Cost Effectiveness of Antiarrhythmic Medications in Patients Suffering from Atrial Fibrillation


Atrial fibrillation (AF), a supraventricular tachycardia disorder, is the most common sustained cardiac arrhythmia affecting 1–2 % of the general population. Prevalence is highly related to age, with every fourth individual older than 40 years old developing AF during his lifetime. Due to an aging population, the prevalence of AF is estimated to at least double within the next 50 years. This article presents AF-related cost-of-illness studies and reviews 19 cost–effectiveness studies and six cost studies published roughly over the past decade, which have compared different antiarrhythmic medications for AF. A systematic literature search for studies published between June 2000 and December 2011 was conducted in PubMed using the combination of keywords ((atrial fibrillation OR atrial flutter) AND cost). Current cost–effectiveness analyses of dronedarone and the pill-in-the-pocket strategy are subject to substantial uncertainties with regard to clinical benefit. Comparing rate control with rhythm control, a cost–effectiveness advantage for rate control was shown in several but not all studies. Within antiarrhythmic drug treatments, magnesium added onto ibutilide was shown to be more cost effective than ibutilide alone. Comparing chemical and electrical cardioversion, the latter was recommended as more cost effective from the healthcare system perspective in all reviewed studies but one. Catheter ablation appeared more cost effective than antiarrhythmic drugs in the medium to long run after 3.2–63.9 years. Admissions to hospital, inpatient care and interventional procedures as well as mortality benefit are key drivers for the cost effectiveness of AF medications. No clear cost–effectiveness advantage emerged for one specific antiarrhythmic drug from the studies that compared antiarrhythmic agents. Rate control as well as catheter ablation appear more cost effective than rhythm control in the treatment of AF. Rate control treatment also seems more cost effective than electrical cardioversion in AF patients.

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  1. 1.

    Mewis C, Neuberger H-R, Böhm M. Atrial fibrillation (in German). Deutsche Medizinische Wochenschrift. 2006;131(50):2843–54 (quiz 2855–6).

    Google Scholar 

  2. 2.

    National Collaboration Centre for Chronic Conditions. Atrial fibrillation: national clinical guideline for management in primary and secondary care. London: Royal College of Physicians; 2006.

    Google Scholar 

  3. 3.

    Camm AJ, Kirchhof P, Lip GYH, Schotten U, Savelieva I, Ernst S, et al. Guidelines for the management of atrial fibrillation: the Task Force for the Management of Atrial Fibrillation of the European Society of Cardiology (ESC). Eur Heart J. 2010;31(19):2369–429.

    PubMed  Article  Google Scholar 

  4. 4.

    Go AS, Hylek EM, Phillips KA, Chang Y, Henault LE, Selby JV, et al. Prevalence of diagnosed atrial fibrillation in adults: national implications for rhythm management and stroke prevention: the AnTicoagulation and Risk factors In Atrial fibrillation (ATRIA) study. JAMA J Am Med Assoc. 2001;285(18):2370–5.

    Article  CAS  Google Scholar 

  5. 5.

    Naccarelli GV, Varker H, Lin J, Schulman KL. Increasing prevalence of atrial fibrillation and flutter in the United States. Am J Cardiol. 2009;104(11):1534–9.

    PubMed  Article  Google Scholar 

  6. 6.

    Heeringa J, van der Kuip DAM, Hofman A, Kors JA, van Herpen G, Stricker BHC, et al. Prevalence, incidence and lifetime risk of atrial fibrillation: the Rotterdam study. Eur Heart J. 2006;27(8):949–53.

    PubMed  Article  Google Scholar 

  7. 7.

    Lloyd-Jones DM, Wang TJ, Leip EP, Larson MG, Levy D, Vasan RS, et al. Lifetime risk for development of atrial fibrillation: the Framingham Heart Study. Circulation. 2004;110(9):1042–6.

    PubMed  Article  Google Scholar 

  8. 8.

    Blomstrom Lundqvist C, Lip GYH, Kirchhof P. What are the costs of atrial fibrillation? Europace 2011;13(Suppl 2):ii9–12.

  9. 9.

    Jönsson L, Eliasson A, Kindblom J, Almgren O, Edvardsson N. Cost of illness and drivers of cost in atrial fibrillation in Sweden and Germany. Appl Health Econ Health Policy. 2010;8(5):317–25.

    PubMed  Article  Google Scholar 

  10. 10.

    Brüggenjürgen B, Rossnagel K, Roll S, Andersson FL, Selim D, Müller-Nordhorn J, et al. The impact of atrial fibrillation on the cost of stroke: the Berlin Acute Stroke Study. Value Health. 2007;10(2):137–43.

