Arrhythmias and Conduction Disturbances
Antiarrhythmic Drug Use in Patients <65 Years With Atrial Fibrillation and Without Structural Heart Disease

https://doi.org/10.1016/j.amjcard.2014.11.005Get rights and content

Little is known in clinical practice about antiarrhythmic drug (AAD) use in patients with atrial fibrillation (AF) (particularly younger ones) who do not have structural heart disease. Using the MarketScan database, we identified patients <65 years without known coronary artery disease or heart failure who had an AAD prescription claim (class Ic drug, amiodarone, sotalol, or dronedarone) after their first AF encounter. A multinomial logistic regression model was created to assess factors associated with using each available AAD compared with using class Ic drugs before and after dronedarone was marketed in the United States. Additionally, we used the Kaplan-Meier method to determine the rates of change in AAD use and discontinuation during the year after AAD initiation. Of 8,562 patients with AF, 35% received class Ic drugs, 34% amiodarone, 24% sotalol, and 7% dronedarone. The median patient age was 56 (interquartile range 49 to 61), and 34% were women. Both before and after dronedarone was marketed, there was a statistically significant lower likelihood of class Ic drug use versus other AAD use with increasing age, inpatient index AF encounter, and previous or concomitant anticoagulation therapy. During the 1 year after AAD initiation, the AAD change rate was 14% for class Ic drugs, 8% for amiodarone, 17% for sotalol, and 18% for dronedarone (p <0.001); the AAD discontinuation rate was 40% for class Ic drugs, 52% for amiodarone, 40% for sotalol, and 69% for dronedarone (p <0.001). In conclusion, we found extensive use of amiodarone that may be inconsistent with guideline recommendations and unexpectedly high rates of AAD discontinuation.

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Methods

The study cohort was obtained from the Thomas Reuters MarketScan Commercial Claims and Encounters Database. This database consists of inpatient, outpatient, and prescription claims data from US employers who provide health plans for their employees and employees' spouses and dependents. The MarketScan database has primarily been used for health care utilization and outcome studies of a variety of diseases, including AF.1, 2, 3 For purposes of this analysis, we obtained data on all patients with

Results

After excluding a small number of patients who initially received dofetilide (n = 46; Figure 1), a total of 8,562 patients <65 years with AF, but without CAD or heart failure, were included in the final study cohort. In this final cohort, use of a class Ic drug was found in 35% of patients, followed by amiodarone (34%), sotalol (24%), and dronedarone (7%). In those receiving a class Ic drug, 51.5% received flecainide and 48.5% received propafenone. Of the 8,562 patients in the overall study

Discussion

When the decision is made to use an AAD for the management of paroxysmal or persistent AF, selection of the most appropriate AAD should be based on patient-specific characteristics to minimize potential risk from the AAD. Patients without CAD and heart failure have a greater number of guideline-recommended AAD options,8, 9, 10 yet not all these options are optimal, given an individual patient's co-morbidities and each drug's unique properties. In this study, we provide the first description of

Acknowledgment

The authors would like to thank Louise Zimmer, MA, MPH, and Rosalia Blanco, MBA, for co-ordinating statistical resources. The authors would also like to thank Erin Hanley, MS, for editorial contributions to this report. Zimmer, Blanco, and Hanley did not receive compensation for their contributions, apart from the employment at the institution where this study was conducted.

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    These side effects are manifested in the adverse reactions of the heart, eyes, lungs, liver, dermatology, hematology, psychiatry, thyroid and neuromuscular, and epididymitis and syndrome of inappropriate secretion of antidiuretic hormone can even be caused by chronic amiodarone treatment (Biancatelli et al., 2019). Therefore, as the metabolism is slow and unpredictable, extracardiac toxicity is high and numerous drug interactions, almost one-third of patients cannot maintain long-term treatment for the severe adverse reactions (Allen LaPointe et al., 2015; Dan et al., 2018). Dronedarone (Fig. 1C), specifically developed for treating atrial fibrillation (AF), is a non-iodinated benzofuran, which was designed to retain the efficacy of amiodarone, with an improved safety profile.

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    In the TREAT-AF study, which employed propensity score matching, not only were hospitalization rates for AF or atrial flutter found to be lower with Class IC drugs, but also for cardiovascular disease, heart failure, and ischemic stroke.79 Another analysis using claims data80 found higher AF hospitalization rates with dronedarone and lower AF hospitalization rates with amiodarone, but no difference between sotalol and Class IC AADs. Thus, with the exception of amiodarone, the long-term efficacy of flecainide is comparable with other approved AADs.

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    Since randomized controlled trials in late 1980s and early 1990s showed that class I drugs were associated with increased mortality in patients with significant structural heart disease, largely due to life-threatening ventricular arrhythmias, attention has been redirected to the development of class III agents and amiodarone [4,6]. Amiodarone has long been used as a "drug of the last resort" but, currently, amiodarone is the most powerful and most commonly prescribed antiarrhythmic drug (AAD) for a „broad spectrum “of atrial and ventricular arrhythmias, accounting for approximately 30 % of the world AAD market [7]. However, due to its slow and unpredictable metabolism, high extracardiac toxicity and numerous drug-drug interactions, its use in clinical practice is a „two edged sword “and almost one-third of the patients are unable to sustain the long-term treatment due to serious adverse effects [6,7].

  • Flecainide: Electrophysiological properties, clinical indications, and practical aspects

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    Regardless of the guidelines recommendations, class IC drugs appear to be under used in everyday clinical practice, possibly due to an over perception of the severity of the side effects. A retrospective study on the American database “Thomas Reuters MarketsScan Commercial Claims and Encounters” documented an overall excessive use of amiodarone compared to IC drugs, while these latter were preferred in females, in patients with a history of atrial flutter, in patients with a known history of AF and in patients already treated with verapamil or diltiazem [29]. On the other hand, these drugs were avoided or scarcely used in older hospitalised patients, in patients with diabetes and in patients under anticoagulant treatment.

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