Antiarrhythmic drugs (AADs) are widely prescribed to treat both ventricular and supraventricular arrhythmias. Although the efficacy of catheter ablation is often superior to AADs, medical rhythm control remains an important treatment modality.^1,2 The choice of AAD is affected by efficacy for treatment of the specific arrhythmia, comorbidities including structural heart disease and chronic kidney disease that may contraindicate the use of certain drugs, tolerability, long-term toxicities, and need for inpatient initiation.

As results from landmark studies are reported and guidelines updated over time, practice patterns evolve. Important trials affecting the use of AADs include the CAST (Cardiac Arrhythmia Suppression Trial) and SWORD (Survival with Oral D-Sotalol Study), which demonstrated that AADs could increase mortality.^3,4 Safety concerns have also arisen over time for individual agents, particularly amiodarone.⁵ With this evolving landscape, we aimed to investigate real-world trends in AAD use over a 13-year period.

Data were obtained from the Optum Clinformatics Data Mart, a de-identified database of commercial and Medicare Advantage claims. The Institutional Review Board determined that this research was exempt from the regulatory requirements of the federal Common Rule. We identified all patients who filled a prescription for amiodarone, disopyramide, dofetilide, dronedarone, flecainide, mexiletine, propafenone, quinidine, or sotalol between January 2004 and December 2016. Rates of AAD use were calculated per 100,000 patients among a total of 63 million unique individuals in the database. Arrhythmia and comorbid diagnoses were identified using International Classification of Diseases, Ninth Revision and Tenth Revision diagnostic codes. Arrhythmia diagnoses were combined into meaningful categories including atrial fibrillation and flutter; ventricular tachycardia and fibrillation; and supraventricular tachycardia.

We identified 406 181 patients who were prescribed 1 or more AADs between 2004 and 2016. Patients were 67.4±12.7 years old and mostly male (59%) and white (72%). A majority of patients had hypertension (82.3%) and ischemic heart disease (54.9%). A substantial proportion had cardiomyopathy (45.6%), valvular heart disease (44.1%), and chronic kidney disease (23.9%), and a small number had liver disease (5.6%). An implantable cardioverter-defibrillator or permanent pacemaker was present in 10.2% and 10.5% of patients, respectively. The most common arrhythmia was atrial fibrillation or flutter (82.2%), followed by ventricular tachycardia or fibrillation (17.8%) and supraventricular tachycardia (16.2%). Despite the known risk of organ toxicity, patients prescribed amiodarone frequently had chronic obstructive lung disease (40.9%) or liver disease (6.0%). Similarly, patients prescribed sotalol or dofetilide commonly had chronic kidney disease (18.1%), whereas those prescribed flecainide and propafenone (Vaughan Williams Class 1C AADs) often had cardiomyopathy (21.7%), ischemic (32.1%), or valvular heart disease (36.81%).

The prevalence of each arrhythmia within the entire cohort of 63 million increased dramatically over the study period (Figure [A]). For example, atrial fibrillation or flutter was present in 142 per 100 000 patients in the entire database in 2004 and increased to 756 per 100 000 by 2016. During this time, the number of patients prescribed AADs increased from 345 to 979 per 100 000, with the most substantial growth noted in prescriptions for amiodarone, sotalol, flecainide, and dofetilide (Figure [B]). Two AADs, quinidine and disopyramide, were prescribed less commonly in 2016 than in 2004 (2 versus 9 and 3 versus 9 per 100 000 patients, respectively, P<0.001 for both). Dronedarone, which was approved by the US Food and Drug Administration in 2009 and issued a Black Box warning in 2011, decreased from its peak of 11% of AAD prescriptions in 2011 to only 6% by 2016.

Figure. Increasing prevalence of arrhythmias and prescriptions for antiarrhythmic drugs.A, Prevalence of arrhythmia diagnoses from 2004 to 2016. B, Rate of filled prescriptions for the most common antiarrhythmic drugs from 2004 to 2016.

In this large national cohort of adult patients, we found that the rate of AAD prescription nearly tripled between 2004 and 2016. The most substantial increases were observed among amiodarone, sotalol, flecainide, and dofetilide, each of which are commonly used to treat atrial arrhythmias. Atrial fibrillation and flutter were the most common arrhythmias treated with AADs throughout the study period. The prevalence of these diagnoses increased more than 5-fold from 2004 to 2016 among patients in the database. These dramatic increases are likely multifactorial secondary to true increases in prevalence of disease, improved diagnostic recognition through more intensive monitoring, and enhanced coding practices. This retrospective study is inherently limited by the use of administrative claims. Although we used validated International Classification of Diseases codes, we cannot exclude the possibility of incomplete or inaccurate classification. We chose not to include other common antiarrhythmic medications such as β-blockers and calcium channel blockers, given their more frequent uses for nonarrhythmia indications. Last, our population was commercially insured and nonelderly, potentially limiting generalizability of our findings.

The marked increase in use of AADs raises important safety concerns. Although potentially efficacious, AADs can also cause toxicity and proarrhythmia. Medical comorbidities are highly prevalent among patients treated with AADs, and may limit AAD choice. It is essential that prescribers and other healthcare providers be vigilant about the safety profile, contraindications, and interactions of these increasingly used medications.

Supported by the Pennsylvania Steel Company EP Research Fund.

