digoxin and Stroke

Cardiovascular diseases are a leading cause of morbidity and mortality in most developed countries of the world. Pharmaceuticals, illicit drugs, and toxins can significantly contribute to the overall cardiovascular burden and thus deserve attention. The present article is a systematic overview of drugs that may induce distinct cardiovascular toxicity. The compounds are classified into agents that have significant effects on the heart, blood vessels, or both. The mechanism(s) of toxic action are discussed and treatment modalities are briefly mentioned in relevant cases. Due to the large number of clinically relevant compounds discussed, this article could be of interest to a broad audience including pharmacologists and toxicologists, pharmacists, physicians, and medicinal chemists. Particular emphasis is given to clinically relevant topics including the cardiovascular toxicity of illicit sympathomimetic drugs (e.g., cocaine, amphetamines, cathinones), drugs that prolong the QT interval, antidysrhythmic drugs, digoxin and other cardioactive steroids, beta-blockers, calcium channel blockers, female hormones, nonsteroidal anti-inflammatory, and anticancer compounds encompassing anthracyclines and novel targeted therapy interfering with the HER2 or the vascular endothelial growth factor pathway.

Topics: Adrenergic beta-Antagonists; Alkaloids; Amphetamines; Animals; Anti-Arrhythmia Agents; Anti-Inflammatory Agents, Non-Steroidal; Antineoplastic Agents; Calcium Channel Blockers; Cardiovascular Diseases; Cardiovascular System; Cocaine; Digoxin; Female; Heart Rate; Hormones; Humans; Male; Steroids; Stroke; Vascular Endothelial Growth Factor A

During recent years, systematic reviews of observational studies have compared digoxin to no digoxin in patients with atrial fibrillation or atrial flutter, and the results of these reviews suggested that digoxin seems to increase the risk of all-cause mortality regardless of concomitant heart failure. Our objective was to assess the benefits and harms of digoxin for atrial fibrillation and atrial flutter based on randomized clinical trials.. We searched CENTRAL, MEDLINE, Embase, LILACS, SCI-Expanded, BIOSIS for eligible trials comparing digoxin versus placebo, no intervention, or other medical interventions in patients with atrial fibrillation or atrial flutter in October 2016. Our primary outcomes were all-cause mortality, serious adverse events, and quality of life. Our secondary outcomes were heart failure, stroke, heart rate control, and conversion to sinus rhythm. We performed both random-effects and fixed-effect meta-analyses and chose the more conservative result as our primary result. We used Trial Sequential Analysis (TSA) to control for random errors. We used GRADE to assess the quality of the body of evidence.. 28 trials (n = 2223 participants) were included. All were at high risk of bias and reported only short-term follow-up. When digoxin was compared with all control interventions in one analysis, we found no evidence of a difference on all-cause mortality (risk ratio (RR), 0.82; TSA-adjusted confidence interval (CI), 0.02 to 31.2; I2 = 0%); serious adverse events (RR, 1.65; TSA-adjusted CI, 0.24 to 11.5; I2 = 0%); quality of life; heart failure (RR, 1.05; TSA-adjusted CI, 0.00 to 1141.8; I2 = 51%); and stroke (RR, 2.27; TSA-adjusted CI, 0.00 to 7887.3; I2 = 17%). Our analyses on acute heart rate control (within 6 hours of treatment onset) showed firm evidence of digoxin being superior compared with placebo (mean difference (MD), -12.0 beats per minute (bpm); TSA-adjusted CI, -17.2 to -6.76; I2 = 0%) and inferior compared with beta blockers (MD, 20.7 bpm; TSA-adjusted CI, 14.2 to 27.2; I2 = 0%). Meta-analyses on acute heart rate control showed that digoxin was inferior compared with both calcium antagonists (MD, 21.0 bpm; TSA-adjusted CI, -30.3 to 72.3) and with amiodarone (MD, 14.7 bpm; TSA-adjusted CI, -0.58 to 30.0; I2 = 42%), but in both comparisons TSAs showed that we lacked information. Meta-analysis on acute conversion to sinus rhythm showed that digoxin compared with amiodarone reduced the probability of converting atrial fibrillation to sinus rhythm, but TSA showed that we lacked information (RR, 0.54; TSA-adjusted CI, 0.13 to 2.21; I2 = 0%).. The clinical effects of digoxin on all-cause mortality, serious adverse events, quality of life, heart failure, and stroke are unclear based on current evidence. Digoxin seems to be superior compared with placebo in reducing the heart rate, but inferior compared with beta blockers. The long-term effect of digoxin is unclear, as no trials reported long-term follow-up. More trials at low risk of bias and low risk of random errors assessing the clinical effects of digoxin are needed.. PROSPERO CRD42016052935.

