Dronedarone In Patients Research Articles

Abstract 15002: Real-World Healthcare Resource Utilization Among US Patients With Atrial Fibrillation Receiving Dronedarone versus Ablation as 1st-Line Therapy

Introduction: Catheter ablation is used increasingly as a 1st-line (1L) alternative to antiarrhythmic drugs (AAD) including dronedarone in patients with atrial fibrillation (AF). Healthcare resource utilization (HCRU)-related costs with dronedarone vs 1L ablation are unknown. Methods: We conducted a retrospective, observational cohort study using Optum Clinformatics Data Mart® from Jan 2012-Jan 2022 among US adults with AF and no prior rhythm control therapy who received new AAD therapy with dronedarone (index: date of incident dronedarone fill) vs those who received 1L ablation, or a non-dronedarone AAD followed by ablation within 3 mo (index: date of first recorded ablation or AAD). Patients were required to have ≥24 mo of pre-index data, and ≥3 mo follow-up. Patients in the 1L ablation cohort were propensity score matched 2:1 to the dronedarone cohort. Mean payer costs per patient per month (PPPM) during the 24-mo post-index period were calculated for total HCRU, inpatient visits, emergency room (ER) visits, outpatient physicians’ office visits, and all outpatient visits, and compared by zero-inflated negative binomial (ZINB) regression model. Results: Post-matching, the dronedarone (n=1440) and 1L ablation (n=2253) cohorts had similar baseline characteristics (mean age at index: 68.4 vs 67.7 years; male: 57.7% vs 59.3%; mean time from AF diagnosis to index: 80.2 vs 91.6 days; Charlson comorbidity index: 2.3 vs 2.2; CHADS2-VASc score: 3.4 vs 3.2). Mean PPPM costs were lower with dronedarone vs 1L ablation for all-cause total HCRU, inpatient visits, any outpatient visit, ER visit, and outpatient office visit (Table). ZINB analyses showed significant cost differences for all-cause total HCRU and any outpatient visit events. Conclusion: In patients with AF and no prior rhythm control therapy, 1L dronedarone was associated with lower total HCRU and outpatient visit costs during 24-mo follow-up vs 1L ablation; future studies will assess cost-effectiveness.

The impact of dronedarone on patients with atrial fibrillation and diabetes – a sub-analysis of the ATHENA and EURIDIS/ADONIS trials

Abstract Background Diabetes is a well-established risk factor for the development of atrial fibrillation (AF), and is associated with worse outcomes. Both the ATHENA (NCT00174785) and EURIDIS (NCT00259428)/ADONIS (NCT00259376) were randomized, double-blind, placebo-controlled clinical trials, that evaluated dronedarone 400 mg BID vs placebo (2:1 ratio) in patients with AF and atrial flutter (AFL). The aim of this post-hoc analysis was to evaluate the efficacy and safety of dronedarone in patients with or without diabetes. Methods Patients from the ATHENA trial with diabetes, and from the EURIDIS/ADONIS trials with diabetes, >1 elevated glucose level during trial (unfasted ≥11; fasted ≥7 mmol/L) or presence of diabetes medications were identified and categorized according to diabetes status at baseline. Descriptive analyses of baseline characteristics in patients with and without diabetes receiving dronedarone or placebo were assessed, and time to occurrence of the primary outcomes, CV hospitalization or death in ATHENA and AF/AFL recurrence within 12 months in EURIDIS/ADONIS, were estimated using the Kaplan–Meier method. Log-rank test was used to assess the statistical differences of the survival curves. Results A total of 945 (20.4%; dronedarone [N=482], placebo [N=463]) patients of 4628 patients in ATHENA, and 215 (17.4%; dronedarone [N=148], placebo [N=67]) of 1237 patients in EURIDIS/ADONIS had type 2 diabetes. Patients with diabetes were more likely to have coronary heart disease, hypertension, or structural heart disease in both trials. In ATHENA, there were higher rates of CV hospitalization or death in patients with diabetes (39.5%) than without (34.7%). The proportion of patients with diabetes with first CV hospitalization or death was lower with dronedarone versus placebo (35.1 vs 44.1%) and the time to first event occurred significantly later with dronedarone than placebo (log-rank p=0.005; Figure 1). In ATHENA, median time to first AF/AFL recurrence occurred significantly later with dronedarone vs placebo consistently in patients with diabetes (722 vs 527 days; log-rank p=0.004) or without diabetes (741 vs 492 days; log-rank p<0.001). In EURIDIS/ADONIS, the median time to first AF/AFL recurrence occurred later with dronedarone versus placebo in both patients with diabetes (100 vs 23 days; log-rank p non-significant) and without (120 vs 59 days; log-rank p<0.001; Figure 2). Occurrence of any treatment-emergent adverse event [TEAE] (ATHENA: 74.9 vs 71.2%; EURIDIS/ADONIS: 77.7 vs 68.1%) and serious TEAEs (ATHENA 23.8 vs 18.9%; EURIDIS/ADONIS 25.7 vs 18.5%) with dronedarone were similar for patients with or without diabetes. Conclusion Diabetic patients had shorter time to AF recurrences and higher rates of CV hospitalization than patients without diabetes. Dronedarone was equally safe, decreasing the risk of CV hospitalization or death, and effective, delaying AF/AFL recurrences, in patients with and without diabetes. Funding Acknowledgement Type of funding sources: Private grant(s) and/or Sponsorship. Main funding source(s): Sanofi

