P1903Efficacy and safety of dronedarone after recent cardioversion in patients with atrial fibrillation/flutter: a post-hoc analysis of the EURIDIS/ADONIS trials

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
M Thind ◽  
H J Crijns ◽  
G V Naccarelli ◽  
J A Reiffel ◽  
V Corp Dit Genti ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
New York ◽  
Heart Disease ◽  
Adverse Events ◽  
Sinus Rhythm ◽  
Structural Heart Disease ◽  
Hazard Ratio ◽  
Post Hoc ◽  
Rheumatic Heart ◽  
Af Recurrence

Abstract Background Cardioversion is commonly performed prior to antiarrhythmic drug initiation for atrial fibrillation/flutter (AF). There are limited data describing baseline differences in patients requiring cardioversion to maintain sinus rhythm compared to those who do not. Likewise, response to antiarrhythmic drugs, including dronedarone, specifically in patients requiring cardioversion has not been well defined. Purpose To evaluate efficacy and safety of dronedarone versus placebo in patients with non-permanent AF who had cardioversion within 5 days prior to randomization in EURIDIS/ADONIS. Methods To qualify for enrolment in EURIDIS/ADONIS patients were required to be in sinus rhythm for at least 1 hour preceding randomization. Of 1237 patients randomized (2:1 dronedarone to placebo), 364 needed cardioversion for study entry (dronedarone 243, placebo 121). AF recurrence was evaluated by ECG obtained during study visits, scheduled transtelephonic monitoring, or at symptom recurrence. Results Cardioversion patients were more likely to have rheumatic heart disease, valvular heart disease, any structural heart disease, and heart failure. Nonetheless, the median time to 1st AF recurrence was longer for dronedarone versus placebo both in cardioversion patients (50 versus 15 days, hazard ratio 0.76, 95% CI 0.59, 0.97) and no cardioversion patients (150 versus 77 days, hazard ratio 0.76, 95% CI 0.64, 0.90), as was time to 1st symptomatic recurrence (cardioversion: 347 versus 87 days, hazard ratio 0.65, 95% CI 0.49, 0.87; no cardioversion: 288 versus 120 days, hazard ratio 0.74, 95% CI 0.62, 0.90) (Figure 1). There was a trend towards fewer 1st AF hospitalizations within 12 months for dronedarone versus placebo (7.8 versus 12.4%, hazard ratio 0.60, 95% CI 0.31, 1.18 in cardioversion patients; 8.4 versus 10.4%, hazard ratio 0.74, 95% CI 0.47, 1.17 in no cardioversion patients). In cardioversion patients, rates of treatment-emergent adverse events with dronedarone versus placebo were 64 versus 66%, serious treatment-emergent adverse events were 19 versus 26%, permanent discontinuations were 9 versus 6%, and deaths were 0 versus 1%. Conclusions 1) Cardioversion-requiring patients have more baseline structural heart disease and overall shorter time to AF recurrence. 2) Dronedarone effectively delayed 1st AF recurrence versus placebo in patients with or without recent cardioversion. 3) Safety of dronedarone in cardioversion patients was similar to placebo and overall observations from EURIDIS/ADONIS despite baseline differences in comorbidities. Acknowledgement/Funding Sanofi, New York, New York, United States of America

P4784Efficacy and safety of dronedarone by duration of atrial fibrillation history: a post-hoc analysis of the ATHENA trial

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
C Blomstrom-Lundqvist ◽  
N Marrouche ◽  
S Connolly ◽  
V Corp Dit Genti ◽  
M Wieloch ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
New York ◽  
Heart Disease ◽  
Sinus Rhythm ◽  
Structural Heart Disease ◽  
Efficacy And Safety ◽  
History Of ◽  
Summary Relative Risk ◽  
Post Hoc ◽  
Symptom Recurrence

