrial Fibrillation: Data from the RACE II Study. (PubMed)

Digoxin in Patients with Permanent Atrial Fibrillation: Data from the RACE II Study. The Atrial Fibrillation Follow-up Investigation of Rhythm Management trial showed that digoxin was associated with increased mortality in patients with atrial fibrillation.To assess the association of digoxin with cardiovascular (CV) morbidity and mortality in patients with permanent atrial fibrillation enrolled in the Dutch Rate Control Efficacy in Permanent AF: A Comparison Between Lenient Versus Strict Rate (...) Control II trial as well as to assess the role of digoxin to achieve heart rate targets.The primary outcome was a composite of CV morbidity and mortality. Secondary outcomes included CV hospitalization and all-cause mortality or heart failure (HF) hospitalization. Of the 614 patients, 608 (99%) completed the dose-adjustment phase. Outcome events were analyzed from the end of the dose-adjustment phase until the end of follow-up. The median follow-up period was 2.9 years (interquartile range 2.7-3.0

2014 Heart rhythm : the official journal of the Heart Rhythm Society

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