Clinical Trials

In patients with heart failure and atrial fibrillation (AF), several clinical trials have reported improved outcomes, including freedom from AF recurrence, quality of life, and survival, with catheter ablation. This article describes the treatment-related outcomes of the AF patients with heart failure enrolled in the CABANA trial (Catheter Ablation Versus Antiarrhythmic Drug Therapy for Atrial Fibrillation). Read More on PubMed

[Figure: see text]. Read More on PubMed

Atrial fibrillation/atrial flutter (AF/AFL) burden increases with increasing duration of AF/AFL history. Read More on PubMed

Despite improvements in the management of atrial fibrillation, patients with this condition remain at increased risk for cardiovascular complications. It is unclear whether early rhythm-control therapy can reduce this risk. Read More on PubMed

The purpose of this study was to compare the win ratio (WR) with the corresponding hazard ratios (HRs) and 1/HR. Read More on PubMed

The optimal timing of catheter ablation for atrial fibrillation (AF) in reference to the time of diagnosis is unknown. We sought to assess the impact of the duration between first diagnosis of AF and ablation, or diagnosis-to-ablation time (DAT), on AF recurrence following catheter ablation. Read More on PubMed

Efficacy and safety of dronedarone was shown in the ATHENA trial for paroxysmal or persistent atrial fibrillation (AF) patients. Further trials revealed safety concerns in patients with heart failure and permanent AF. This review summarizes insights from recent real-world studies and meta-analyses, including reports on efficacy, with focus on liver safety, mortality risk in patients with paroxysmal/persistent AF, and interactions of dronedarone with direct oral anticoagulants. Reports of rapidly progressing liver failure in dronedarone-prescribed patients in 2011 led to regulatory cautions about potential liver toxicity. Recent real-world evidence suggests dronedarone liver safety profile is similar to other antiarrhythmics and liver toxicity could be equally common with many Class III antiarrhythmics. Dronedarone safety concerns (increased mortality in patients with permanent AF) were raised based on randomized controlled trials (RCT) (ANDROMEDA and PALLAS), but comedication with digoxin may have increased the mortality rates in PALLAS, considering the dronedarone-digoxin pharmacokinetic (PK) interaction. Real-world data on apixaban-dronedarone interactions and edoxaban RCT observations suggest no significant safety risks for these drug combinations. Median trough plasma concentrations of dabigatran 110 mg during concomitant use with dronedarone are at acceptable levels, while PK data on the rivaroxaban-dronedarone interaction are unavailable. In RCTs and real-world studies, dronedarone significantly reduces AF burden and cardiovascular hospitalizations, and demonstrates a low risk for proarrhythmia in patients with paroxysmal or persistent AF. The concerns on liver safety must be balanced against the significant reduction in hospitalizations in patients with non-permanent AF and low risk for proarrhythmias following dronedarone treatment. Read More on PubMed

Background The Atrial Fibrillation Effect on Quality-of-Life (AFEQT) questionnaire has recently been validated to measure the impact of atrial fibrillation on quality of life, but a clinically important difference in AFEQT score has not been well defined. Methods and Results To determine the clinically important difference in overall AFEQT (score range= 0 [worst] to 100 [best]) and selected subscales, we analyzed data in the Outcomes Registry for Better Informed Treatment of Atrial Fibrillation (ORBIT-AF) registry, a United States-based outpatient atrial fibrillation registry. AFEQT was assessed at baseline and 1 year in a subset of 1347 ORBIT-AF patients from 80 US sites participating in ORBIT-AF from June 2010 to August 2011. The mean change method was used to relate changes in 1-year AFEQT scores to clinically important changes in the physician assessment of European Heart Rhythm Association functional status (1 class improvement and separately 1 class deterioration). Clinically important differences and 95% CI corresponding to either a 1 European Heart Rhythm Association class improvement or deterioration were 5.4 (3.6-7.2) and -4.2 (-6.9 to -1.5) AFEQT points, respectively. Similarly, clinically important difference values were seen for a 1 European Heart Rhythm Association class improvement for the AFEQT subscales Activities of Daily Living and Symptoms: 5.1 (2.5-7.6) and 7.1 (5.3-9.0) AFEQT points, respectively. Conclusions Based on the anchor of 1 European Heart Rhythm Association class change, changes in AFEQT score of + or -5 points are clinically important changes in patients' health. Clinical Trial Registration URL: https://clinicaltrials.gov . Unique identifier: NCT01165710. Read More on PubMed