Topics: Aged; Amiodarone; Atrial Fibrillation; Atrial Flutter; Bias; Calcium Channel Blockers; Comorbidity; Digoxin; Female; Heart Failure; Heart Rate; Humans; Male; Middle Aged; Mortality; Quality of Life; Randomized Controlled Trials as Topic; Research Design; Stroke; Treatment Outcome

Topics: Adrenergic beta-Antagonists; Anticoagulants; Atrial Fibrillation; Catheter Ablation; Digoxin; Humans; Incidence; Kidney Failure, Chronic; Randomized Controlled Trials as Topic; Renal Dialysis; Risk Factors; Stroke; Thromboembolism

The Canadian Cardiovascular Society (CCS) Atrial Fibrillation (AF) Guidelines Committee provides periodic reviews of new data to produce focused updates that address clinically important advances in AF management. This 2016 Focused Update deals with: (1) the management of antithrombotic therapy for AF patients in the context of the various clinical presentations of coronary artery disease; (2) real-life data with non-vitamin K antagonist oral anticoagulants; (3) the use of antidotes for the reversal of non-vitamin K antagonist oral anticoagulants; (4) digoxin as a rate control agent; (5) perioperative anticoagulation management; and (6) AF surgical therapy including the prevention and treatment of AF after cardiac surgery. The recommendations were developed with the same methodology used for the initial 2010 guidelines and the 2012 and 2014 Focused Updates. Using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) standards, individual studies and literature were reviewed for quality and bias; the literature review process and evidence tables are included in the Supplementary Material, and on the CCS Web site. The section on concomitant AF and coronary artery disease was developed in collaboration with the CCS Antiplatelet Guidelines Committee. Details of the updated recommendations are presented, along with their background and rationale. This document is linked to an updated summary of all CCS AF Guidelines recommendations, from 2010 to the present 2016 Focused Update.

Topics: Acute Coronary Syndrome; Algorithms; Anticoagulants; Atrial Appendage; Atrial Fibrillation; Cardiac Pacing, Artificial; Cardiotonic Agents; Catheter Ablation; Coronary Artery Disease; Digoxin; Drug Therapy, Combination; Factor Xa Inhibitors; Fibrinolytic Agents; Hemorrhage; Humans; Magnesium; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Postoperative Complications; ST Elevation Myocardial Infarction; Stroke

Atrial fibrillation (AF) is common and causes impaired quality of life, an increased risk of stroke and death as well as frequent hospital admissions. The majority of patients with AF require control of heart rate. In this article , we summarise the limited evidence from clinical trials that guides prescription, and present the rationale and protocol for a new randomised trial. As rate control has not yet been shown to reduce mortality, there is a clear need to compare the impact of therapy on quality of life, cardiac function and exercise capacity. Such a trial should concentrate on the long-term effects of treatment in the largest proportion of patients with AF, those with symptomatic permanent AF, with the aim of improving patient well-being.. The RAte control Therapy Evaluation in permanent Atrial Fibrillation (RATE-AF) trial will enrol 160 participants with a prospective, randomised, open-label, blinded end point design comparing initial rate control with digoxin or bisoprolol. This will be the first head-to-head randomised trial of digoxin and beta-blockers in AF.. Recruited patients will be aged ≥60 years with permanent AF and symptoms of breathlessness (equivalent to New York Heart Association class II or above), with few exclusion criteria to maximise generalisability to routine clinical practice.. The primary outcome is patient-reported quality of life, with secondary outcomes including echocardiographic ventricular function, exercise capacity and biomarkers of cellular and clinical response. Follow-up will occur at 6 and 12 months, with feasibility components to inform the design of a future trial powered to detect a difference in hospital admission. The RATE-AF trial will underpin an integrated approach to management including biomarkers, functions and symptoms that will guide future research into optimal, personalised rate control in patients with AF.. East Midlands-Derby Research Ethics Committee (16/EM/0178); peer-reviewed publications.. Clinicaltrials.gov: NCT02391337; ISRCTN: 95259705. Pre-results.

Topics: Adrenergic beta-1 Receptor Antagonists; Aged; Anti-Arrhythmia Agents; Atrial Fibrillation; Bisoprolol; Digoxin; Female; Heart Failure; Heart Rate; Hospitalization; Humans; Male; Middle Aged; Prospective Studies; Quality of Life; Research Design; Stroke; Time; United Kingdom

