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Trends in Antiarrhythmic Drug Use Among Patients in the United States Between 2004 and 2016

2020; Lippincott Williams & Wilkins; Volume: 141; Issue: 11 Linguagem: Inglês

10.1161/circulationaha.119.044109

1524-4539

Timothy M. Markman, Zhi Geng, Andrew E. Epstein, Saman Nazarian, Rajat Deo, Francis E. Marchlinski, Peter W. Groeneveld, David S. Frankel,

Cardiac Arrhythmias and Treatments

HomeCirculationVol. 141, No. 11Trends in Antiarrhythmic Drug Use Among Patients in the United States Between 2004 and 2016 Free AccessLetterPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessLetterPDF/EPUBTrends in Antiarrhythmic Drug Use Among Patients in the United States Between 2004 and 2016 Timothy M. Markman, MD, Zhi Geng, MD, MPH, Andrew E. Epstein, MD, Saman Nazarian, MD, PhD, Rajat Deo, MD, Francis E. Marchlinski, MD, Peter W. Groeneveld, MD and David S. Frankel, MD Timothy M. MarkmanTimothy M. Markman Cardiovascular Division (T.M.M., A.E.E., S.N., R.D., F.E.M., D.S.F.), Perelman School of Medicine , Zhi GengZhi Geng Division of General Internal Medicine (Z.G., P.W.G.), Perelman School of Medicine Center for Cardiovascular Outcomes, Quality, and Evaluative Research (Z.G., P.W.G.), University of Pennsylvania, Philadelphia , Andrew E. EpsteinAndrew E. Epstein Cardiovascular Division (T.M.M., A.E.E., S.N., R.D., F.E.M., D.S.F.), Perelman School of Medicine Corporal Michael J. Crescenz Veterans Affairs Medical Center, Philadelphia, PA (A.E.E., P.W.G.). , Saman NazarianSaman Nazarian Cardiovascular Division (T.M.M., A.E.E., S.N., R.D., F.E.M., D.S.F.), Perelman School of Medicine , Rajat DeoRajat Deo Cardiovascular Division (T.M.M., A.E.E., S.N., R.D., F.E.M., D.S.F.), Perelman School of Medicine , Francis E. MarchlinskiFrancis E. Marchlinski Cardiovascular Division (T.M.M., A.E.E., S.N., R.D., F.E.M., D.S.F.), Perelman School of Medicine , Peter W. GroeneveldPeter W. Groeneveld Division of General Internal Medicine (Z.G., P.W.G.), Perelman School of Medicine Center for Cardiovascular Outcomes, Quality, and Evaluative Research (Z.G., P.W.G.), University of Pennsylvania, Philadelphia Corporal Michael J. Crescenz Veterans Affairs Medical Center, Philadelphia, PA (A.E.E., P.W.G.). and David S. FrankelDavid S. Frankel David S. Frankel, MD, Hospital of the University of Pennsylvania, 3400 Spruce Street, 9 Founders Pavilion, Philadelphia, PA 19104. Email E-mail Address: [email protected] Cardiovascular Division (T.M.M., A.E.E., S.N., R.D., F.E.M., D.S.F.), Perelman School of Medicine Originally published16 Mar 2020https://doi.org/10.1161/CIRCULATIONAHA.119.044109Circulation. 2020;141:937–939Antiarrhythmic 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.Download figureDownload PowerPointFigure. 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.Sources of FundingSupported by the Pennsylvania Steel Company EP Research Fund.DisclosuresNone.Footnoteshttps://www.ahajournals.org/journal/circThe 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.David S. Frankel, MD, Hospital of the University of Pennsylvania, 3400 Spruce Street, 9 Founders Pavilion, Philadelphia, PA 19104. Email david.[email protected]upenn.eduReferences1. Wilber DJ, Pappone C, Neuzil P, De Paola A, Marchlinski F, Natale A, Macle L, Daoud EG, Calkins H, Hall B, et al; ThermoCool AF Trial Investigators. Comparison of antiarrhythmic drug therapy and radiofrequency catheter ablation in patients with paroxysmal atrial fibrillation: a randomized controlled trial.JAMA. 2010; 303:333–340. doi: 10.1001/jama.2009.2029CrossrefMedlineGoogle Scholar2. Sapp JL, Wells GA, Parkash R, Stevenson WG, Blier L, Sarrazin JF, Thibault B, Rivard L, Gula L, Leong-Sit P, et al. Ventricular tachycardia ablation versus escalation of antiarrhythmic drugs.N Engl J Med. 2016; 375:111–121. doi: 10.1056/NEJMoa1513614CrossrefMedlineGoogle Scholar3. Waldo AL, Camm AJ, deRuyter H, Friedman PL, MacNeil DJ, Pauls JF, Pitt B, Pratt CM, Schwartz PJ, Veltri EP. Effect of d-sotalol on mortality in patients with left ventricular dysfunction after recent and remote myocardial infarction. The SWORD Investigators. Survival With Oral d-Sotalol.Lancet. 