Catheter ablation is more effective than drug therapy in restoring sinus rhythm in patients with atrial fibrillation (AF), but its incremental effect on long-term quality of life (QOL) is uncertain. Read More on PubMed

Atrial fibrillation (AF) affects an estimated 33 million people worldwide, leading to increased mortality and an increased risk of heart failure and stroke. Many AF patient registries exist, but the ability to link and compare data across registries is hindered by differences in the outcome measures collected by each registry and a lack of harmonization. Read More on PubMed

Background Cardiovascular clinical trials have traditionally incorporated separate time-to-first-event analyses for their primary efficacy and safety comparisons, but this framework has a number of limitations, including limited patient-centeredness and a traditional requirement for central adjudication. Days alive and out of the hospital (DAOH) has the potential to provide additional insight. Methods and Results TRILOGY ACS (Targeted Platelet Inhibition to Clarify the Optimal Strategy to Medically Manage Acute Coronary Syndromes) was a randomized, multinational clinical trial that compared the effect of prasugrel versus clopidogrel in patients stabilized after non-ST segment elevation acute coronary syndrome treated without revascularization; the trial had a neutral result. DAOH was calculated for each patient using site-submitted adverse event reporting data. We described patterns of DAOH overall, and among younger adults (<75 years old), older adults (≥75 years old), and frail/prefrail patients over 12 months follow-up and used Poisson regression to compare DAOH for patients randomized to prasugrel versus clopidogrel. Of 9249 patients in the overall trial population, 500 (5.4%) died, and 2504 (27.1%) were hospitalized 4150 times over 12 months' follow-up; the mean±SD DAOH was 317±86. The distribution of DAOH over 12 months was left-skewed, with median DAOH 363 days. Among younger adults, older adults, and frail/prefrail patients, mean DAOH were 323, 293, and 304 days, respectively. There were no differences in DAOH by treatment arm in the overall population (rate ratio, 1.00; 95% CI, 0.99-1.01) or any subgroup. Conclusions These results support the feasibility of determining DAOH, a patient-centered outcome that can potentially overcome many of the disadvantages of the traditional time-to-composite-event framework in the clinical trial setting. Clinical Trial Registration URL: https://www.clinicaltrials.gov. Unique identifier: NCT00699998. Read More on PubMed

Surveys of patients with cardiovascular disease have suggested that "home-time"-being alive and out of any health care institution-is a prioritized outcome. This novel measure has not been studied among patients with heart failure (HF). Read More on PubMed

Patient-reported outcome (PRO) data from clinical trials can provide valuable evidence to inform shared decision making, labeling claims, clinical guidelines, and health policy; however, the PRO content of clinical trial protocols is often suboptimal. The SPIRIT (Standard Protocol Items: Recommendations for Interventional Trials) statement was published in 2013 and aims to improve the completeness of trial protocols by providing evidence-based recommendations for the minimum set of items to be addressed, but it does not provide PRO-specific guidance. Read More on PubMed

Atrial fibrillation (AF) often progresses from paroxysmal or persistent to more sustained forms, but the rate and predictors of AF progression in clinical practice are not well described. Read More on PubMed

Pocock et al. (2012, European Heart Journal 33, 176-182) proposed a win ratio approach to analyzing composite endpoints comprised of outcomes with different clinical priorities. In this article, we establish a statistical framework for this approach. We derive the null hypothesis and propose a closed-form variance estimator for the win ratio statistic in all pairwise matching situation. Our simulation study shows that the proposed variance estimator performs well regardless of the magnitude of treatment effect size and the type of the joint distribution of the outcomes. Read More on PubMed

Contemporary data on temporal trends in incidence and survival after atrial fibrillation are scarce. Read More on PubMed