    PubMed  Article  Google Scholar 

  11. 11.

    Ericson L, Bergfeldt L, Björholt I. Atrial fibrillation: the cost of illness in Sweden. Eur J Health Econ. 2011;12(5):479–87.

    PubMed  Article  Google Scholar 

  12. 12.

    Ringborg A, Nieuwlaat R, Lindgren P, Jönsson B, Fidan D, Maggioni AP, et al. Costs of atrial fibrillation in five European countries: results from the Euro Heart Survey on atrial fibrillation. Europace. 2008;10(4):403–11.

    PubMed  Article  Google Scholar 

  13. 13.

    Coyne KS, Paramore C, Grandy S, Mercader M, Reynolds M, Zimetbaum P. Assessing the direct costs of treating nonvalvular atrial fibrillation in the United States. Value Health. 2006;9(5):348–56.

    PubMed  Article  Google Scholar 

  14. 14.

    Le Heuzey J-Y, Paziaud O, Piot O, Said MA, Copie X, Lavergne T, et al. Cost of care distribution in atrial fibrillation patients: the COCAF study. Am Heart J. 2004;147(1):121–6.

    PubMed  Article  Google Scholar 

  15. 15.

    McBride D, Mattenklotz AM, Willich SN, Brüggenjürgen B. The costs of care in atrial fibrillation and the effect of treatment modalities in Germany. Value Health. 2009;12(2):293–301.

    PubMed  Article  Google Scholar 

  16. 16.

    Stewart S, Murphy NF, Walker A, McGuire A, McMurray JJV. Cost of an emerging epidemic: an economic analysis of atrial fibrillation in the UK. Heart. 2004;90(3):286–92.

    PubMed  Article  CAS  Google Scholar 

  17. 17.

    Kim MH, Lin J, Hussein M, Kreilick C, Battleman D. Cost of atrial fibrillation in United States managed care organizations. Adv Ther. 2009;26(9):847–57.

    PubMed  Article  Google Scholar 

  18. 18.

    Benkert D, Theres H, Wasem J, Aidelsburger P. Direkte Kosten in der Diagnostik und Behandlung von Patienten mit symptomatischem Vorhofflimmern in Deutschland. PharmacoEconomics German Research Articles. 2009;7(1):15–27.

    Article  Google Scholar 

  19. 19.

    Naccarelli GV, Johnston SS, Lin J, Patel PP, Schulman KL. Cost burden of cardiovascular hospitalization and mortality in ATHENA-like patients with atrial fibrillation/atrial flutter in the United States. Clin Cardiol. 2010;33(5):270–9.

    PubMed  Article  Google Scholar 

  20. 20.

    Friberg J, Buch P, Scharling H, Gadsbphioll N, Jensen GB. Rising rates of hospital admissions for atrial fibrillation. Epidemiology (Cambridge, Mass.). 2003;14(6):666–72.

    Article  Google Scholar 

  21. 21.

    Miyasaka Y, Barnes ME, Gersh BJ, Cha SS, Bailey KR, Seward JB, et al. Changing trends of hospital utilization in patients after their first episode of atrial fibrillation. Am J Cardiol. 2008;102(5):568–72.

    PubMed  Article  Google Scholar 

  22. 22.

    Wattigney WA, Mensah GA, Croft JB. Increasing trends in hospitalization for atrial fibrillation in the United States, 1985 through 1999: implications for primary prevention. Circulation. 2003;108(6):711–6.

    PubMed  Article  Google Scholar 

  23. 23.

    Kotowycz MA, Filion KB, Joza J, Dube D, Reynolds MR, Pilote L, et al. In-hospital management of atrial fibrillation: the CHADS2 score predicts increased cost. Can J Cardiol. 2011;27(4):506–13.

    PubMed  Article  Google Scholar 

  24. 24.

    Reynolds MR, Essebag V, Zimetbaum P, Cohen DJ. Healthcare resource utilization and costs associated with recurrent episodes of atrial fibrillation: the FRACTAL registry. J Cardiovasc Electrophysiol. 2007;18(6):628–33.

    PubMed  Article  Google Scholar 

  25. 25.

    Holstenson E, Ringborg A, Lindgren P, Coste F, Diamand F, Nieuwlaat R, et al. Predictors of costs related to cardiovascular disease among patients with atrial fibrillation in five European countries. Europace. 2011;13(1):23–30.

    PubMed  Article  Google Scholar 

  26. 26.

    Lumer G. Amiodarone reduces procedures and costs related to atrial fibrillation in a controlled clinical trial. Eur Heart J. 2002;23(13):1050–6.