Efficacy and safety of dronedarone vs placebo in patients with atrial fibrillation or atrial flutter across a spectrum of renal function: post hoc analyses of the EURIDIS-ADONIS trials

Abstract Background/Introduction The use of antiarrhythmic drugs in patients with chronic kidney disease (CKD) is complex because impaired renal clearance can cause increased drug levels, and risk of intolerance or adverse events. Since CKD commonly co-occurs with atrial fibrillation/atrial flutter (AF/AFL), it is important to establish efficacy and safety for such drugs when used in AF/AFL patients with CKD. Purpose To evaluate the efficacy and safety of dronedarone in patients with AF or AFL across different levels of renal function. Methods This post hoc analysis evaluated pooled data from two multicentre, double-blind, randomised (2:1) trials of rhythm control with dronedarone 400 mg twice daily vs placebo. Primary endpoint was time to first recurrence of AF or AFL. Renal function (estimated glomerular filtration rate [eGFR]) was assessed with the CKD-Epidemiology Collaboration equation. Patients were grouped by eGFR strata. Log-rank testing and Cox regression were used to compare time to events between treatment groups. Results Most (85%) patients had mild or mild-to-moderate decrease in eGFR (Table 1). Median time to first AF recurrence was significantly longer in the dronedarone vs placebo group for all eGFR subgroups except the 30–44 mL/min group (Figure 1), where the trend was consistent; however, the small population size may have precluded meaningful analyses in this subgroup. Serious adverse events, deaths, and treatment discontinuations did not differ notably between each group irrespective of eGFR strata. Conclusions This analysis confirms the efficacy and safety of dronedarone in patients with AF across a wide spectrum of renal function. Figure 1 Funding Acknowledgement Type of funding source: Private company. Main funding source(s): Sanofi

Dronedarone vs placebo in patients with atrial fibrillation or atrial flutter across a range of renal function: a post hoc analysis of the ATHENA trial

Abstract Background The use of antiarrhythmic drugs in patients with chronic kidney disease (CKD) is challenging due to issues with renal clearance, drug accumulation and increased proarrhythmic risks. Since CKD is a common comorbidity with atrial fibrillation (AF), it is important to establish the efficacy and safety for antiarrhythmic drug treatment in patients with CKD. Purpose To evaluate the efficacy and safety of dronedarone in patients with AF or atrial flutter (AFL) across different stages of renal impairment. Methods In this post-hoc analysis of ATHENA (NCT00174785), a randomised, double-blind trial of dronedarone 400 mg BID vs placebo in patients with AF or AFL plus additional risk factors for death and a calculated glomerular filtration rate ≥10 mL/min, the primary outcome was time to first cardiovascular (CV) hospitalisation or death. Renal function (estimated glomerular filtration rate [eGFR]) was assessed using CKD Epidemiology Collaboration equation and patients were grouped by eGFR (10–44, 45–59, ≥60 mL/min). Log-rank testing and Cox regression were used to compare time to events between treatment groups. Results In ATHENA, 43.6% of placebo and 42.2% of dronedarone patients had mild-to-moderate CKD (Table). Median time to CV hospitalisation/death was longer in all strata for dronedarone vs placebo, reaching significance in the 45–59 and ≥60 mL/min groups (Figure 1). There was a trend towards more treatment-emergent adverse events (TEAEs), deaths and discontinuations due to TEAEs in patients with eGFR 10–44 mL/min. No clear difference in safety was seen between treatment arms except for discontinuations, which were higher with dronedarone. Conclusions This analysis confirms the efficacy of dronedarone, demonstrated in ATHENA, across different stages of renal impairment. Further assessment of safety will require larger populations of patients with CKD. Figure 1 Funding Acknowledgement Type of funding source: Private company. Main funding source(s): Sanofi

Evaluation of the Switch From Amiodarone to Dronedarone in Patients With Atrial Fibrillation: Results of the ARTEMIS AF Studies.

Background:Switching between antiarrhythmic drugs is timed to minimize arrhythmia recurrence and adverse reactions. Dronedarone and amiodarone have similar electrophysiological profiles; however, little is known about the optimal timing of switching, given the long half-life of amiodarone.Methods:The ARTEMIS atrial fibrillation (AF) Loading and Long-term studies evaluated switching patients with paroxysmal/persistent AF from amiodarone to dronedarone. Patients were randomized based on the timing of the switch: immediate, after a 2-week, or after a 4-week washout of amiodarone. Patients who did not convert to sinus rhythm after amiodarone loading underwent electrical cardioversion. The primary objectives were, for the Loading study, to evaluate recurrence of AF ≤60 days; and for the Long-term study, to profile the pharmacokinetics of dronedarone and its metabolite according to different timings of dronedarone initiation.Results:In ARTEMIS AF Loading, 176 were randomized (planned 768) after a 28 ± 2 days load of oral amiodarone. Atrial fibrillation recurrence trended less in the immediate switch versus 4-week washout group (hazard ratio [HR] = 0.65 [97.5% CI: 0.34-1.23]; P = .14) and in the 2-week washout versus the 4-week washout group (HR = 0.75 [97.5% CI: 0.41-1.37]; P = .32). In ARTEMIS AF Long-term, 108 patients were randomized (planned 105). Pharmacokinetic analyses (n = 97) showed no significant differences for dronedarone/SR35021 exposures in the 3 groups.Conclusion:The trial was terminated early due to poor recruitment and so our findings are limited by low numbers. However, immediate switching from amiodarone to dronedarone appeared to be well tolerated and safe.

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

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

Efficacy and safety of dronedarone in patients with amiodarone-induced hyperthyroidism: a clinical study.

The aim of the study was to examine the safety and efficacy of dronedarone in patients with a history of atrial fibrillation and amiodarone-induced hyperthyroidism. We conducted a prospective study to evaluate the use of amiodarone and dronedarone in 124 patients with a history of paroxysmal atrial fibrillation who had no additional structural heart disease. All patients received amiodarone 200 mg qd. Out of 124 patients, 56 (45%) switched to dronedarone 400 mg bid due to amiodarone-induced hyperthyroidism and the remaining 68 patients (55%), with normal thyroid function, continued to receive amiodarone. The follow-up period was 12 months, and the patients were regularly monitored. The primary outcome after 6 months dronedarone and amiodarone group was 56 and 68, including 38 (68%) and 54 (79.4%) (Odds ratio [OR] = 1.17, 95% confidence interval [95% CI] = 0.68-2.02) patients with sinus rhythm (SR) and 18 (32.14%) and 14 (28.6%) (odds ratio [OR] = 0.64, confidence interval [95% CI] = 0.29-1.40) patients with atrial fibrillation (AF). The secondary outcome after 12 months showed significant difference in thyroid function in the dronedarone group. Out of 46 patients, 24 (56.18%) patients reduced hyperthyroidism compared to the amiodarone group; out of 68, 6 (8.9%) patients were observed to have hyperthyroidism. At 12 months, there were 24 (43%) and 22 (62%) (odds ratio [OR] = 0.75, confidence interval [95% CI] = 0.38-1.49) patients with SR, and 32 (57%) and 26 (38%) (odds ratio [OR] = 0.67, confidence interval [95% CI] = 0.36-1.25) patients with AF. In our study, dronedarone appears to be a good therapeutic option in the treatment of atrial fibrillation in patients with amiodarone-induced hyperthyroidism. However, long-term studies are needed to estimate the efficacy and toxicity of both drugs.

Safety of apixaban in combination with dronedarone in patients with atrial fibrillation

BackgroundThere have been concerns about bleeding risks for patients with atrial fibrillation treated with dronedarone in combination with new oral anticoagulants (NOACs). The aim of the study was to compare the bleeding risks with the apixaban + dronedarone and warfarin + dronedarone combinations. MethodRetrospective study of Swedish nationwide health registers. All patients with atrial fibrillation who used dronedarone in combination with apixaban or warfarin during 2013–2016 were identified. Two propensity matched cohorts of each 1681 patients were compared. The main endpoint included intracranial bleeding, bleedings with hospitalization and fatal bleedings. ResultsBleedings thus defined occurred at rates of 1.31 and 2.14 per 100 years at risk with the apixaban and warfarin combinations respectively (p = 0.121). The hazard ratio with the apixaban combination was 0.66 (CI 0.35–1.23) compared to the warfarin combination. No significant differences were seen regarding secondary endpoints. ConclusionMajor bleedings were rare among patients with atrial fibrillation treated with dronedarone in combination with apixaban or warfarin. No significant differences in favour of either drug combination were found.

Long-term adherence to dronedarone in patients with atrial arrhythmias

Long-term adherence to dronedarone in patients with atrial arrhythmias

Use of MKSAP 16 for American Board of Internal Medicine Examination.

In reviewing MKSAP 16 in preparation for an American Board of Internal Medicine recertification examination, Dr. Melissa Gennarelli, an internist at Westchester Medical Center/New York Medical College, asked Dr. Wilbert S. Aronow, a Professor of Cardiology at Westchester Medical Center/New York Medical College, 2 questions. The first question was why he currently recommends that diabetics with hypertension should have their systolic blood pressure reduced to < 140 mm Hg when MKSAP 16 (page 29 of Cardiovascular Medicine) recommends a systolic blood pressure goal of < 130 mm Hg. The second question was why he does not use dronedarone to treat high-risk patients with permanent atrial fibrillation when MKSAP 16 (page 52 of Cardiovascular Medicine) recommends the use of dronedarone in patients with atrial fibrillation to reduce hospitalization for cardiovascular events or mortality. In reply to the first question, Dr. Aronow stated that on the basis of clinical trial data, the 2009 European Society of Hypertension guidelines [1], the American College of Cardiology Foundation/American Heart Association 2011 expert consensus document on hypertension in the elderly [2], and an excellent review article on this topic [3] recommend a systolic blood pressure goal of <140 mm Hg in diabetics with hypertension. The 2013 American Diabetes Association guidelines recommend a systolic blood pressure goal of < 140 mm Hg in most diabetics with hypertension [4]. In reply to the second question, Dr. Aronow stated that the Permanent Atrial Fibrillation Outcome Study Using Dronedarone on Top of Standard Therapy (PALLAS) randomized 3,236 patients with permanent atrial fibrillation and risk factors for major vascular events to treatment with dronedarone or double-blind placebo [5]. This study was stopped for safety reasons with a median follow-up of 3.5 months because dronedarone increased the rates of heart failure, stroke, and cardiovascular mortality in patients with permanent atrial fibrillation at risk for major vascular events [5].

Efficacy and safety of dronedarone in patients previously treated with other antiarrhythmic agents.

Currently available antiarrhythmic drugs (AADs) for the prevention of atrial fibrillation (AF)/atrial flutter (AFL) suffer from incomplete efficacy and poor tolerability. Dronedarone could represent an effective and safe option in patients previously treated with AADs, especially class Ic AADs and sotalol. Retrospective analysis of 2 double-blind, parallel-group trials (EURIDIS [European Trial in Atrial Fibrillation or Flutter Patients Receiving Dronedarone for the Maintenance of Sinus Rhythm] and ADONIS [American-Australian-African Trial With Dronedarone in Atrial Fibrillation or Flutter Patients for the Maintenance of Sinus Rhythm]) comparing the efficacy and safety of dronedarone with placebo over 12 months. The primary end point was AF/AFL recurrence in patients previously treated with another AAD that was discontinued for whatever reason prior to randomization. In patients previously treated with any AADs, dronedarone decreased the risk of AF recurrence by 30.4% vs placebo (hazard ratio [HR]: 0.70; 95% confidence interval [CI]: 0.59-0.82; P < 0.001). In patients previously treated with a class Ic agent, dronedarone decreased the risk of recurrence by 31.4% (HR: 0.69; 95% CI: 0.53-0.89; P = 0.004), whereas in patients previously treated with sotalol, dronedarone showed a trend toward a decrease of risk of recurrence (HR: 0.86; 95% CI: 0.67-1.11; P = 0.244). Dronedarone was equally effective irrespective of whether class Ic or sotalol were stopped for lack of efficacy or adverse events (AEs). Discontinuation rates were similar in the 2 groups (55.9% vs 43.1%), as were incidence of AEs and serious AEs. Dronedarone seems to be effective in preventing AF recurrences in patients without permanent AF previously treated with other AADs, even if those were discontinued for lack of efficacy. Dronedarone appears to be well tolerated even in patients who already had tolerability issues with AADs.

An individual patient-based meta-analysis of the effects of dronedarone in patients with atrial fibrillation.

Dronedarone is a non-iodinated benzofuran derivative with antiarrhythmic properties. In placebo-controlled atrial fibrillation (AF) trials, the drug was found to have divergent effects on endpoints such as cardiovascular death or hospitalization. The objective of this meta-analysis of all placebo-controlled studies was to provide insights on possible reasons for these divergent effects. Individual data on 9664 patients were used from all AF placebo-controlled studies. The primary outcome measure was cardiovascular death. Cardiovascular hospitalization and hospitalization for heart failure were secondary endpoints. Predefined procedures were used to reduce inter-study heterogeneity adjusting for important baseline variables using a Cox model. Despite adjustments, a significant inter-trial heterogeneity of the outcome of cardiovascular mortality persisted (P-value of 0.005 for the treatment effect × study interaction). Further analyses were conducted in subgroups based on baseline clinical criteria: digoxin co-prescription, advanced heart failure, coronary artery disease, or the presence of permanent AF. These analyses allowed the calculation of a global treatment effect in two important patient subgroups, those with permanent AF in whom there was harm with respect to cardiovascular mortality [hazard ratio (HR) = 2.32; 95% confidence interval (CI) 1.13-4.75] and hospitalization for heart failure (HR = 1.674; 95% CI 1.05-2.67); and those with non-permanent AF in whom there was benefit in terms of cardiovascular hospitalization [HR = 0.751 95% CI (0.68-0.83)]. This meta-analysis demonstrates significant heterogeneity of dronedarone treatment effects across the placebo-controlled randomized trials. The most important predictor of a harmful effect of dronedarone on cardiovascular death and heart failure hospitalization was the presence of permanent AF.

PS-042 Safety profile of amiodarone and dronedarone in patients treated with oral vitamin K antagonists

BackgroundAmiodarone and dronedarone decrease the risk of recurrences in patients with paroxysmal or persistent atrial fibrillation or atrial flutter. Both drugs are P-glycoprotein inhibitors and they are substrate/inhibitor of CYP3A4.PurposeTo...

Evaluation of dronedarone as a therapeutic option for patients with atrial fibrillation.

Atrial fibrillation (AF) is the predominant dysrhythmia affecting approximately 2·4 million people in the United States and over 6 million Europeans. Dronedarone is a benzofuran derivative of amiodarone newly approved in 2009 for the treatment of AF. Here, we comment on the efficacy and safety of dronedarone in patients with AF. Eight randomized controlled trials were analysed in this article. Several trials showed that dronedarone therapy delayed AF recurrence, controlled ventricular rate and reduced incidences of hospitalization or death. However, some of the studies were terminated early due to an excess mortality rate. Further studies on long-term safety and trials on direct comparison to rate controlling medications are suggested to obtain additional insight of dronedarone. Dronedarone reduces the incidence of AF recurrences, hospitalization and death in patients with paroxysmal or persistent AF. However, dronedarone should not be used in high-risk patients with permanent AF or patients with unstable chronic heart failure (HF) due to safety concerns.

Risk of Cardiovascular Events, Stroke, Congestive Heart Failure, Interstitial Lung Disease, and Acute Liver Injury: Dronedarone versus Amiodarone and Other Antiarrhythmics.

No published studies have evaluated the risks of cardiovascular (CV) events, stroke, congestive heart failure (CHF), interstitial lung disease (ILD), and severe acute liver injury (ALI) related to antiarrhythmics treatment in real-world clinical practice setting. We examined the relationship between the above events and the selected antiarrhythmics in the real-world setting in the US. Using a retrospective cohort design, the hazard ratios of the outcome events were analyzed from 10,455 adult patients with a diagnosis of atrial fibrillation/atrial flutter and a new treatment with dronedarone (comparison drug), amiodarone, sotalol, flecainide, or propafenone between 07/20/2009 and 12/31/2010 from the Clinformatics Data MartTM database. The patients were followed until: 1) switch to another antiarrhythmic drug, 2) occurrence of the outcome event, 3) end of enrollment, or 4) end of the study period, whichever occurred first. No significant differences were observed in the hazard ratios of the outcome events between dronedarone, amiodarone, and the other antiarrhythmics, except that amiodarone was associated with a higher risk of CV events (adjusted HR = 1.7, 95%CI: 1.1-2.4) and stroke (adjusted HR = 2.0, 95%CI: 1.33.2), compared to dronedarone, especially amongst patients without a CHF history (adjusted HR = 2.4, 95%CI: 1.4-3.8 and 2.2, 95%CI: 1.23.9). A higher risk of CHF was also associated with amiodarone in patients without history of CHF at baseline (adjusted HR = 2.7, 95%CI: 2.03.6). In this real-world investigation, no difference in risk was observed between dronedarone, sotalol, and propafenone initiators for CV events, stroke, CHF, ILD, and ALI. Amiodarone was associated with higher risks of CV events, stroke, and CHF than dronedarone in patients without a CHF history, indicating dronedarone could be an alternative therapy option with lower risk of CV events than amiodarone for the above patients.

Effect of dronedarone on clinical end points in patients with atrial fibrillation and coronary heart disease: insights from the ATHENA trial

AimsThis study aimed to assess safety and cardiovascular outcomes of dronedarone in patients with paroxysmal or persistent atrial fibrillation (AF) with coronary heart disease (CHD). Coronary heart disease is prevalent among AF patients and limits antiarrhythmic drug use because of their potentially life-threatening ventricular proarrhythmic effects.Methods and resultsThis post hoc analysis evaluated 1405 patients with paroxysmal or persistent AF and CHD from the ATHENA trial. Follow-up lasted 2.5 years, during which patients received either dronedarone (400 mg twice daily) or a double-blind matching placebo. Primary outcome was time to first cardiovascular hospitalization or death due to any cause. Secondary end points included first hospitalization due to cardiovascular events. The primary outcome occurred in 350 of 737 (47%) placebo patients vs. 252 of 668 (38%) dronedarone patients [hazard ratio (HR) = 0.73; 95% confidence interval (CI) = 0.62–0.86; P = 0.0002] without a significant increase in number of adverse events. In addition, 42 of 668 patients receiving dronedarone suffered from a first acute coronary syndrome compared with 67 of 737 patients from the placebo group (HR = 0.67; 95% CI = 0.46–0.99; P = 0.04).ConclusionIn this post hoc analysis, dronedarone on top of standard care in AF patients with CHD reduced cardiovascular hospitalization or death similar to that in the overall ATHENA population, and reduced a first acute coronary syndrome. Importantly, the safety profile in this subpopulation was also similar to that of the overall ATHENA population, with no excess in proarrhythmias. The mechanism of the cardiovascular protective effects is unclear and warrants further investigation.

The funny and not-so-funny effects of dronedarone

The funny and not-so-funny effects of dronedarone

Which Patient is Most Likely to Benefit From Dronedarone? Analysis From the Magdeburg Dronedarone Registry (MADRE Study)

Based on an analysis of the Magdeburg Dronedarone Registry data we sought to determine which patients could benefit from dronedarone therapy regarding rhythm control. The study included 191 patients (85 women) aged 63 ± 10 years with a history of paroxysmal or persistent AF and a follow-up of 14 ± 5 months. The total AF recurrence rate was 67% and lone AF was significantly more often associated with AF recurrences than non-lone AF (84% vs. 62%, P = .01). Arterial hypertension, treated coronary artery disease, and diabetes mellitus were not significantly related to AF recurrences (64%, 67%, 58% resp. P = .3). Response rate to dronedarone in patients with slightly increased left atrial size was significantly greater than in patients with normal or markedly increased left atrial size (47%, 16%, 27% resp., P = .001). The rate of adverse effects was 32% in the study sample, and was significantly lower in patients with lone AF as compared to those with non-lone AF (11% vs. 37%, P = .002). The body mass index was a predictor neither of response rate nor adverse effects. The results suggest that dronedarone is more effective in patients with non-lone AF and slightly increased left atrial size.