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. Read More on PubMed

Improving health-related quality of life (HRQoL) is an important treatment goal in the management of patients with atrial fibrillation (AF). Uncertainty exists as to whether patients' HRQoL differ when treated with medical rhythm control or rate control. We compared HRQoL between patients treated with rhythm control or rate control in a large observational registry of patients with recent-onset AF. Read More on PubMed

Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia. It is a cause of stroke, heart failure, and death. Guideline-based treatment can improve outcomes in AF. Unfortunately, adherence to these guidelines is low. Get With The Guidelines is a hospital-based performance initiative, which has been shown to improve adherence over time. Get With The Guidelines-AFIB is a novel quality improvement registry designed to improve adherence to AF guidelines. Read More on PubMed

The purpose of this study was to determine if 6-min walk test data assists in treatment decisions for patients with heart failure. Read More on PubMed

The aim of the study was to examine the temporal readmission pattern, proportion of readmissions attributed to cardiovascular (CV) causes, and the duration and costs associated with readmission in hospitalized patients with atrial fibrillation/flutter (AF/AFL). This retrospective cohort study used medical claims data from the PharMetrics Patient-Centric database (IMS Health, Watertown, MA) between January 2007 and March 2008. The patients hospitalized with a primary diagnosis of AF/AFL and with ≥12 months' continuous medical and prescription coverage before and after the initial AF/AFL hospitalization were identified from this database. The main outcome measures were rehospitalization patterns [all-cause, all CV-related (including AF/AFL), and AF/AFL-related only], which were assessed over the 12-month post-index period, and costs of initial and subsequent AF/AFL-related hospitalizations that were compared. The study included 8035 patients with AF/AFL (mean age 66.1 years; 57.6% males). Rehospitalization was common (37.9% of patients), with the most frequent causes being CV (34.1%) and, specifically, AF/AFL-related (26.8%). The highest proportion of rehospitalizations occurred within 30 days of the initial hospitalization (25%). Readmissions with a primary diagnosis of AF/AFL (n = 1238) were significantly longer (4.0 vs. 3.6 days; P = 0.0229) and more costly (US$8966 vs. US$7080; P < 0.0001) than the index hospitalization. Hospitalized AF/AFL patients experience high rates of CV- and AF/AFL-related readmissions, particularly within the first 30 days. Subsequent AF/AFL-related readmissions incur higher costs than the initial AF/AFL hospitalization. Treatments resulting in reduced readmissions would improve patient outcomes, quality of life and the cost burden associated with AF/AFL. Read More on PubMed

Get With The Guidelines (GWTG)-Stroke is a national stroke registry and quality improvement program. We examined the accuracy and reliability of data entered in GWTG-Stroke. Read More on PubMed

Stroke is the most feared complication of atrial fibrillation (AF). Dronedarone is an antiarrhythmic drug with multichannel-blocking properties. Recently, a post hoc analysis of a large randomized trial has suggested a reduction of stroke risk in patients with paroxysmal or persistent AF receiving dronedarone. Read More on PubMed

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. Read More on PubMed

The impact of individual antiarrhythmic drugs (AADs) on mortality and hospital stay in atrial fibrillation (AF) was evaluated. Read More on PubMed

Atrial fibrillation (AF) has a deleterious impact on health-related quality-of-life (HRQoL), but measuring this outcome is difficult. A comprehensive, validated, disease-specific questionnaire to measure the spectrum of QoL domains affected by AF and its treatment is not available. We developed and validated a 20-item questionnaire, Atrial Fibrillation Effect on QualiTy-of-life (AFEQT), in a 6-center, prospective, observational study. Read More on PubMed

We compared the efficacy and safety of amiodarone and dronedarone in patients with persistent atrial fibrillation (AF). Read More on PubMed

We sought to determine the relationship between atrial fibrillation (AF) ablation efficacy, quality of life (QoL), and AF-specific symptoms at 2 years. Read More on PubMed

