Abstract
Purpose
Oral anticoagugulants (OACs) effectively reduce the risk for ischemic stroke in patients with atrial fibrillation (AF), but undertreatment and poor persistence with treatment are important problems. NOACs now provide alternatives to warfarin. This study compares the persistence with presently available antithrombotic treatments in AF patients with a CHA2DS2VASc score ≥2.
Methods
All first claims of either warfarin (n = 9969), dabigatran (n = 2701), rivaroxaban (n = 2074), apixaban (n = 1352), or aspirin (n = 4540) from April 2011 until December 2014, in individuals with non-valvular AF and CHA2DS2VASc scores of 2–9, were identified in the administrative health data register (VAL) of the Stockholm region (2.1 million inhabitants). Prescription claims were analyzed with and without multivariate analysis in relation to age, sex, prescriber category, prior OAC treatment, number of drugs, and death.
Results
The overall persistence with any OAC was 88.2 % (CI 87.5–88.9) at 1 year and 82.9 % (CI 81.8–83.9) at 2 years. After 1 year, the crude persistence was 85.0 % (CI 84.2–85.9) with warfarin, 85.9 % (CI 81.8–90.1) with apixaban, 74.4 % (CI 72.3–76.5) with dabigatran, and 77.4 % (CI 74.6–80.2) with rivaroxaban. Multivariate analysis confirmed significantly higher persistence with warfarin and apixaban than with dabigatran or rivaroxaban. The adherence (proportion of days covered >80 %) was above 90 % for all NOACs; significantly higher with rivaroxaban compared to dabigatran (p < 0.001), but not compared to apixaban (p = 0.14).
Conclusions
After 2 years, the persistence with any anticoagulant treatment was high in patients with non-valvular AF. Our results indicate better persistence with warfarin and apixaban than with dabigatran or rivaroxaban in regular care.
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References
Friberg L, Bergfeldt L (2013) Atrial fibrillation prevalence revisited. Intern Med 274:461–468
Forslund T, Wettermark B, Wändell P, von Euler M, Hasselström J, Hjemdahl P (2014) Risks for stroke and bleeding with warfarin or aspirin treatment in patients with atrial fibrillation at different CHA(2)DS(2)VASc scores: experience from the Stockholm region. Eur J Clin Pharmacol 70:1477–1485
Hart RG, Pearce LA, Aguilar MI (2007) Meta-analysis: antithrombotic therapy to prevent stroke in patients who have nonvalvular atrial fibrillation. Ann Intern Med 146:857–867
Connolly SJ, Ezekowitz MD, Yusuf S, et al. (2009) (For the RE-LY investigators): dabigatran versus warfarin in patients with atrial fibrillation. N Engl J Med 361:1139–1151
Patel MR, Mahaffey KW, Garg J, et al. (2011) Rivaroxaban versus Warfarin in Nonvalvular Atrial Fibrillation. N Engl J Med 8(365):883–891
Granger CB, Alexander JH, McMurray JJ, et al. (2011) Apixaban versus warfarin in patients with atrial fibrillation. N Engl J Med 365:981–992
Forslund T, Wettermark B, Wändell P, von Euler M, Hasselström J, Hjemdahl P (2013) Risk scoring and thromboprophylactic treatment of patients with atrial fibrillation with and without access to primary healthcare data: experience from the Stockholm health care system. Int J Cardiol 170:208–214
Camm AJ, Lip GY (2012) De Caterina R, Savelieva I, Atar D, Hohnloser SH, Hindricks G, Kirchhof P; ESC Committee for Practice Guidelines (CPG); 2012 focused update of the ESC Guidelines for the management of atrial fibrillation: an update of the 2010 ESC Guidelines for the management of atrial fibrillation. Developed with the special contribution of the European Heart Rhythm Association. Eur Heart J 33:2719–2747
Chatterjee S, Sardar P, Giri JS, Ghosh J, Mukherjee D (2014) Treatment discontinuations with new oral agents for long-term anticoagulation: insights from a meta-analysis of 18 randomized trials including 101,801 patients. Mayo Clin Proc 89:896–907
Granger CB, Alexander JH, McMurray JJ, Lopes RD, Hylek EM, Hanna M, Al-Khalidi HR, Ansell J, Atar D, Avezum A, Bahit MC, Diaz R, Easton JD, Ezekowitz JA, Flaker G, Garcia D, Geraldes M, Gersh BJ, Golitsyn S, Goto S, Hermosillo AG, Hohnloser SH, Horowitz J, Mohan P, Jansky P, Lewis BS, Lopez-Sendon JL, Pais P, Parkhomenko A, Verheugt FW, Zhu J, Wallentin L, ARISTOTLE Committees and Investigators (2011) Apixaban in patients with atrial fibrillation. N Engl J Med 364:806–817