Although inappropriate use of digoxin has been described in various populations, a real-world evaluation of patterns of digoxin prescription has not been well studied in patients with atrial fibrillation (AF). The aim of this study was to identify prevalence, indications and appropriateness of digoxin use in the general population of patients with non-valvular AF (NVAF) in Turkey.. We included and classified patients from the RAMSES (ReAl-life Multicentre Survey Evaluating Stroke prevention strategies in Turkey) study, a prospective registry including 6273 patients with NVAF, on the basis of digoxin use. After excluding the data of 73 patients whose medical history about digoxin use or left ventricle function was absent, 6200 patients were included for the final analysis. Digoxin use was considered inappropriate if patients did not have left ventricular systolic dysfunction or symptomatic heart failure (HF).. Digoxin was used in 1274 (20·5%) patients. Patients treated with digoxin were older (71·4 ± 9·8 years vs. 69·2 ± 10·9 years, P < 0·001), more likely to be female (58·8% vs. 55·9%, P = 0·019) and had more common comorbidities such as HF (40·2% vs. 17·4%), diabetes (26·4% vs. 21·1%), coronary artery disease (35·3 vs. 27·6%) and persistent/permanent AF (93·4% vs. 78·4%; P < 0·001 for each comparison). Of the 1274 patients, the indication of digoxin use was considered inappropriate in 762 (59·8%).. Our findings show that nearly one-fifth of the patients with NVAF were on digoxin therapy and nearly 60% of these patients were receiving digoxin with inappropriate indications in a real-world setting.

Topics: Aged; Atrial Fibrillation; Comorbidity; Digoxin; Female; Heart Failure; Heart Ventricles; Humans; Male; Prospective Studies; Stroke; Turkey

Topics: Aged; Anti-Arrhythmia Agents; Atrial Fibrillation; Cohort Studies; Digoxin; Female; Follow-Up Studies; Humans; Longitudinal Studies; Male; Middle Aged; Population Surveillance; Risk Factors; Stroke

Dronedarone restores sinus rhythm and reduces hospitalization or death in intermittent atrial fibrillation. It also lowers heart rate and blood pressure and has antiadrenergic and potential ventricular antiarrhythmic effects. We hypothesized that dronedarone would reduce major vascular events in high-risk permanent atrial fibrillation.. We assigned patients who were at least 65 years of age with at least a 6-month history of permanent atrial fibrillation and risk factors for major vascular events to receive dronedarone or placebo. The first coprimary outcome was stroke, myocardial infarction, systemic embolism, or death from cardiovascular causes. The second coprimary outcome was unplanned hospitalization for a cardiovascular cause or death.. After the enrollment of 3236 patients, the study was stopped for safety reasons. The first coprimary outcome occurred in 43 patients receiving dronedarone and 19 receiving placebo (hazard ratio, 2.29; 95% confidence interval [CI], 1.34 to 3.94; P=0.002). There were 21 deaths from cardiovascular causes in the dronedarone group and 10 in the placebo group (hazard ratio, 2.11; 95% CI, 1.00 to 4.49; P=0.046), including death from arrhythmia in 13 patients and 4 patients, respectively (hazard ratio, 3.26; 95% CI, 1.06 to 10.00; P=0.03). Stroke occurred in 23 patients in the dronedarone group and 10 in the placebo group (hazard ratio, 2.32; 95% CI, 1.11 to 4.88; P=0.02). Hospitalization for heart failure occurred in 43 patients in the dronedarone group and 24 in the placebo group (hazard ratio, 1.81; 95% CI, 1.10 to 2.99; P=0.02).. Dronedarone increased rates of heart failure, stroke, and death from cardiovascular causes in patients with permanent atrial fibrillation who were at risk for major vascular events. Our data show that this drug should not be used in such patients. (Funded by Sanofi-Aventis; PALLAS ClinicalTrials.gov number, NCT01151137.).

Topics: Aged; Aged, 80 and over; Amiodarone; Anti-Arrhythmia Agents; Atrial Fibrillation; Atrial Flutter; Cardiovascular Diseases; Chronic Disease; Digoxin; Double-Blind Method; Dronedarone; Drug Therapy, Combination; Female; Follow-Up Studies; Heart Failure; Heart Rate; Hospitalization; Humans; Male; Risk Factors; Stroke

The AFFIRM Study showed that treatment of patients with atrial fibrillation and a high risk for stroke or death with a rhythm-control strategy offered no survival advantage over a rate-control strategy in an intention-to-treat analysis. This article reports an "on-treatment" analysis of the relationship of survival to cardiac rhythm and treatment as they changed over time.. Modeling techniques were used to determine the relationships among survival, baseline clinical variables, and time-dependent variables. The following baseline variables were significantly associated with an increased risk of death: increasing age, coronary artery disease, congestive heart failure, diabetes, stroke or transient ischemic attack, smoking, left ventricular dysfunction, and mitral regurgitation. Among the time-dependent variables, the presence of sinus rhythm (SR) was associated with a lower risk of death, as was warfarin use. Antiarrhythmic drugs (AADs) were associated with increased mortality only after adjustment for the presence of SR. Consistent with the original intention-to-treat analysis, AADs were no longer associated with mortality when SR was removed from the model.. Warfarin use improves survival. SR is either an important determinant of survival or a marker for other factors associated with survival that were not recorded, determined, or included in the survival model. Currently available AADs are not associated with improved survival, which suggests that any beneficial antiarrhythmic effects of AADs are offset by their adverse effects. If an effective method for maintaining SR with fewer adverse effects were available, it might be beneficial.