The Sudden Cardiac Death in Heart Failure Trial (SCD-HeFT) demonstrated that implantable cardioverter-defibrillator (ICD) therapy reduces all-cause mortality in patients with New York Heart Association class II/III heart failure and a left ventricular ejection fraction < or =35% on optimal medical therapy. Whether ICD therapy reduced sudden death caused by ventricular tachyarrhythmias without affecting heart failure deaths in this population is unknown. Read More on PubMed

We sought to compare the efficacy and safety of dronedarone versus amiodarone for the prevention of recurrent atrial fibrillation (AF). Read More on PubMed

Dronedarone is a new antiarrhythmic drug that is being developed for the treatment of patients with atrial fibrillation. Read More on PubMed

Dronedarone is a new multichannel blocker for atrial fibrillation (AF) previously demonstrated to have both rhythm and rate control properties in paroxysmal and persistent AF. The Efficacy and safety of dRonedArone for The cOntrol of ventricular rate during atrial fibrillation (ERATO) trial assessed the efficacy of dronedarone in the control of ventricular rate in patients with permanent AF, when added to standard therapy. Read More on PubMed

It is common practice to restore and maintain sinus rhythm in patients with atrial fibrillation and heart failure. This approach is based in part on data indicating that atrial fibrillation is a predictor of death in patients with heart failure and suggesting that the suppression of atrial fibrillation may favorably affect the outcome. However, the benefits and risks of this approach have not been adequately studied. Read More on PubMed

Dronedarone is a novel antiarrhythmic drug with electrophysiological properties that are similar to those of amiodarone, but it does not contain iodine and thus does not cause iodine-related adverse reactions. Therefore, it may be of value in the treatment of patients with heart failure. Read More on PubMed

The development of atrial fibrillation (AF) in cardiac patients is multifactorial, including not well defined genetic factors. To determine if Asian ethnicity is associated with the development of AF in patients with coronary disease, a meta-analysis was conducted of patient-level data from 7 prospective randomized clinical trials that prospectively collected information on the development of AF: 3 trials in patients with ST-elevation myocardial infarction (Global Use of Strategies to Open Occluded Coronary Arteries [GUSTO] I, GUSTO III, and GUSTO V), 3 trials in patients with non-ST-elevation acute coronary syndromes (Platelet Glycoprotein IIb/IIIa in Unstable Angina: Receptor Suppression Using Integrilin Therapy [PURSUIT], Integrilin to Minimize Platelet Aggregation and Coronary Thrombosis-II [IMPACT II], and Platelet IIb/IIIa Antagonist for the Reduction of Acute Coronary Syndrome Events in a Global Organization Network [PARAGON A]), and 1 trial in patients with both conditions (GUSTO IIb). A total of 94,785 patients were identified (93,050 white, 1,735 Asian). At baseline, Asian patients were younger; had lower body mass indexes; had a lower prevalence of female gender, previous angioplasty, and previous coronary artery bypass grafting; and had a greater prevalence of diabetes compared with white patients. The development of AF was lower in Asian than in white patients (4.7% vs 7.6%, p <0.001), while rates of ventricular tachycardia and fibrillation were similar in the 2 groups. In multivariate logistic regression analysis, Asian ethnicity was associated with significantly lower rates of AF (odds ratio 0.65, 95% confidence interval 0.50 to 0.84, p = 0.001) compared with white ethnicity. In conclusion, similar to previous studies showing a lower incidence of AF in non-Caucasian populations, Asians experiencing acute ischemic syndromes have a significantly lower frequency of AF compared with whites. Further study is needed to investigate the mechanisms and potential genetic underpinnings behind this association. Read More on PubMed

We sought to assess the association of amiodarone use with mortality during consecutive periods in patients with post-acute myocardial infarction with left ventricular systolic dysfunction and/or HF treated with a contemporary medical regimen. Read More on PubMed

Atrial fibrillation (AF) is the most commonly encountered clinical arrhythmia, predominantly affecting elderly patients. There is a continued need for new antiarrhythmic drugs to treat the ever-increasing number of patients with this arrhythmia. Dronedarone is a new antiarrhythmic compound currently being developed for treatment of AF. Read More on PubMed