1996; 348:7–12. doi: 10.1016/s0140-6736(96)02149-6CrossrefMedlineGoogle Scholar4. Epstein AE, Hallstrom AP, Rogers WJ, Liebson PR, Seals AA, Anderson JL, Cohen JD, Capone RJ, Wyse DG. Mortality following ventricular arrhythmia suppression by encainide, flecainide, and moricizine after myocardial infarction. The original design concept of the Cardiac Arrhythmia Suppression Trial (CAST).JAMA. 1993; 270:2451–2455.CrossrefMedlineGoogle Scholar5. Wyse DG, Waldo AL, DiMarco JP, Domanski MJ, Rosenberg Y, Schron EB, Kellen JC, Greene HL, Mickel MC, Dalquist JE, et al; Atrial Fibrillation Follow-up Investigation of Rhythm Management (AFFIRM) Investigators. A comparison of rate control and rhythm control in patients with atrial fibrillation.N Engl J Med. 2002; 347:1825–1833. doi: 10.1056/NEJMoa021328CrossrefMedlineGoogle Scholar Previous Back to top Next FiguresReferencesRelatedDetailsCited ByCamm A, Blomström‐Lundqvist C, Boriani G, Goette A, Kowey P, Merino J, Piccini J, Saksena S and Reiffel J (2022) AIM‐AF: A Physician Survey in the United States and Europe, Journal of the American Heart Association, 11:6, Online publication date: 15-Mar-2022. Heijman J and Dobrev D (2022) Arrhythmias Comprehensive Pharmacology, 10.1016/B978-0-12-820472-6.00082-7, (432-468), . Eberly L and Dixit S (2021) Editorial commentary: Factors underlying improved mortality in patients with atrial fibrillation, Trends in Cardiovascular Medicine, 10.1016/j.tcm.2020.11.004, 31:8, (474-475), Online publication date: 1-Nov-2021. Bezabhe W, Bereznicki L, Radford J, Salahudeen M, Garrahy E, Wimmer B, Bindoff I and Peterson G (2021) Ten‐year trends in prescribing of antiarrhythmic drugs in Australian primary care patients with atrial fibrillation, Internal Medicine Journal, 10.1111/imj.15514, 51:10, (1732-1735), Online publication date: 1-Oct-2021. Heijman J, Sutanto H, Crijns H, Nattel S and Trayanova N (2021) Computational models of atrial fibrillation: achievements, challenges, and perspectives for improving clinical care, Cardiovascular Research, 10.1093/cvr/cvab138, 117:7, (1682-1699), Online publication date: 16-Jun-2021. Nattel S, Sager P, Hüser J, Heijman J and Dobrev D (2021) Why translation from basic discoveries to clinical applications is so difficult for atrial fibrillation and possible approaches to improving it, Cardiovascular Research, 10.1093/cvr/cvab093, 117:7, (1616-1631), Online publication date: 16-Jun-2021. Akoum N (2021) Antiarrhythmic drug choices for newly diagnosed atrial fibrillation—Patterns and potential implications, Journal of Cardiovascular Electrophysiology, 10.1111/jce.15008, 32:6, (1538-1539), Online publication date: 1-Jun-2021. Heijman J, Hohnloser S and Camm A (2021) Antiarrhythmic drugs for atrial fibrillation: lessons from the past and opportunities for the future, EP Europace, 10.1093/europace/euaa426, 23:Supplement_2, (ii14-ii22), Online publication date: 10-Apr-2021. March 17, 2020Vol 141, Issue 11 Advertisement Article InformationMetrics © 2020 American Heart Association, Inc.https://doi.org/10.1161/CIRCULATIONAHA.119.044109PMID: 32176541 Originally publishedMarch 16, 2020 Keywordssupraventricular tachycardiaantiarrhythmic drugsarrhythmiasventricular tachycardiaatrial fibrillationPDF download Advertisement SubjectsArrhythmiasElectrophysiology