    PubMed  Article  CAS  Google Scholar 

  27. 27.

    Teng MP, Catherwood LE, Melby DP. Cost effectiveness of therapies for atrial fibrillation: a review. Pharmacoeconomics. 2000;18(4):317–33.

    PubMed  Article  CAS  Google Scholar 

  28. 28.

    Marshall DA, Levy AR, Vidaillet H, Fenwick E, Slee A, Blackhouse G, et al. Cost–effectiveness of rhythm versus rate control in atrial fibrillation. Ann Intern Med. 2004;141(9):653–61.

    PubMed  Article  Google Scholar 

  29. 29.

    Kim MH, Klingman D, Lin J, Battleman DS. Patterns and predictors of discontinuation of rhythm-control drug therapy in patients with newly diagnosed atrial fibrillation. Pharmacotherapy. 2009;29(12):1417–26.

    PubMed  Article  Google Scholar 

  30. 30.

    Kim MH, Johnston SS, Chu B-C, Dalal MR, Schulman KL. Estimation of total incremental health care costs in patients with atrial fibrillation in the United States. Circ Cardiovasc Qual Outcomes. 2011;4(3):313–20.

    PubMed  Article  Google Scholar 

  31. 31.

    Lee WC, Lamas GA, Balu S, Spalding J, Wang Q, Pashos CL. Direct treatment cost of atrial fibrillation in the elderly American population: a Medicare perspective. J Med Econ. 2008;11(2):281–98.

    PubMed  Google Scholar 

  32. 32.

    Reinhold T, Lindig C, Willich SN, Brüggenjürgen B. The costs of atrial fibrillation in patients with cardiovascular comorbidities—a longitudinal analysis of German health insurance data. Europace. 2011;13(9):1275–80.

    PubMed  Article  Google Scholar 

  33. 33.

    Wyse DG, Waldo AL, DiMarco JP, Domanski MJ, Rosenberg Y, Schron EB, et al. A comparison of rate control and rhythm control in patients with atrial fibrillation. N Engl J Med. 2002;347(23):1825–33.

    PubMed  Article  CAS  Google Scholar 

  34. 34.

    Van Gelder IC, Hagens VE, Bosker HA, Kingma JH, Kamp O, Kingma T, et al. A comparison of rate control and rhythm control in patients with recurrent persistent atrial fibrillation. N Engl J Med. 2002;347(23):1834–40.

    PubMed  Article  Google Scholar 

  35. 35.

    Hohnloser SH, Kuck KH, Lilienthal J. Rhythm or rate control in atrial fibrillation—Pharmacological Intervention in Atrial Fibrillation (PIAF): a randomised trial. Lancet. 2000;356(9244):1789–94.

    PubMed  Article  CAS  Google Scholar 

  36. 36.

    Carlsson J, Miketic S, Windeler J, Cuneo A, Haun S, Micus S, et al. Randomized trial of rate-control versus rhythm-control in persistent atrial fibrillation: the Strategies of Treatment of Atrial Fibrillation (STAF) study. J Am Coll Cardiol. 2003;41(10):1690–6.

    PubMed  Article  Google Scholar 

  37. 37.

    Torp-Pedersen C, Crijns HJGM, Gaudin C, Page RL, Connolly SJ, Hohnloser SH. Impact of dronedarone on hospitalization burden in patients with atrial fibrillation: results from the ATHENA study. Europace. 2011;13(8):1118–26.

    PubMed  Article  Google Scholar 

  38. 38.

    McKenna C, Maund E, Sarowar M, Fox D, Stevenson M, Pepper C, et al. Dronedarone for the treatment of atrial fibrillation: a NICE single technology appraisal. PharmacoEconomics. 2012;30(1):35–46.

    PubMed  Article  Google Scholar 

  39. 39.

    Maund E, McKenna C, Sarowar M, Fox D, Stevenson M, Pepper C, et al. Dronedarone for the treatment of atrial fibrillation and atrial flutter. Health Technol Assess. 2010;14(Suppl. 2):55–62.

    PubMed  CAS  Google Scholar 

  40. 40.

    McKenna C, Maund E, Sarowar M, Fox D, Stevenson M, Pepper C, et al. Dronedarone for atrial fibrillation and atrial flutter: a single technology appraisal. York: Centre for Reviews and Dissemination and Centre for Health Economics; 2009.

    Google Scholar 

  41. 41.

    Kim MH, Lin J, Hussein M, Battleman D. Incidence and economic burden of suspected adverse events and adverse event monitoring during AF therapy. Curr Med Res Opin. 2009;25(12):3037–47.