Amiodarone is effective in maintaining sinus rhythm in atrial fibrillation but is associated with potentially serious toxic effects. Dronedarone is a new antiarrhythmic agent pharmacologically related to amiodarone but developed to reduce the risk of side effects. Read More on PubMed

Limited data exist on trends in incidence of atrial fibrillation (AF). We assessed the community-based trends in AF incidence for 1980 to 2000 and provided prevalence projections to 2050. Read More on PubMed

To summarize safety data such as clinical adverse experiences in clinical trials with a moderate to long-term follow-up, we may use a measurement which accounts for the potential differences in the follow-up duration between treatment groups. The incidence rate, which uses the total person-time follow-up in a treatment group as the denominator, is one of these measures. When treatment comparisons are based on the difference of the incidence rates, it is of interest to construct confidence intervals for the rate differences. In this paper, we first discuss the assumptions and scenarios in which the exposure adjusted incidence rate may be appropriate. Then we review several methods of calculating confidence intervals for the difference of two incidence rates assuming that the number of events come from a Poisson distribution. The methods considered include Wald's method, the two-by-two table method, the Miettinen and Nurminen (MN) method, and the conditional MN method. For all but the MN method, explicit confidence intervals can be obtained. For the MN method, some numerical iterations are required. The properties of these methods are evaluated by simulations. The results show that the MN method outperforms the other three in terms of the coverage of the confidence interval, especially when the rates and therefore the number of events are small. Lastly, data from a clinical study are used to demonstrate the application of the methods. Read More on PubMed

The optimal pharmacologic means to restore and maintain sinus rhythm in patients with atrial fibrillation remains controversial. Read More on PubMed

Summary. A variety of definitions of major bleeding have been used in published clinical studies, and this diversity adds to the difficulty in comparing data between trials and in performing meta-analyses. In the first step towards unified definitions of bleeding complications, the definition of major bleeding in non-surgical patients was discussed at the Control of Anticoagulation Subcommittee of the International Society on Thrombosis and Haemostasis. Arising from that discussion, a definition was developed that should be applicable to studies with all agents that interfere with hemostasis, including anticoagulants, platelet function inhibitors and fibrinolytic drugs. The definition and the text that follows have been reviewed and approved by the cochairs of the subcommittee and the revised version is published here. The intention is to also seek approval of this definition from the regulatory authorities. Read More on PubMed

Atrial fibrillation (AF) is the most common cardiac dysrhythmia and a source of considerable morbidity and mortality, but lifetime risk for AF has not been estimated. Read More on PubMed

This study evaluated the efficacy of antiarrhythmic drugs for the treatment of atrial fibrillation (AF). Read More on PubMed

There are two approaches to the treatment of atrial fibrillation: one is cardioversion and treatment with antiarrhythmic drugs to maintain sinus rhythm, and the other is the use of rate-controlling drugs, allowing atrial fibrillation to persist. In both approaches, the use of anticoagulant drugs is recommended. Read More on PubMed

Maintenance of sinus rhythm is the main therapeutic goal in patients with atrial fibrillation. However, recurrences of atrial fibrillation and side effects of antiarrhythmic drugs offset the benefits of sinus rhythm. We hypothesized that ventricular rate control is not inferior to the maintenance of sinus rhythm for the treatment of atrial fibrillation. Read More on PubMed

Atrial fibrillation is the most common arrhythmia in elderly persons and a potent risk factor for stroke. However, recent prevalence and projected future numbers of persons with atrial fibrillation are not well described. Read More on PubMed

Amiodarone has become an important drug for the treatment of supraventricular and ventricular arrhythmias, in short-term inpatient and outpatient settings. It may also have a role in affecting outcome in patients at high risk for arrhythmic events and sudden death; its place among available therapies is being established in clinical trials. Read More on PubMed

The restoration and maintenance of sinus rhythm is a desirable goal in patients with atrial fibrillation, because the prevention of recurrences can improve cardiac function and relieve symptoms. Uncontrolled studies have suggested that amiodarone in low doses may be more effective and safer than other agents in preventing recurrence, but this agent has not been tested in a large, randomized trial. Read More on PubMed