Topics: Adrenergic beta-Antagonists; Amiodarone; Anti-Arrhythmia Agents; Anticoagulants; Atrial Fibrillation; Calcium Channel Blockers; Combined Modality Therapy; Comorbidity; Digoxin; Electric Countershock; Follow-Up Studies; Heart Rate; Humans; Models, Cardiovascular; Myocardial Contraction; Phenethylamines; Proportional Hazards Models; Retrospective Studies; Risk; Stroke; Sulfonamides; Survival Analysis; Treatment Failure; Treatment Outcome; Warfarin

The incidence, predictive factors, morbidity, and mortality associated with the development of supraventricular tachyarrhythmias (SVTs) in patients with congestive heart failure (CHF) are poorly defined.. In the Digitalis Investigation Group trial, patients with CHF who were in sinus rhythm were randomly assigned to digoxin (n = 3,889) or placebo (n = 3,899) and followed up for a mean of 37 months. Baseline factors that predicted the occurrence of SVT and the effects of SVT on total mortality, stroke, and hospitalization for worsening CHF were determined.. Eight hundred sixty-six patients (11.1%) had SVT during the study period. Older age (odds ratio [OR], 1.029 for each year increase in age; p = 0.0001), male sex (OR, 1.270; p = 0.0075), increasing duration of CHF (OR, 1.003 for each month increase in duration of CHF; p = 0.0021), and a cardiothoracic ratio of > 0.50 (OR, 1.403; p = 0.0001) predicted an increased risk of experiencing SVT. Left ventricular ejection fraction, New York Heart Association functional class, and treatment with digoxin vs placebo were not related to the occurrence of SVT. After adjustment for other risk factors, development of SVT predicted a greater risk of subsequent total mortality (risk ratio [RR] = 2.451; p = 0.0001), stroke (RR = 2.352; p = 0.0001), and hospitalization for worsening CHF (RR = 3. 004; p = 0.0001).. In CHF patients in sinus rhythm, older age, male sex, longer duration of CHF, and increased cardiothoracic ratio predict an increased risk for experiencing SVT. Development of SVT is a strong independent predictor of mortality, stroke, and hospitalization for CHF in this population. Prevention of SVT may prolong survival and reduce morbidity in CHF patients.

Topics: Age Factors; Aged; Cardiotonic Agents; Digoxin; Double-Blind Method; Female; Heart Failure; Heart Rate; Humans; Incidence; Male; Middle Aged; Odds Ratio; Prognosis; Sex Factors; Stroke; Stroke Volume; Survival Rate; Tachycardia, Supraventricular

Digoxin is used for rate control in atrial fibrillation (AF), but evidence for its efficacy and safety after myocardial infarction (MI) is scarce and mixed. We studied post-MI digoxin use effects on AF patient outcomes in a nationwide registry follow-up study in Finland. Digoxin was used by 18.6% of AF patients after MI, with a decreasing usage trend during 2004-2014. Baseline differences in digoxin users (n = 881) and controls (n = 3898) were balanced with inverse probability of treatment weight adjustment. The median follow-up was 7.4 years. Patients using digoxin after MI had a higher cumulative all-cause mortality (77.4% vs. 72.3%; hazard ratio [HR]: 1.19; confidence interval [CI]: 1.07-1.32; p = 0.001) during a 10-year follow-up. Mortality differences were detected in a subgroup analysis of patients without baseline heart failure (HF) (HR: 1.23; p = 0.019) but not in patients with baseline HF (HR: 1.05; p = 0.413). Cumulative incidences of HF hospitalizations, stroke and new MI were similar between digoxin group and controls. In conclusion, digoxin use after MI is associated with increased mortality but not with HF hospitalizations, new MI or stroke in AF patients. Increased mortality was detected in patients without baseline HF. Results suggest caution with digoxin after MI in AF patients, especially in the absence of HF.