Abstract Background Atrial fibrillation (AF) is known to progress over time and the effectiveness of antiarrhythmic therapy may vary based on the duration of a patient's AF history. Outcomes with dronedarone (DRO) based on duration of AF/atrial flutter (AFL) history have not been previously characterized. Purpose To evaluate the efficacy and safety of DRO by time since first known AF/AFL episode in patients studied in the ATHENA trial. Methods 2859 (61.8%) patients from ATHENA with documented first known AF/AFL episode (of 4628 total patients randomized) were included in the analysis. Among these patients, first AF/AFL episode was reported at <3 months (shorter history), 3 to <24 months (intermediate), and ≥24 months (longer) in 1296 (45.3%), 845 (29.6%) and 718 (25.1%) patients, respectively. AF/AFL recurrence was evaluated in patients in sinus rhythm at baseline by ECG during study visits or symptom recurrence. Results Demographics (age, sex) were similar across all groups. Patients with longer AF/AFL history tended to have higher prevalence of coronary heart disease and structural heart disease; and were more likely to have AF/AFL (by 12-lead ECG) at baseline (30%) compared to 26% and 16% for intermediate and shorter history groups. Patients with a longer AF history likely had a prior ablation for AF/AFL (7%) vs patients with an intermediate (2%) or shorter AF/AFL history (1%), and more likely required cardioversion during the study (24%) vs intermediate (17%) and shorter history groups (11%). Outcomes and efficacy are reported in Table 1. Rates of treatment-emergent adverse events (TEAEs), serious TEAEs, permanent drug discontinuations, and deaths were similar across all AF/AFL groups. Table 1. Outcomes and efficacy summary Relative Risk, dronedarone (DRO) vs placebo (PBO)1 (95% CI)1,2 AF/AFL <3 months AF/AFL 3 to <24 months AF/AFL ≥24 months PBO (n=626) DRO (n=670) PBO (n=429) DRO (n=416) PBO (n=363) DRO (n=355) First CV hospitalization3 or death (any cause) 0.79 (0.65, 0.96) 0.72 (0.56, 0.92) 0.84 (0.66, 1.07) First CV hospitalization 0.78 (0.64, 0.96) 0.70 (0.55, 0.91) 0.82 (0.63, 1.05) Death (any cause) 0.82 (0.54, 1.24) 0.85 (0.43, 1.68) 1.13 (0.61, 2.10) First AF/AFL recurrence4 0.80 (0.65, 0.97) 0.67 (0.53, 0.84) 0.81 (0.65, 1.02) 1Cox regression model. 2On study period, all randomized patients. 3Main reason was AF/other supraventricular rhythm disorders. 4On selected patients in sinus rhythm at baseline (AF/AFL <3 months: PBO n=514, DRO n=529; 3 to <24 months: PBO n=288, DRO n=312; ≥24 months: PBO n=252, DRO n=250). CV = Cardiovascular. Conclusions Nearly half the patients in ATHENA had a shorter history (<3 months) of AF/AFL prior to randomization. Patients with a longer history of AF/AFL had a greater burden of AF/AFL based on baseline rhythm status, ablation history, and cardioversions required post randomization. Despite these differences, clinical outcomes, efficacy, and safety of DRO appeared to be generally consistent irrespective of duration of AF/AFL history. Acknowledgement/Funding Sanofi, New York, New York, United States of America

P1034Impact of ablation status on the efficacy and safety of dronedarone in patients with atrial fibrillation/flutter: a post-hoc analysis of the ATHENA trial

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
M Vamos ◽  
H Calkins ◽  
P R Kowey ◽  
C T Torp-Pederson ◽  
V Corp Dit Genti ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
New York ◽  
Adverse Events ◽  
Antiarrhythmic Drugs ◽  
Hazard Ratio ◽  
Efficacy And Safety ◽  
Post Hoc Analysis ◽  
Post Hoc ◽  
Unites States ◽  
Symptom Recurrence

Abstract Background Despite increasing use of ablation for atrial fibrillation/flutter (AF/AFL), few systematic data exist on the use of dronedarone and other antiarrhythmic drugs after ablation. Purpose To assess efficacy and safety of dronedarone after ablation in patients with paroxysmal/persistent AF/AFL randomized to dronedarone or placebo in the ATHENA trial (NCT00174785). Methods In ATHENA, 196 patients (dronedarone 90, placebo 106) had an ablation for AF/AFL prior to study entry. AF/AFL recurrence was evaluated in patients in sinus rhythm at baseline (dronedarone 63, placebo 65) by ECG during study visits or symptom recurrence. Results Ablated vs non-ablated patients were more likely to be male, have an implantable cardioverter defibrillator or pacemaker implanted, or be receiving an oral anticoagulant. Fewer ablated patients had an AF/AFL recurrence with dronedarone (36 [57%]) than with placebo (46 [71%]). Median time to first AF/AFL recurrence was significantly longer with dronedarone versus placebo (561 versus 180 days; hazard ratio 0.65 [95% CI 0.42–1.00], p<0.05; Fig 1). Time to first cardiovascular hospitalization or death was similar with dronedarone versus placebo (hazard ratio 0.98 [0.62–1.53]). On-treatment rates of treatment-emergent adverse events with dronedarone versus placebo were 83.1 versus 75.5%, serious treatment-emergent adverse events were 27.0 versus 18.9%, permanent drug discontinuations were 10.1 versus 15.1%, and deaths were 0 versus 1.9%. Conclusions Dronedarone delayed AF/AFL recurrence in patients with a prior AF/AFL ablation. Safety outcomes were consistent with the overall ATHENA trial. Adequately sized prospective studies are needed to confirm these observations. Given the sparsity of data for antiarrhythmic drugs after ablation, this retrospective analysis has merit and is useful for hypothesis generation. Acknowledgement/Funding Sanofi, New York, New York, Unites States of America

Advanced interatrial block precedes atrial fibrillation and stroke. The prospective interatrial Block And Yearly EventS (BAYES) registry

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
M Martinez-Selles ◽  
R Elosua ◽  
M Ibarrola ◽  
M De Andres ◽  
P Diez-Villanueva ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Heart Disease ◽  
Sinus Rhythm ◽  
Structural Heart Disease ◽  
P Wave ◽  
Wave Duration ◽  
P Wave Duration ◽  
Previous Diagnosis ◽  
Surface Ecg ◽  
Interatrial Block

Abstract Background Advanced interatrial block (IAB), prolonged and bimodal P waves in surface ECG inferior leads, is an unrecognized surrogate of atrial dysfunction and a trigger of atrial dysrhythmias, mainly atrial fibrillation (AF). Our aim was to prospectively assess whether advanced IAB in sinus rhythm precedes AF and stroke in elderly outpatients with structural heart disease, a group not previously studied. Methods Prospective observational registry that included outpatients aged ≥70 years with structural heart disease and no previous diagnosis of AF. Patients were divided into three groups according to P-wave characteristics. Results Among 556 individuals, 223 had normal P-wave (40.1%), 196 partial IAB (35.3%), and 137 advanced IAB (24.6%). After a median follow-up of 694 days; 93 patients (16.7%) developed AF, 30 stroke (5.4%), and 34 died (6.1%). Advanced IAB was independently associated with AF (hazard ratio [HR] 2.9, 95% confidence interval [CI] 1.7–5.1, p&lt;0.001), stroke (HR 3.8, 95% CI 1.4–10.7, p=0.010), and AF/stroke (HR 2.6, 95% CI 1.5–4.4, p=0.001). P-wave duration (ms) was independently associated with AF (HR 1.05, 95% CI 1.03–1.07, p&lt;0.001), AF/stroke (HR 1.04, 95% CI 1.02–1.06, p&lt;0.001), and mortality (HR 1.04, 95% CI 1.00–1.08, p=0.021). Conclusions The presence of advanced IAB in sinus rhythm is a risk factor for AF and stroke in an elderly population with structural heart disease and no previous diagnosis of AF. P-wave duration was also associated with all-cause mortality. Figure. Age- and sex-adjusted linear and non-linear association between P-wave duration (msec) and atrial fibrillation (A), stroke (B), and atrial fibrillation or stroke (C) risk. Results of a generalized additive model with spline smoothing functions and 4 degrees of freedom. Figure 1. Kaplan-Meyer curves of survival free of atrial fibrillation (A), stroke (B) and atrial fibrillation or stroke (C) in patients with normal P-wave, partial interatrial block (IAB) and advanced IAB. Funding Acknowledgement Type of funding source: None

scholarly journals Increased α-Actinin-2 Expression in the Atrial Myocardium of Patients with Atrial Fibrillation Related to Rheumatic Heart Disease

Cardiology ◽  
2016 ◽  
Vol 135 (3) ◽  
pp. 151-159 ◽  
Author(s):  
Lei Zhang ◽  
Nan Zhang ◽  
Xuejiao Tang ◽  
Fajin Liu ◽  
Suxin Luo ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Heart Disease ◽  
Sinus Rhythm ◽  
Rheumatic Heart Disease ◽  
Collagen Content ◽  
Atrial Fibrosis ◽  
Smad Pathway ◽  
Smad Signaling Pathway ◽  
Tgf Β1 ◽  
Rheumatic Heart

Objectives: Atrial fibrosis, a marker of atrial structural remodeling, plays a critical role in atrial fibrillation (AF). α- Actinin-2 is associated with structural remodeling related to stretching. The transforming growth factor-β1 (TGF-β1)/Smad pathway plays an important role in atrial fibrosis. We investigated the effects of the TGF-β1/Smad signaling pathway on α-actinin-2 in atrial fibrosis in patients with AF. Methods: Forty-one right atrial specimens obtained from patients with rheumatic heart disease (RHD) were divided into a chronic (c)AF group, i.e. RHD + cAF (n = 29), and a sinus rhythm group, i.e. RHD + sinus rhythm (n = 12). Patients with congenital heart disease (CHD) and sinus rhythm who underwent heart surgery served as controls (n = 10). Fibrosis was assessed by histological examination, and expression of α-actinin-2, TGF-β1 and Smad2/phosphorylated Smad2 (p-Smad2) was evaluated by immunohistochemistry, quantitative real-time PCR and Western blotting. In rat atrial fibroblasts treated with TGF-β1, the collagen content was measured using hydroxyproline detection, and α-actinin-2 and p-Smad2 were evaluated by semiquantitative reverse-transcription PCR and Western blotting. Results: The histology results revealed a significant increase in atrial fibrosis in AF patients. The collagen content, mRNA and protein expression levels of α-actinin-2 and the components of the TGF-β1/Smad signaling pathway were significantly gradually increased in the CHD + sinus rhythm, RHD + sinus rhythm and RHD + cAF groups (p < 0.05). The mRNA and protein levels of α-actinin-2 and TGF-β1 in RHD patients were positively correlated with the collagen volume fraction. A positive correlation between the expression of α-actinin-2 and TGF-β1 was also observed. In rat atrial fibroblasts treated with TGF-β1, the collagen content was greater than that in the control group (p < 0.05), and the expression levels of α- actinin-2 and p-Smad2 were also upregulated (p < 0.05). Conclusions: α-Actinin-2 expression was increased in the atrial tissues of patients with AF secondary to RHD. α-Actinin-2 was upregulated via the TGF-β1/Smad pathway in atrial fibroblasts, which suggests that it may be involved in TGF-β1/Smad pathway-induced atrial fibrosis in patients with AF.

Galectin-3 Induces Atrial Fibrosis by Activating the TGF-β1/Smad Pathway in Patients with Atrial Fibrillation

Cardiology ◽  
2020 ◽  
Vol 145 (7) ◽  
pp. 446-455 ◽  
Author(s):  
Minghan Xiao ◽  
Meixia Zhang ◽  
Mengjun Bie ◽  
Xiaowen Wang ◽  
Jingwen Guo ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Heart Disease ◽  
Sinus Rhythm ◽  
Rheumatic Heart Disease ◽  
Atrial Fibrosis ◽  
Smad Pathway ◽  
Galectin 3 ◽  
The Relationship ◽  
Tgf Β1 ◽  
Rheumatic Heart

Background: Atrial fibrosis plays a critical role in the occurrence and maintenance of atrial fibrillation. The role of TGF-β1 in mediating atrial fibrosis is well documented. The β-galactoside-binding lectin galectin-3 (Gal-3) is mainly produced by macrophages in biological events such as inflammation and angiogenesis. Previous studies have shown that Gal-3 is associated with atrial fibrosis, but the relationship between TGF-β1 and Gal-3 in atrial fibrosis remains unclear. Objective: To determine whether Gal-3 induces atrial fibrosis and atrial fibrillation by activating the TGF-β1/Smad pathway and whether the expression of Gal-3 is mediated by TGF-β1, which can enable assessing the relationship between Gal-3 and TGF-β1 in atrial fibrosis. Methods: In this study, 30 patients’ right atrial appendages were collected and divided into 3 groups: congenital heart disease sinus rhythm group (n = 10, as a control group), rheumatic heart disease sinus rhythm group (n = 10), and rheumatic heart disease atrial fibrillation group (n = 10). Rat atrial fibroblasts were cultured in vitro, and recombinant Gal-3 and recombinant TGF-β1 proteins were added to the cell culture. The expression of Gal-3, TGF-β1, Smad2, and collagen I was detected by Western blotting and quantitative real-time PCR. Atrial tissues were stained with Masson’s trichrome stain to evaluate the extent of atrial fibrosis. The expression of Gal-3 and TGF-β1 was detected by immunohistochemical staining and immunofluorescence staining. Gal-3 and TGF-β1 interaction was demonstrated by immunoprecipitation. Results: The expression levels of Gal-3, TGF-β1, Smad2, and collagen I were elevated in the rheumatic heart disease atrial fibrillation group compared with the congenital heart disease sinus rhythm group and the rheumatic heart disease sinus rhythm group. In cultured atrial fibroblasts, there is a synergistic interaction between Gal-3 and TGF-β1. Gal-3 stimulated the TGF-β1/Smad pathway, and overexpression of TGF-β1 induced Gal-3 expression. Conclusions: Gal-3 and TGF-β1 interact with each other and stimulate the downstream TGF-β1/Smad pathway. This finding suggests that Gal-3 could be an important factor in TGF-β1-induced fibrosis in atrial fibrillation.

scholarly journals Amiodarone in the treatment of atrial fibrillation of patients with rheumatic heart disease after valve replacement

2019 ◽  
Vol 35 (4) ◽  
Author(s):  
Kebiao Chen ◽  
Li Qin ◽  
Xin Lu ◽  
Tao Xia ◽  
Qing Gu
Keyword(s):  
Atrial Fibrillation ◽  
Heart Disease ◽  
Sinus Rhythm ◽  
Rheumatic Heart Disease ◽  
Valve Replacement ◽  
Control Group ◽  
Observation Group ◽  
Maintenance Rate ◽  
Monitoring Time ◽  
Rheumatic Heart