This study aimed to describe the incidence of atrial fibrillation (AF) among older adults during 3 years of follow-up. Read More on PubMed

Although radiofrequency catheter ablation can be used to effectively treat a variety of arrhythmias, the effects of this procedure on health-related quality of life have not been systematically studied. Read More on PubMed

The prevalence of atrial fibrillation (AF) is related to age. Anticoagulation is highly effective in preventing stroke in patients with AF, but the risk of hemorrhage may be increased in older patients. We reviewed the available epidemiologic data to define the age and sex distribution of people with AF. From four large recent population-based surveys, we estimated the overall age- and gender-specific prevalence of AF. These estimates were applied to the recent US census data to calculate the number of men and women with AF in each age group. There are an estimated 2.2 million people in the United States with AF, with a median age of about 75 years. The prevalence of AF is 2.3% in people older than 40 years and 5.9% in those older than 65 years. Approximately 70% of individuals with AF are between 65 and 85 years of age. The absolute number of men and women with AF is about equal. After age 75 years, about 60% of the people with AF are women. In contrast to people with AF in the general population, patients with AF in recent anticoagulation trials had a mean age of 69 years, and only 20% were older than 75 years. The risks and benefits of antithrombotic therapy in older individuals are important considerations in stroke prevention in AF. Read More on PubMed

Atrial fibrillation (AF) is a common arrhythmia in elderly persons and a common cause of embolic stroke. Most studies of the prevalence and correlates of AF have used selected, hospital-based populations. The Cardiovascular Health Study is a population-based, longitudinal study of risk factors for coronary artery disease and stroke in 5,201 men and women aged > or = 65 years. AF was diagnosed in 4.8% of women and in 6.2% of men at the baseline examination, and prevalence was strongly associated with advanced age in women. Prevalence of AF was 9.1% in men and women with clinical cardiovascular disease, 4.6% in patients with evidence of subclinical but no clinical cardiovascular disease, and only 1.6% in subjects with neither clinical nor subclinical cardiovascular disease. A history of congestive heart failure, valvular heart disease and stroke, echocardiographic evidence of enlarged left atrial dimension, abnormal mitral or aortic valve function, treated systemic hypertension, and advanced age were independently associated with the prevalence of AF. The low prevalence of AF in the absence of clinical and subclinical cardiovascular disease calls into question the existence and clinical usefulness of the concept of so-called "lone atrial fibrillation" in the elderly. Read More on PubMed

To determine the independent risk factors for atrial fibrillation. Read More on PubMed

One hundred forty-two deaths among 743 men ages 50 - 65 years who had been examined and followed 5 - 10 years were investigated and classified on the basis of clinical information from medical and non-medical observers, ECGs and autopsies. A classification based on the condition of the circulation immediately before death appears to be most relevant to studies of sudden death. In 58% of the cases, the subjects collapsed abruptly and his pulse ceased without prior circulatory collapse (arrhythmic death); in 42%, the pulse ceased only after the peripheral circulation had collapsed (deaths in circulatory failure). Thirty-three percent of arrhythmic deaths and 10% of deaths in circulatory failure occurred in a setting of clinical evidence of acute ischemic heart disease (p less than 0.005). Forty-five percent of arrhythmic deaths were preceded by chronic congestive heart failure without circulatory collapse. Ninety-three percent of final illnesses that lasted less than 1 hour ended in arrhythmic deaths; 74% lasted more than 1 day ended in deaths in circulatory failure (p less than 0.001). Eighty-eight percent of deaths that occurred outside of the hospital were arrhythmic; 71% of deaths that occurred in the hospital were deaths in circulatory failure (p less than 0.001). Ninety percent of deaths in which the primary cause of the final illness was heart disease were arrhythmic; 86% of deaths in which the primary cause was other than heart disease were deaths in circulatory failure (p less than 0.001). Ninety-one percent of deaths precipitated by an acute cardiac event were arrhythmic; 98% precipitated by acute respiratory obstruction, hemorrhage, infection, stroke or other noncardiac events were deaths in circulatory failure (p less than 0.001). Read More on PubMed