Cost-Effectiveness of Dronedarone in Patients With Atrial Fibrillation in the ATHENA Trial

BackgroundThe ATHENA trial randomized 4628 patients with atrial fibrillation (AF) or atrial flutter, aged ≥ 70 years with risk factors or ≥ 75 years without risk factors, to receive 400 mg dronedarone twice daily or placebo in addition to standard therapy. Our objective was to evaluate the cost-effectiveness of dronedarone from a Canadian health care perspective based on resource utilization and cardiovascular hospitalization or death in ATHENA. MethodsData on medical resource utilization (cardiovascular hospitalizations, hospitalization because of treatment-related adverse events, outpatient examinations and procedures, study drug and concomitant medications) were aggregated for all randomized patients during the entire trial period (mean 21 months). Effectiveness was measured using the total number of avoided cardiovascular hospitalizations and deaths from any cause, and projected survival and quality-adjusted survival using life tables adjusted for AF mortality and data on determinants of utility in AF. We used standard unit costs from Canada (2008), discounting costs and effects at 5% per year. ResultsPatients receiving dronedarone incurred a mean total cost (undiscounted) of CAD$7402 during the trial period, compared with CAD$6708 for patients receiving placebo. The cost of dronedarone was partly offset by savings for cardiovascular hospitalizations and concomitant medications. On average, patients taking dronedarone experienced 0.18 fewer events (cardiovascular hospitalizations or death). The cost per event avoided was CAD$3807, the cost per life-year gained was CAD$5204, and the cost per quality-adjusted life-years was CAD$7560. ConclusionsCompared with generally accepted thresholds, our results indicate that treatment with dronedarone as in ATHENA is cost-effective.

Usefulness of Dronedarone in Patients With Atrial Arrhythmias

Dronedarone is a novel class III antiarrhythmic drug with moderate efficacy in preventing atrial arrhythmias. However, only few data from the real-world use of dronedarone with limited electrocardiographic monitoring are available. The investigators report the incidence, timing, and reasons for discontinuation of dronedarone; maintenance of sinus rhythm; and atrial arrhythmia recurrence patterns in 120 consecutive patients with atrial fibrillation (AF; n = 91) or non-isthmus-dependent atrial flutter (n = 29) treated with dronedarone (400 mg twice daily). Rhythm control was assessed with serial 7-day Holter electrocardiography after 4 weeks and after 6 to 9 months. After drug initiation, dronedarone was discontinued in 19 patients (16%) because of inefficacy (n = 7 [6%]) or adverse events (n = 12 [10%]). At 4 weeks, 44 patients (37%) had stopped taking dronedarone because of inefficacy (n = 27 [23%]) or adverse events (n = 17 [14%]). After 6 to 9 months, 25 patients (21%) had discontinued dronedarone because of clinical inefficacy (n = 16 [13%]) or adverse events (n = 9 [8%]). Overall, dronedarone was still used after 6 to 9 months in 32 patients (27%). Maintenance of sinus rhythm was achieved in 40 patients (33%) after 4 weeks and in 24 patients (20%) after 6 to 9 months. Reversal from persistent to paroxysmal arrhythmias was observed in 23 patients, (29%) whereas progression from paroxysmal to persistent arrhythmias occurred in 6 patients (15%). Conversion from AF to non-isthmus-dependent atrial flutter was noted in 10 patients (13%). In conclusion, dronedarone is associated with frequent adverse events and moderate antiarrhythmic efficacy requiring discontinuation in most patients within the first 9 months of use, and there is a prevalent reversal from persistent to paroxysmal but also from paroxysmal to persistent atrial arrhythmias and from AF to non-isthmus-dependent atrial flutter.