Eichler HG, Abadie E, Breckenridge A, et al. (2011) Bridging the efficacy-effectiveness gap: a regulator’s perspective on addressing variability of drug response. Nat Review Drug Discov. 10:495–506
Skeppholm M, Friberg L (2014) Adherence to warfarin treatment among patients with atrial fibrillation. Clin Res Cardiol 103:998–1005
Lip GY, Laroche C, Ioachim PM, Rasmussen LH, Vitali-Serdoz L, Petrescu L, Darabantiu D, Crijns HJ, Kirchhof P, Vardas P, Tavazzi L, Maggioni AP, Boriani G (2014) Prognosis and treatment of atrial fibrillation patients by European cardiologists: one year follow-up of the EURObservational Research Programme-Atrial Fibrillation General Registry Pilot Phase (EORP-AF Pilot registry). Eur Heart J 35:3365–3376
Song X, Sander SD, Varker H, Amin A (2012) Patterns and predictors of use of warfarin and other common long-term medications in patients with atrial fibrillation. Am J Cardiovasc Drugs 12:245–253
Gallagher AM, Rietbrock S, Plumb J, van Staa TP (2008) Initiation and persistence of warfarin or aspirin in patients with chronic atrial fibrillation in general practice: do the appropriate patients receive stroke prophylaxis? J Thromb Haemost 6:1500–1506
Suh DC, Choi JC, Schein J, Kim S, Nelson WW (2013) Factors associated with warfarin discontinuation, including bleeding patterns, in atrial fibrillation patients. Curr Med Res Opin 29:761–771
Zalesak M, Siu K, Francis K, Yu C, Alvrtsyan H, Rao Y, Walker D, Sander S, Miyasato G, Matchar D, Sanchez H (2013) Higher persistence in newly diagnosed nonvalvular atrial fibrillation patients treated with dabigatran versus warfarin. Circ Cardiovasc Qual Outcomes 6:567–574
Beyer-Westendorf J, Ebertz F, Förster K, Gelbricht V, Michalski F, Köhler C, Werth S, Endig H, Pannach S, Tittl L, Sahin K, Daschkow K, Weiss N (2015) Effectiveness and safety of dabigatran therapy in daily-care patients with atrial fibrillation. Results from the Dresden NOAC registry. Thromb Haemost 113:1247–1257
Shore S, Carey EP, Turakhia MP, Jackevicius CA, Cunningham F, Pilote L, Bradley SM, Maddox TM, Grunwald GK, Barón AE, Rumsfeld JS, Varosy PD, Schneider PM, Marzec LN, Ho PM (2014) Adherence to dabigatran therapy and longitudinal patient outcomes: insights from the Veterans health administration. Am Heart J 167:810–817
Shore S, Ho PM, Lambert-Kerzner A, Glorioso TJ, Carey EP, Cunningham F, Longo L, Jackevicius C, Rose A, Turakhia MP (2015) Site-level variation in and practices associated with dabigatran adherence. J Am Med Assoc 313:1443–1450
Beyer-Westendorf J, Förster K, Ebertz F, Gelbricht V, Schreier T, Göbelt M, Michalski F, Endig H, Sahin K, Tittl L, Weiss N (2015) Drug persistence with rivaroxaban therapy in atrial fibrillation patients-results from the Dresden non-interventional oral anticoagulation registry. Europace 17:530–538
Nelson WW, Song X, Coleman CI, Thomson E, Smith DM, Damaraju CV, Schein JR (2014) Medication persistence and discontinuation of rivaroxaban versus warfarin among patients with non-valvular atrial fibrillation. Curr Med Res Opin 30:2461–2469
Laliberté F, Cloutier M, Nelson WW, Coleman CI, Pilon D, Olson WH, Damaraju CV, Schein JR, Lefebvre P (2014) Real-world comparative effectiveness and safety of rivaroxaban and warfarin in nonvalvular atrial fibrillation patients. Curr Med Res Opin 30:1317–1325
Caetano PA, Lam JM, Morgan SG (2006) Toward a standard definition and measurement of persistence with drug therapy: examples from research on statin and antihypertensive utilization. Clin Ther 28:1411–1424
Raebel MA, Schmittdiel J, Karter AJ, Konieczny JL, Steiner JF (2013) Standardizing terminology and definitions of medication adherence and persistence in research employing electronic databases. Med Care 51:S11–S21
Friberg L, Skeppholm M, Terént A (2015) Benefit of anticoagulation unlikely in patients with atrial fibrillation and a CHA2DS2-VASc score of 1. J Am Coll Cardiol 65:225–232
Wettermark B, Hammar N, Fored M, