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 ◽  
...  

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

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
M Thind ◽  
H J Crijns ◽  
G V Naccarelli ◽  
J A Reiffel ◽  
V Corp Dit Genti ◽  
...  

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


2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
M Vamos ◽  
H Calkins ◽  
P R Kowey ◽  
C T Torp-Pederson ◽  
V Corp Dit Genti ◽  
...  

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


2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
M Martinez-Selles ◽  
R Elosua ◽  
M Ibarrola ◽  
M De Andres ◽  
P Diez-Villanueva ◽  
...  

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


2016 ◽  
Vol 72 (1) ◽  
Author(s):  
Alberto Genovesi Ebert ◽  
Furio Colivicchi ◽  
Marco Malvezzi Caracciolo ◽  
Carmine Riccio

The prevention of symptomatic heart failure represents the treatment of patients in the A and B stages of AHA/ACC heart failure classification. Stage A refers to patients without structural heart disease but at risk to develop chronic heart failure. The major risk factors in stage A are hypertension, diabetes, atherosclerosis, family history of coronary artery disease and history of cardiotoxic drug use. In this stage, blockers hypertension is the primary area in which beta blockers may be useful. Beta blockers seem not to be superior to other medication in reducing the development of heart failure due to hypertension. Stage B heart failure refers to structural heart disease but without symptoms of heart failure. This includes patients with asymptomatic valvular disease, asymptomatic left ventricular (LV) dysfunction, previous myocardial infarction with or without LV dysfunction. In asymptomatic valvular disease no data are available on the efficacy of beta blockers to prevent heart failure. In asymptomatic LV dysfunction only few asymptomatic patients have been enrolled in the trials which tested beta blockers. NYHA I patients were barely 228 in the MDC, MERIT and ANZ trials altogether. The REVERT trial was the only trial focusing on NYHA I patients with LV ejection fraction less than 40%. Metoprolol extended release on top of ACE inhibitors ameliorated LV systolic volume and ejection fraction. A post hoc analysis of the SOLVD Prevention trial demonstrated that beta blockers reduced death and development of heart failure. Similar results were reported in post MI patients in a post hoc analysis of the SAVE trial (Asymptomatic LV failure post myocardial infarction). In the CAPRICORN trial about 65% of the patients were not taking diuretics and then could be considered asymptomatic. The study revealed a reduction in mortality and a non-significant trend toward reduction of death and hospital admission for heart failure. Conclusions: beta blockers are not specifically indicated in stage A heart failure. On the contrary, in most of the stage B patients, and particularly after MI, beta blockers are indicated to reduce mortality and, probably, also the progression toward symptomatic heart failure.


EP Europace ◽  
1999 ◽  
Vol 1 (1) ◽  
pp. 35-39 ◽  
Author(s):  
L. Gianfranchi ◽  
M. Brignole ◽  
C. Menozzi ◽  
G. Lolli ◽  
N. Bottoni

Abstract We evaluated the rate of progression of permanent atrial fibrillation (AF) and identified clinical factors that predict this event in 63 consecutive patients who had undergone AV junctional ablation and DDDR pacemaker implantation for drug-refractory paroxysmal atrial fibrillation/flutter. Immediately after ablation, anti-arrhythmic drugs were discontinued in all cases. Permanent AF was con-sidered to have developed if AF was present on two consecutive 6-monthly examinations with no interim documented sinus rhythm. During a mean follow-up of 23±16 months, 22 (35%) of the 63 patients developed permanent AF. The actuarial estimate of progression of permanent AF was 22%, 40% and 56%, respectively, 1, 2 and 3 years after ablation. Age and underlying heart disease were independent predictors of progression of permanent AF. Only one (6%) of 16 patients with idiopathic AF had permanent AF (low risk group). Among the 47 patients with structural heart disease, permanent AF developed in 18 (62%) of the 29 who were aged >75 years or had >12 arrhythmic episodes per year and a symptom duration >4 years (high risk group), but only in three (17%) of the remaining 18 patients who did not (intermediate risk group). In conclusion, during a 3-year follow-up period, about half of the patients with a history of drug-refractory paroxysmal AF did not develop permanent AF after AV junctional ablation and dual-chamber pacemaker implantation, even in the absence of anti-arrhythmic drug therapy. Moreover, subgroups of patients whose risk of permanent AF progression differed were identified on the basis of simple baseline clinical variables. The results of this study form the necessary background for the correct management of patients after AV junction ablation and for the planning of future trials in this field.


2019 ◽  
Vol 109 (3) ◽  
pp. 331-338 ◽  
Author(s):  
Bernadet T. Santema ◽  
Michelle M. Y. Chan ◽  
Jasper Tromp ◽  
Martin Dokter ◽  
Haye H. van der Wal ◽  
...  

Abstract Background In heart failure (HF), levels of NT-proBNP are influenced by the presence of concomitant atrial fibrillation (AF), making it difficult to distinguish between HF versus AF in patients with raised NT-proBNP. It is unknown whether levels of GDF-15 are also influenced by AF in patients with HF. In this study we compared the plasma levels of NT-proBNP versus GDF-15 in patients with HF in AF versus sinus rhythm (SR). Methods In a post hoc analysis of the index cohort of BIOSTAT-CHF (n = 2516), we studied patients with HF categorized into three groups: (1) AF at baseline (n = 733), (2) SR at baseline with a history of AF (n = 183), and (3) SR at baseline and no history of AF (n = 1025). The findings were validated in the validation cohort of BIOSTAT-CHF (n = 1738). Results Plasma NT-proBNP levels of patients who had AF at baseline were higher than those of patients in SR (both with and without a history of AF), even after multivariable adjustment (3417 [25th–75th percentile 1897–6486] versus 1788 [682–3870], adjusted p < 0.001, versus 2231 pg/mL [902–5270], adjusted p < 0.001). In contrast, after adjusting for clinical confounders, the levels of GDF-15 were comparable between the three groups (3179 [2062–5253] versus 2545 [1686–4337], adjusted p = 0.36, versus 2294 [1471–3855] pg/mL, adjusted p = 0.08). Similar patterns of both NT-proBNP and GDF-15 were found in the validation cohort. Conclusion These data show that in patients with HF, NT-proBNP is significantly influenced by underlying AF at time of measurement and not by previous episodes of AF, whereas the levels of GDF-15 are not influenced by the presence of AF. Therefore, GDF-15 might have additive value combined with NT-proBNP in the assessment of patients with HF and concomitant AF. Graphic abstract


Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Peter Leong-Sit ◽  
Karin H Humphries ◽  
May Lee ◽  
George J Klein ◽  
Robert Sheldon ◽  
...  

Background: The natural history of lone atrial fibrillation (AF) is unclear with conflicting data in the literature. We aimed to better describe the clinical outcomes and echocardiographic changes associated with lone AF. Methods: The Canadian Registry of Atrial Fibrillation (CARAF) enrolled 803 non-surgical and non-flutter patients with new onset AF between 1990 and 1996. At enrollment, patients were classified as lone AF (LAF) or not lone AF (Not LAF) based on structural heart disease or hyperthyroidism. Clinical data was prospectively collected with follow-up at 3 months, 1 year, then annually; echocardiograms were performed at enrollment and years 2, 4, and 7. Results: The LAF group (n=212) had a median age of 57 (1 st quartile 44, 3 rd quartile 67) while the Not LAF group (n=591) had a median age of 67 (59, 73), p<0.0001. During the median follow-up of 8 years in the LAF group and 7 years in the Not LAF group, there was a significant difference in survival free from stroke or embolism favoring the LAF group (Figure ). At 8 years, the probability of remaining free of chronic AF was 78.8% vs 69.3% (p=0.02) and free of symptomatic or documented recurrence of AF was 40.1% vs 26.9% (p<0.01) in the LAF vs Not LAF group. The LAF group had smaller LV diastolic and systolic dimensions by 5.5% and 10.2%, respectively, vs the Not LAF group (p<0.0001). The LV mass was smaller at baseline by 21.1% (p<0.0001) vs the Not LAF group, but increased at a greater rate (4.0% vs 0.9%/2 years, p<0.0001). Conclusions: Lone AF, compared to non-lone AF, is associated with a lower rate of death, stroke or embolism, recurrence and progression to chronic AF. Interestingly, LV mass increased significantly only in the Lone AF group.


ESC CardioMed ◽  
2018 ◽  
pp. 2229-2232
Author(s):  
Bernadette Biondi

Atrial fibrillation develops in about 10–25% of patients with hyperthyroidism with a higher risk in patients with toxic multinodular goitre compared to those with Graves disease. Advanced age, history of cardiac failure, and presence of associated cardiovascular risk factors represent independent predictors for the development of atrial fibrillation. Spontaneous reversion to sinus rhythm frequently occurs in successfully treated hyperthyroid patients under 50 years of age with newly diagnosed atrial fibrillation, without underlying heart disease and lower systolic blood pressure. In contrast, atrial fibrillation persisting for 4 months or more after the control of hyperthyroidism rarely reverts to sinus rhythm in mainly elderly patients and in those with heart disease.


2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Athanasios Samaras ◽  
Eleni Vrana ◽  
Anastasios Kartas ◽  
Dimitrios V. Moysidis ◽  
Andreas S. Papazoglou ◽  
...  

Abstract Background Valvular heart disease (VHD) in non-valvular atrial fibrillation (AF) is a puzzling clinical entity. The aim of this study was to evaluate the prognostic effect of significant VHD (sVHD) among patients with non-valvular AF. Methods This is a post-hoc analysis of the MISOAC-AF trial (NCT02941978). Consecutive inpatients with non-valvular AF who underwent echocardiography were included. sVHD was defined as the presence of at least moderate aortic stenosis (AS) or aortic/mitral/tricuspid regurgitation (AR/MR/TR). Cox regression analyses with covariate adjustments were used for outcome prediction. Results In total, 983 patients with non-valvular AF (median age 76 [14] years) were analyzed over a median follow-up period of 32 [20] months. sVHD was diagnosed in 575 (58.5%) AF patients. sVHD was associated with all-cause mortality (21.6%/yr vs. 6.5%/yr; adjusted HR [aHR] 1.55, 95% confidence interval [CI] 1.17–2.06; p = 0.02), cardiovascular mortality (16%/yr vs. 4%/yr; aHR 1.70, 95% CI 1.09–2.66; p = 0.02) and heart failure-hospitalization (5.8%/yr vs. 1.8%/yr; aHR 2.53, 95% CI 1.35–4.63; p = 0.02). The prognostic effect of sVHD was particularly evident in patients aged < 80 years and in those without history of heart failure (p for interaction < 0.05, in both subgroups). After multivariable adjustment, moderate/severe AS and TR were associated with mortality, while AS and MR with heart failure-hospitalization. Conclusion Among patients with non-valvular AF, sVHD was highly prevalent and beared high prognostic value across a wide spectrum of clinical outcomes, especially in patients aged < 80 years or in the absence of heart failure. Predominantly AS, as well as MR and TR, were associated with worse prognosis.


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