Topics: Anti-Arrhythmia Agents; Atrial Fibrillation; Digoxin; Follow-Up Studies; Heart Failure; Humans; Myocardial Infarction; Risk Factors; Stroke

To determine the prognosis of Takayasu arteritis (TA) patients with moderate-to-severe aortic regurgitation treated with surgical vs conservative treatment and to identify independent prognostic factors of long-term outcomes.. Between January 2002 and January 2017, 101 consecutive TA patients with moderate-to-severe aortic regurgitation treated with either surgical (n = 38) or conservative (n = 63) treatments were investigated in this retrospective observational case-control study. The primary end point was all-cause mortality, and the secondary end point comprised the combined end points of death, non-fatal stroke and cardiac events (non-fatal myocardial infarction and congestive heart failure). Propensity score matching was used to reduce the bias of baseline risk factors.. The unadjusted all-cause 10-year mortality in the conservative group was increased compared with the surgical group (28.2% vs 7.4%; log-rank P = 0.036), and the combined end points showed the same trend (52.1% vs 25.3%; log-rank P = 0.005). After an adjustment of baseline risk factors, the conservative treatment was associated with reduced survival rates of both all-cause mortality [hazard ratio (HR): 8.243; 95% CI: 1.069, 63.552; P = 0.007] and combined end points (HR: 6.341; 95% CI: 1.469, 27.375; P = 0.002). Conservative treatment (HR: 3.838, 95% CI: 1.333, 11.053; P = 0.013) and left ventricular end-diastolic diameter (HR: 1.036, 95% CI: 1.001, 1.071; P = 0.042) were risk factors for increased combined end points.. Surgical treatment improves the outcomes of patients with moderate-to-severe aortic regurgitation due to TA. The dilated left ventricle indicated a worse prognosis.

Topics: Adrenergic beta-Antagonists; Adult; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Aorta; Aortic Valve Insufficiency; Calcium Channel Blockers; Cardiotonic Agents; Case-Control Studies; Cause of Death; Conservative Treatment; Digoxin; Female; Glucocorticoids; Heart Failure; Heart Valve Prosthesis Implantation; Humans; Immunosuppressive Agents; Male; Middle Aged; Mortality; Myocardial Infarction; Platelet Aggregation Inhibitors; Prednisone; Propensity Score; Retrospective Studies; Severity of Illness Index; Stroke; Takayasu Arteritis; Treatment Outcome

Topics: Aged; Anti-Arrhythmia Agents; Atrial Fibrillation; Digoxin; Humans; Male; Middle Aged; Prospective Studies; Risk Factors; Stroke

Congestive heart failure (CHF) is commonly associated with nonvalvular atrial fibrillation (AF), and their combination may affect treatment strategies and outcomes.. To assess the treatment strategies and 1-year clinical outcomes of antithrombotic and CHF therapies for patients with newly diagnosed AF with concomitant CHF stratified by etiology (ischemic cardiomyopathy [ICM] vs nonischemic cardiomyopathy [NICM]).. The GARFIELD-AF registry is a prospective, noninterventional registry. A total of 52 014 patients with AF were enrolled between March 2010 and August 2016. A total of 11 738 patients 18 years and older with newly diagnosed AF (≤6 weeks' duration) and at least 1 investigator-determined stroke risk factor were included. Data were analyzed from December 2017 to September 2018.. One-year follow-up rates of death, stroke/systemic embolism, and major bleeding were assessed.. Event rates per 100 person-years were estimated from the Poisson model and Cox hazard ratios (HRs) and 95% confidence intervals.. The median age of the population was 71.0 years, 22 987 of 52 013 were women (44.2%) and 31 958 of 52 014 were white (61.4%). Of 11 738 patients with CHF, 4717 (40.2%) had ICM and 7021 (59.8%) had NICM. Prescription of oral anticoagulant and antiplatelet drugs was not balanced between groups. Oral anticoagulants with or without antiplatelet drugs were used in 2753 patients with ICM (60.1%) and 5082 patients with NICM (73.7%). Antiplatelets were prescribed alone in 1576 patients with ICM (34.4%) and 1071 patients with NICM (15.5%). Compared with patients with NICM, use of angiotensin-converting enzyme inhibitors/angiotensin receptor blockers (72.6% [3439] vs 60.3% [4236]) and of β blockers (63.3% [2988] vs 53.2% [3737]) was higher in patients with ICM. Rates of all-cause and cardiovascular death per 100 patient-years were significantly higher in the ICM group (all-cause death: ICM, 10.2; 95% CI, 9.2-11.1; NICM, 7.0; 95% CI, 6.4-7.6; cardiovascular death: ICM, 5.1; 95% CI, 4.5-5.9; NICM, 2.9; 95% CI, 2.5-3.4). Stroke/systemic embolism rates tended to be higher in ICM groups compared with NICM groups (ICM, 2.0; 95% CI, 1.6-2.5; NICM, 1.5; 95% CI, 1.3-1.9). Major bleeding rates were significantly higher in the ICM group (1.1; 95% CI, 0.8-1.4) compared with the NICM group (0.7; 95% CI, 0.5-0.9).. Patients with ICM received oral anticoagulants with or without antiplatelet drugs less frequently and antiplatelets alone more frequently than patients with NICM, but they received angiotensin-converting enzyme inhibitors/angiotensin receptor blockers more often than patients with NICM. All-cause and cardiovascular death rates were higher in patients with ICM than patients with NICM.. ClinicalTrials.gov Identifier: NCT01090362.