Objectives: To explore the efficacy of amiodarone in the treatment of atrial fibrillation for patients with rheumatic heart disease after valve replacement. Methods: Eighty-six patients with rheumatic heart disease who were hospitalized between June 2016 and June 2017 and developed atrial fibrillation after valvular heart valve replacement were randomly divided into a control group and an observation group, 42 cases in each group. The control group was treated with routine medical treatment, while the observation group was given amiodarone on the basis of routine treatment. The cardiac function of the two groups were observed and recorded. Postoperative atrial fibrillation conversion rate, sinus rhythm maintenance rate, intensive care unit (ICU) monitoring time and hospital stay were compared between the two groups. Results: Compared with the control group, the improvement of cardiac function indexes of the observation group was better, and the difference was statistically significant (P<0.05). The atrial fibrillation conversion rate and the maintenance rate of sinus rhythm of the observation group were 76.2% and 47.6% respectively, which were significantly higher than 57.1% and 33.3% of the control group; the differences had statistical significance (P<0.05). The ICU monitoring time and hospitalization time of the patients in the observation group were (1.69±0.91) d and (10.24±1.11) d respectively, which were significantly shorter than (2.83±0.95) d and (14.07±1.17) d in the control group (P<0.05); the differences were statistically significant (P<0.05). Conclusion: Amiodarone can effectively treat valve replacement associated atrial fibrillation of patients with rheumatic heart disease. It can significantly improve the heart function, prevent the recurrence of atrial fibrillation, maintain sinus rhythm after operation, and shorten the time of ICU monitoring and hospitalization. doi: https://doi.org/10.12669/pjms.35.4.1298 How to cite this:Chen K, Qin L, Lu X, Xia T, Gu Q. Amiodarone in the treatment of atrial fibrillation of patients with rheumatic heart disease after valve replacement. Pak J Med Sci. 2019;35(4):---------. doi: https://doi.org/10.12669/pjms.35.4.1298 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Comparison of dronedarone vs. flecainide in the maintenance of sinus rhythm, following electrocardioversion in adults with persistent atrial fibrillation: a systematic review and meta-analysis

2020 ◽  
Author(s):  
Hannah Wilson ◽  
Declan Patton ◽  
Zena Moore ◽  
Tom O’Connor ◽  
Linda Nugent
Keyword(s):  
Atrial Fibrillation ◽  
Sinus Rhythm ◽  
Meta Analysis ◽  
Significant Risk ◽  
Structural Heart Disease ◽  
Persistent Atrial Fibrillation ◽  
Similar Efficacy ◽  
Future Research ◽  
Reduced Risk ◽  
Af Recurrence

Abstract Aims To compare flecainide and dronedarone for sinus rhythm (SR) maintenance following electrocardioversion of persistent atrial fibrillation (AF), in patients with minimal or no structural heart disease. Methods and results A systematic search of publications using EMBASE, CENTRAL, CINAHL, and MEDLINE (1989–2019), identified a total of 595 articles. No limitations were applied. Nine articles met the inclusion criteria [five randomized controlled trials (RCTs) and four cohort studies], encompassing 1349 persistent AF candidates. Two retrospective studies compared flecainide with dronedarone, indicating a 6% reduced risk of AF recurrence with flecainide; however, results were not statistically significant [risk ratio (RR) 0.94, 95% confidence interval (CI) 0.71–1.24; P = 0.66]. One RCT compared dronedarone to placebo, demonstrating a 28% reduced risk of AF recurrence at 6 months (RR 0.72, 95% CI 0.58–0.90; P = 0.004). Two RCTs compare flecainide to placebo, when a 16% decreased risk of AF recurrence at 6–12 months was indicated; however, these results were not statistically significant (RR 0.84, 95% CI 0.66–1.07; P = 0.16). Within a 6- to 12-month follow-up period, a combined recurrence rate of AF was examined, in which flecainide and dronedarone maintained SR in 50% and 42%, respectively. Four articles satisfied quality appraisal, one of which focused on flecainide data. Conclusion Dronedarone and flecainide displayed similar efficacy in maintaining SR in patients following electrocardioversion for persistent AF. The SR maintenance was numerically but not statistically significant in the flecainide group. Side effects uncovered similar pro-arrhythmic activity. However, in light of the deficiency of volume and quality of available evidence, the writer acknowledges the requirement for future research.

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