    PubMed  Article  CAS  Google Scholar 

  42. 42.

    Chan PS, Vijan S, Morady F, Oral H. Cost–effectiveness of radiofrequency catheter ablation for atrial fibrillation. J Am Coll Cardiol. 2006;47(12):2513–20.

    PubMed  Article  Google Scholar 

  43. 43.

    Fenwick E, Marshall DA, Blackhouse G, Vidaillet H, Slee A, Shemanski L, et al. Assessing the impact of censoring of costs and effects on health-care decision-making: an example using the Atrial Fibrillation Follow-up Investigation of Rhythm Management (AFFIRM) study. Value Health. 2008;11(3):365–75.

    PubMed  Article  Google Scholar 

  44. 44.

    Fenwick E, Marshall DA, Levy AR, Nichol G. Using and interpreting cost–effectiveness acceptability curves: an example using data from a trial of management strategies for atrial fibrillation. BMC Health Serv Res. 2006;6:52.

    PubMed  Article  Google Scholar 

  45. 45.

    Reisinger J, Gatterer E, Lang W, Vanicek T, Eisserer G, Bachleitner T, et al. Flecainide versus ibutilide for immediate cardioversion of atrial fibrillation of recent onset. Eur Heart J. 2004;25(15):1318–24.

    PubMed  Article  CAS  Google Scholar 

  46. 46.

    Cropp JS, Antal EG, Talbert RL. Ibutilide: a new class III antiarrhythmic agent. Pharmacotherapy. 1997;17(1):1–9.

    PubMed  CAS  Google Scholar 

  47. 47.

    Tzivoni D, Banai S, Schuger C, Benhorin J, Keren A, Gottlieb S, et al. Treatment of torsade de pointes with magnesium sulfate. Circulation. 1988;77(2):392–7.

    PubMed  Article  CAS  Google Scholar 

  48. 48.

    Coleman CI, Kalus JS, White CM, Spencer AP, Tsikouris JP, Chung JO, et al. Cost effectiveness of ibutilide with prophylactic magnesium in the treatment of atrial fibrillation. Pharmacoeconomics. 2004;22(13):877–83.

    PubMed  Article  CAS  Google Scholar 

  49. 49.

    The Research Group for Antiarrhythmic Drug Therapy. Cost–effectiveness of antiarrhythmic drugs for prevention of thromboembolism in patients with paroxysmal atrial fibrillation. Jpn Circ J. 2001;65(9):765–8.

    Article  Google Scholar 

  50. 50.

    Saborido CM, Hockenhull J, Bagust A, Boland A, Dickson R, Todd D. Systematic review and cost–effectiveness evaluation of “pill-in-the-pocket” strategy for paroxysmal atrial fibrillation compared to episodic in-hospital treatment or continuous antiarrhythmic drug therapy. Health Technol Assess. 2010;14(31):iii–iv, 1–75.

    Google Scholar 

  51. 51.

    Perez A, Touchette DR, DiDomenico RJ, Stamos TD, Walton SM. Comparison of rate control versus rhythm control for management of atrial fibrillation in patients with coexisting heart failure: a cost–effectiveness analysis. Pharmacotherapy. 2011;31(6):552–65.

    PubMed  Article  Google Scholar 

  52. 52.

    Pietrasik A, Kosior DA, Niewada M, Opolski G, Latek M, Kamiñski B. The cost comparison of rhythm and rate control strategies in persistent atrial fibrillation. Int J Cardiol. 2007;118(1):21–7.

    PubMed  Article  Google Scholar 

  53. 53.

    Hagens VE, Vermeulen KM, TenVergert EM, Van Veldhuisen DJ, Bosker HA, Kamp O, et al. Rate control is more cost-effective than rhythm control for patients with persistent atrial fibrillation: results from the RAte Control versus Electrical cardioversion (RACE) study. Eur Heart J. 2004;25(17):1542–9.

    PubMed  Article  Google Scholar 

  54. 54.

    de Paola AAV, Figueiredo E, Sesso R, Veloso HH, Nascimento LOT. Effectiveness and costs of chemical versus electrical cardioversion of atrial fibrillation. Int J Cardiol. 2003;88(2–3):157–66.

    PubMed  Article  Google Scholar 

  55. 55.

    Dunn AB, White CM, Reddy P, Chow MSS, Kluger J. Efficacy and cost analysis of ibutilide. Ann Pharmacother. 2000;34:1233–7.

    PubMed  Article  CAS  Google Scholar 

  56. 56.

    Martin-Doyle W, Reynolds MR. Is AF ablation cost effective? J Atr Fibrillation. 2010;2(1):727–39.