Topics: Adrenergic beta-Antagonists; Aged; Aged, 80 and over; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Anticoagulants; Atrial Fibrillation; Cardiomyopathies; Cardiotonic Agents; Cardiovascular Diseases; Cohort Studies; Digoxin; Female; Guideline Adherence; Heart Failure; Hemorrhage; Humans; Male; Middle Aged; Mineralocorticoid Receptor Antagonists; Mortality; Myocardial Ischemia; Platelet Aggregation Inhibitors; Practice Guidelines as Topic; Proportional Hazards Models; Registries; Sodium Potassium Chloride Symporter Inhibitors; Stroke; Stroke Volume

Some evidences suggest that the use of digoxin may be harmful inatrial fibrillation (AF) patients. The aim of the study was to investigate in a "real world" of AF patients receiving vitamin K antagonists (VKAs), the relationship between digoxin use and mortality.. Prospective single-center observational study including 815 consecutive non-valvular AF patients treated with VKAs. Total mortality was the primary outcome of the study. We also performed a sub-analysis considering only cardiovascular (CV) deaths. Time in therapeutic range (TTR) was used for anticoagulation quality.. Median follow-up was 33.2months (2460 person-years); 171 (21.0%) patients were taking digoxin. Compared to those without, patients on digoxin were older (p=0.007), with a clinical history of HF (p<0.001) and at higher risk of thromboembolic events (p<0.001). No difference in TTR between the two groups was registered (p=0.598). During the follow-up, 85 deaths occurred: 47 CV and 38 non-CV deaths; 35 deaths occurred in digoxin users (20.6%). A significant increased rate of total mortality was observed in digoxin-treated patients (p<0.001). Multivariable analysis showed that digoxin was associated with total mortality (hazard ratio [HR]: 2.224, p<0.001) and CV death (HR: 4.686, p<0.001). A propensity score-matched analysis confirmed that digoxin was associated with total mortality (HR: 2.073, p=0.0263) and CV death (HR: 4.043, p=0.004).. In AF patients on good anticoagulation control with VKAs, digoxin use was associated with a higher rate of total and CV mortality.

Topics: Aged; Anti-Arrhythmia Agents; Anticoagulants; Atrial Fibrillation; Cause of Death; Digoxin; Drug Therapy, Combination; Female; Follow-Up Studies; Heart Failure; Humans; Italy; Male; Propensity Score; Prospective Studies; Risk Assessment; Risk Factors; Stroke; Survival Rate

Digoxin is a widely used drug for ventricular rate control in patients with atrial fibrillation (AF), despite a scarcity of randomised trial data. We studied the use and outcomes of digoxin in patients in the Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET AF).. For this retrospective analysis, we included and classified patients from ROCKET AF on the basis of digoxin use at baseline and during the study. Patients in ROCKET AF were recruited from 45 countries and had AF and risk factors putting them at moderate-to-high risk of stroke, with or without heart failure. We used Cox proportional hazards regression models adjusted for baseline characteristics and drugs to investigate the association of digoxin with all-cause mortality, vascular death, and sudden death. ROCKET AF was registered with ClinicalTrials.gov, number NCT00403767.. In 14,171 randomly assigned patients, digoxin was used at baseline in 5239 (37%). Patients given digoxin were more likely to be female (42% vs 38%) and have a history of heart failure (73% vs 56%), diabetes (43% vs 38%), and persistent AF (88% vs 77%; p<0·0001 for each comparison). After adjustment, digoxin was associated with increased all-cause mortality (5·41 vs 4·30 events per 100 patients-years; hazard ratio 1·17; 95% CI 1·04-1·32; p=0·0093), vascular death (3·55 vs 2·69 per 100 patient-years; 1·19; 1·03-1·39, p=0·0201), and sudden death (1·68 vs 1·12 events per 100 patient-years; 1·36; 1·08-1·70, p=0·0076).. Digoxin treatment was associated with a significant increase in all-cause mortality, vascular death, and sudden death in patients with AF. This association was independent of other measured prognostic factors, and although residual confounding could account for these results, these data show the possibility of digoxin having these effects. A randomised trial of digoxin in treatment of AF patients with and without heart failure is needed.. Janssen Research & Development and Bayer HealthCare AG.

Topics: Aged; Anti-Arrhythmia Agents; Anticoagulants; Atrial Fibrillation; Death, Sudden; Diabetes Mellitus; Digoxin; Factor Xa Inhibitors; Female; Heart Failure; Heart Rate; Humans; Intracranial Embolism; Male; Morpholines; Proportional Hazards Models; Randomized Controlled Trials as Topic; Retrospective Studies; Rivaroxaban; Sex Distribution; Stroke; Thiophenes; Vitamin K; Warfarin

Topics: Anticoagulants; Atrial Fibrillation; Digoxin; Female; Heart Failure; Humans; Male; Risk Assessment; Stroke

Topics: Anticoagulants; Atrial Fibrillation; Digoxin; Female; Heart Failure; Humans; Male; Risk Assessment; Stroke

Atrial fibrillation (AF), the most common sustained arrhythmia requiring treatment worldwide, is one of the major causes of ischemic stroke. Although amiodarone is commonly used for rhythm control in AF, its relationship with stroke has rarely been addressed.We evaluated 16,091 patients who were diagnosed with AF (Classification of Diseases, 9th Revision, Clinical Modification [ICD-9-CM] 427.31 and 427.32) between 1998 and 2011; the date of AF diagnosis was set as the index date. Patients with a history of stroke (ICD-9-CM 430-438) who received amiodarone before the index date or during the following 30 days, or who experienced stroke within 30 days of receiving amiodarone were excluded. Finally, 7548 patients with AF were included in this study and divided into 2 groups according to whether they received amiodarone (Anatomical Therapeutic Chemical code C01BD01) during the study period.The risk of ischemic stroke in AF patients receiving amiodarone was 1.81-fold (95% confidence interval [CI] 1.52-2.16), 1.79-fold (95% CI 1.50-2.14), and 1.78-fold (95% CI 1.49-2.13) higher than in those who did not receive amiodarone, according to crude, Model 1, and Model 2 Cox proportional hazard regression models, respectively. In a demographically stratified analysis, the risk of ischemic stroke was significantly higher in patients aged <65 years, with no comorbidities, who were also taking digoxin or had a low CHA2DS2VASc score.Amiodarone treatment is associated with an increased risk of stroke in patients with AF, especially in those who have an initial low risk of stroke. Antiplatelet drugs and warfarin could reduce the stroke risk in AF patients receiving amiodarone. However, as the combination of digoxin and amiodarone increases the risk of stroke in these patients, the combination of these 2 drugs should be avoided.

Topics: Age Factors; Aged; Amiodarone; Anti-Arrhythmia Agents; Anticoagulants; Atrial Fibrillation; Comorbidity; Digoxin; Drug Therapy, Combination; Female; Humans; Male; Middle Aged; Proportional Hazards Models; Risk Factors; Stroke; Taiwan; Warfarin

Topics: Anti-Arrhythmia Agents; Atrial Fibrillation; Brain Ischemia; Digoxin; Humans; Stroke

Digoxin and related cardiac glycosides have been used for almost 100 years in atrial fibrillation (AF). However, 2 recent analyses of the Atrial Fibrillation Follow-Up Investigation of Rhythm Management (AFFIRM) trial showed inconsistent results regarding the risk of mortality associated with digoxin use. The goal of the present study was to investigate the relationship between digoxin and the risk of ischemic stroke and mortality in Asians.. This study used the National Health Insurance Research Database (NHIRD) in Taiwan. A total of 4781 patients with AF who did not receive any antithrombotic therapy were selected as the study population. Among the study population, 829 participants (17.3%) received the digoxin treatment. The risk of ischemic stroke and mortality in patients who received digoxin and those who did not was compared.. The use of digoxin was associated with an increased risk of clinical events, with an adjusted hazard ratio of 1.41 (95% confidence interval [CI], 1.17-1.70) for ischemic stroke and 1.21 (95% CI, 1.01-1.44) for all-cause mortality. In the subgroup analysis based on coexistence with heart failure or not, digoxin was a risk factor for adverse events in patients without heart failure but not in those with heart failure (interaction P < 0.001 for either end point). Among patients with AF without heart failure, the use of β-blockers was associated with better survival, with an adjusted hazard ratio of 0.48 (95% CI, 0.34-0.68).. Digoxin should be avoided for patients with AF without heart failure because it was associated with an increased risk of clinical events. β-Blockers may be a better choice for controlling ventricular rate in these patients.

Topics: Anti-Arrhythmia Agents; Atrial Fibrillation; Brain Ischemia; Cohort Studies; Digoxin; Humans; Risk Factors; Stroke

The authors report about a patient who was admitted after developing nausea, vomiting, change in vision and lethargy. She was on digoxin 250 mcg once daily among all her other medications in the wake of a recent stroke that was accompanied by atrial fibrillation (AF). Her digitalis levels shortly before and on admission were 3.4 and 2.9 ng/ml, respectively. Her admission rhythm was slowly conducted AF at an average of 35 bpm. After a careful assessment by the cardiology consultant in charge, she received Digibind infusion for a chronic digitalis toxicity with the digoxin immune Fab dose based on the formula recommended in the product literature.(3) A few days observation on the ward ensured that her resting heart rate rose to 65 bpm and that she did not need a pacemaker for a slow AF. Her functional status remained reasonably good as she enjoyed a satisfactory recovery postthrombolysis for her recent stroke.