None.

https://www.ahajournals.org/journal/circ

The data used for this study are the property of Optum and were used by the investigators through a contractual agreement. Inquiries about obtaining similar data can be directed to Optum at https://www.optum.com/solutions/life-sciences/life-sciences-contact.html.

抗心律不齐药物（AAD）广泛用于治疗室性和室上性心律失常。尽管导管消融的疗效通常优于AAD，但控制心律仍是重要的治疗方式。^1,2，AAD的选择受治疗特定心律失常的功效，结构性心脏病和慢性肾脏疾病等合并症的影响，这些合并症可能会禁止某些药物的使用，耐受性，长期毒性以及需要住院治疗。

随着具有里程碑意义的研究成果的报道和指南的不断更新，实践模式也在不断发展。影响AAD使用的重要试验包括CAST（心脏心律失常抑制试验）和SWORD（口服D-索他洛尔生存研究），这表明AAD可以增加死亡率。^3,4随着时间的流逝，个别药剂，尤其是胺碘酮的安全问题也引起关注。⁵随着形势的发展，我们旨在调查13年内AAD使用的现实趋势。

数据是从Optum Clinformatics Data Mart获得的，该数据库是商业和Medicare Advantage索赔的去身份数据库。机构审查委员会认为该研究不受联邦《通用规则》的监管要求的约束。我们确定了所有在2004年1月至2016年12月之间填写了胺碘酮，二吡酰胺，多非利特，决奈达隆，氟卡尼，美西律，普罗帕酮，奎尼丁或索他洛尔处方的患者。在总共6300万独特患者中，每10万患者计算AAD的使用率数据库中的个人。心律失常和合并症的诊断采用《国际疾病分类》，第九版和第十版诊断代码。心律失常的诊断被分为有意义的类别，包括房颤和扑动；室性心动过速和纤颤；和室上性心动过速。

我们确定了2004年至2016年间406 181例接受1次或更多AAD处方治疗的患者。患者年龄为67.4±12.7岁，主要为男性（59％）和白人（72％）。大多数患者患有高血压（82.3％）和缺血性心脏病（54.9％）。很大一部分患有心肌病（45.6％），瓣膜性心脏病（44.1％）和慢性肾脏病（23.9％），少数患有肝病（5.6％）。植入式心脏复律除颤器或永久起搏器分别存在于10.2％和10.5％的患者中。最常见的心律失常是房颤或扑动（82.2％），其次是室性心动过速或纤颤（17.8％）和室上性心动过速（16.2％）。尽管已知存在器官毒性的风险，但开具胺碘酮的患者经常患有慢性阻塞性肺疾病（40.9％）或肝脏疾病（6。0％）。同样，开具索他洛尔或多非利特的患者通常患有慢性肾脏疾病（18.1％），而开立氟卡尼和普罗帕酮（Vaughan Williams 1C类AAD）的患者经常患有心肌病（21.7％），局部缺血（32.1％）或瓣膜性心脏病（36.81）。 ％）。

在整个研究期间，整个心律失常的患病率达6300万（图[A]）。例如，2004年整个数据库中，每10万名患者中有142名出现心房纤颤或扑动，到2016年，这一数字增加到每10万名中756名。在此期间，开具AAD的患者人数从345个增至979个（十万个），胺碘酮，索他洛尔，氟卡尼和多非利特的处方中出现了最显着的增长（图[B]）。两个AADS，奎尼丁和丙吡胺，均在2016以下常用的处方比2004（2相对于图9和3与9每100名患者，分别P两者均<0.001）。Dronedarone于2009年获得美国食品和药物管理局的批准，并于2011年发布了黑匣子警告，从2011年AAD处方药峰值的11％降至2016年的6％。

数字。 心律失常的流行和抗心律失常药物的处方。A，从2004年至2016年诊断为心律失常的流行率。B，从2004年至2016年为最常见的抗心律不齐药物开具的处方率。

在这个庞大的全国成年患者队列中，我们发现AAD处方的比率在2004年至2016年期间几乎增加了两倍。在胺碘酮，索他洛尔，氟卡尼特和多非利特中观察到增幅最大，这两种药物通常用于治疗房性心律不齐。在整个研究期间，心房纤颤和扑动是最常见的用AAD治疗的心律不齐。从2004年到2016年，这些诊断的患病率在数据库中的患者中增加了5倍以上。这些急剧增加可能是继疾病流行率的真正增加之后的多因素因素，通过更深入的监控和增强的编码实践，改善了诊断识别度。这项回顾性研究固有地受到行政要求的限制。虽然我们使用经过验证国际疾病分类代码，我们不能排除分类不完整或不正确的可能性。考虑到非心律不齐适应症的使用频率较高，我们选择不包括其他常见的抗心律失常药物，例如β受体阻滞剂和钙通道阻滞剂。最后，我们的人群有商业保险且非老年人，这可能会限制我们研究结果的普遍性。

使用AAD的明显增加引起了重要的安全隐患。尽管可能有效，但AAD也会引起毒性和心律失常。医学合并症在接受AAD治疗的患者中非常普遍，可能会限制AAD的选择。开处方者和其他医疗保健提供者必须警惕这些日益使用的药物的安全性，禁忌症和相互作用。

由宾夕法尼亚钢铁公司EP研究基金资助。

没有。

https://www.ahajournals.org/journal/circ

本研究使用的数据是Optum的财产，研究人员通过合同协议使用了这些数据。有关获取类似数据的查询，请访问https://www.optum.com/solutions/life-sciences/life-sciences-contact.html。