    PubMed  Google Scholar 

  57. 57.

    Rodgers M, McKenna C, Palmer S, Chambers D, Van Hout S, Golder S, et al. Curative catheter ablation in atrial fibrillation and typical atrial flutter: systematic review and economic evaluation. Health Technol Assess. 2008;12(34):iii–iv, xi–xiii, 1–198.

    Google Scholar 

  58. 58.

    McKenna C, Palmer S, Rodgers M, Chambers D, Hawkins N, Golder S, et al. Cost–effectiveness of radiofrequency catheter ablation for the treatment of atrial fibrillation in the United Kingdom. Heart. 2009;95(7):542–9.

    PubMed  Article  CAS  Google Scholar 

  59. 59.

    Reynolds MR, Zimetbaum P, Josephson ME, Ellis E, Danilov T, Cohen DJ. Cost–effectiveness of radiofrequency catheter ablation compared with antiarrhythmic drug therapy for paroxysmal atrial fibrillation. Circ Arrhythm Electrophysiol. 2009;2(4):362–9.

    PubMed  Article  Google Scholar 

  60. 60.

    Kim MH, Klingman D, Lin J, Pathak P, Battleman DS. Cost of hospital admission for antiarrhythmic drug initiation in atrial fibrillation. Ann Pharmacother. 2009;43(5):840–8.

    PubMed  Article  Google Scholar 

  61. 61.

    Jacoby JL, Cesta M, Heller MB, Salen P, Reed J. Synchronized emergency department cardioversion of atrial dysrhythmias saves time, money and resources. J Emerg Med. 2005;28(1):27–30.

    PubMed  Article  Google Scholar 

  62. 62.

    Khaykin Y, Wang X, Natale A, Wazni OM, Skanes AC, Humphries KH, et al. Cost comparison of ablation versus antiarrhythmic drugs as first-line therapy for atrial fibrillation: an economic evaluation of the RAAFT pilot study. J Cardiovasc Electrophysiol. 2009;20(1):7–12.

    PubMed  Article  Google Scholar 

  63. 63.

    Khaykin Y, Morillo CA, Skanes AC, McCracken A, Humphries K, Kerr CR. Cost comparison of catheter ablation and medical therapy in atrial fibrillation. J Cardiovasc Electrophysiol. 2007;18(9):907–13.

    PubMed  Article  Google Scholar 

  64. 64.

    Weerasooriya R, Jaïs P, Le Heuzey J-Y, Scaveé C, Choi K-J, Macle L, et al. Cost analysis of catheter ablation for paroxysmal atrial fibrillation. Pacing Clin Electrophysiol. 2003;26(1 Pt 2):292–4.

    PubMed  Article  Google Scholar 

  65. 65.

    Noro M, Kujime S, Ito N, Enomoto Y, Nakamura K, Sakai T, et al. Cost effectiveness of radiofrequency catheter ablation vs. medical treatment for atrial fibrillation in Japan. Circ J. 2011;75(8):1860–6.

    PubMed  Article  Google Scholar 

  66. 66.

    Brüggenjürgen B, Reinhold T, McBride D, Willich SN. Atrial fibrillation: epidemiologic, economic and individual burden of disease (in German). Deutsche Medizinische Wochenschrift. 2010;135(Suppl 2):S21–5.

    PubMed  Article  Google Scholar 

  67. 67.

    Ramsey S, Willke R, Briggs A, Brown R, Buxton M, Chawla A, et al. Good research practices for cost–effectiveness analysis alongside clinical trials: the ISPOR RCT-CEA Task Force report. Value Health. 2005;8(5):521–33.

    PubMed  Article  Google Scholar 

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No sources of funding were used to prepare this article. The authors have no conflicts of interest that are directly relevant to its content and the opinions expressed are those of the authors. Bernd Brüggenjürgen acts as guarantor for the overall content of this article.

Author Contributions

BB and SW had the idea for the paper. BB, SW and TR designed the study and NE, SK and TR conducted the literature search. BB, NE and SK analysed and interpreted the data. BB, NE and SK drafted the manuscript. All authors reviewed the manuscript and participated in the interpretation of results. All authors have read and approved the final submitted version of the article.

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Correspondence to Bernd Brüggenjürgen.

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Brüggenjürgen, B., Kohler, S., Ezzat, N. et al. Cost Effectiveness of Antiarrhythmic Medications in Patients Suffering from Atrial Fibrillation. PharmacoEconomics 31, 195–213 (2013).

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  • Atrial Fibrillation
  • Amiodarone
  • Catheter Ablation
  • Sotalol
  • Flecainide