Topics: Aged; Anti-Arrhythmia Agents; Atrial Fibrillation; Cardiotonic Agents; Digitalis Glycosides; Digoxin; Female; Heart Rate; Humans; Immunoglobulin Fab Fragments; Stroke

We assessed, in patients with a first hospitalization for heart failure (HF), the temporal relationship of the incidence of cardiovascular events, all-cause mortality, and cardiovascular drug treatment.. Data were obtained from the PHARMO Record Linkage System, a population-based registry of pharmacy records linked with hospital discharge records in The Netherlands. Patients were selected based on a first hospital discharge diagnosis of documented HF. Two time-periods were compared: 1998-2002 and 2003-07. In each time-period, we analysed all prescribed cardiovascular medications, all-cause mortality, and cardiovascular events (rehospitalization for HF and ischaemic events) within the first year after hospitalization, and the occurrence of ischaemic events separately (myocardial infarction and ischaemic stroke). Cox-regression analysis was performed to calculate hazard ratios (HR) with 95% confidence intervals (CI). We identified 8276 patients in 1998-2002 and 9548 patients from 2003-07. There was an increase in almost all cardiovascular medication prescriptions in the second period: in particular, beta-blocker prescriptions rose from 36% in 1998-2002 to 55% in 2003-07. In the first year after hospitalization, there was no difference in all-cause mortality or any cardiovascular event (HR 1.00, 95%CI: 0.95-1.05), as a composite endpoint or when analysed separately. The incidence of ischaemic events decreased from 2.7 to 1.9% in the first and second time-period, respectively (HR 0.74, 95%CI: 0.61-0.90).. Prescription of cardiovascular medications in patients with a first hospitalization for HF has increased in recent years, particularly for beta-blockers, and the incidence of ischaemic events may have decreased. There was no decrease in all-cause mortality or cardiovascular events.

Topics: Adrenergic beta-Antagonists; Aged; Aged, 80 and over; Angina Pectoris; Angiotensin-Converting Enzyme Inhibitors; Cardiotonic Agents; Digoxin; Diuretics; Female; Heart Failure; Hospitalization; Humans; Male; Myocardial Infarction; Myocardial Ischemia; Practice Patterns, Physicians'; Prognosis; Spironolactone; Stroke

The prevalence of stroke is increased in individuals with heart failure (HF). The stroke mechanism in HF may be cardiogenic embolism or cerebral hypoperfusion. Stroke risk increases with decreasing ejection fraction and low cardiac output is associated with hypotension and poor survival. We examine the relationship among blood pressure level, history of stroke/transient ischemic attack (TIA), and HF.. We compared the prevalence of self-reported history of stroke or TIA in the REasons for Geographic And Racial Differences in Stroke (REGARDS) participants with HF (as defined by current digoxin use) and without HF. We excluded participants with atrial fibrillation or missing data. We examined the relationship between HF and history of stroke/TIA within tertiles of systolic blood pressure (SBP) adjusting for patient demographic and health characteristics.. Prevalent stroke/TIA were reported by 66 (26.3%) of 251 participants with and 1805 (8.5%) of 21 202 participants without HF (P<0.0001). Within each tertile of SBP, the unadjusted OR (95% CI) for prior stroke/TIA among those with HF compared with those without HF (the reference group) was, 4.0 (2.8 to 5.8) for SBP <119.5 mm Hg, 2.7 (1.8 to 3.9) for SBP >or=119.5 but <131.5 mm Hg, and 2.3 (1.6 to 3.2) for SBP >or=131.5 mm Hg. After adjustment, the relationship between prior stroke/TIA and HF remained significant only within the lowest tertile of SBP (<119.5 mm Hg; 3.0; 1.5 to 6.1).. The odds of prevalent self-reported stroke/TIA are increased in participants with HF and most markedly increased in participants with low SBP. Longitudinal data are needed to determine whether this reflects stroke/TIA secondary to thromboembolism from poor cardiac function or secondary to cerebral hypoperfusion.

Topics: Aged; Aged, 80 and over; Biomarkers; Black People; Blood Pressure; Cohort Studies; Comorbidity; Digoxin; Female; Geography; Heart Failure; Humans; Hypotension; Ischemic Attack, Transient; Male; Medical History Taking; Middle Aged; Odds Ratio; Prevalence; Racial Groups; Risk Factors; Stroke; Surveys and Questionnaires; White People

Topics: Anti-Arrhythmia Agents; Atrial Fibrillation; Blood Platelets; Digoxin; Endothelial Cells; Humans; Stroke; Thrombosis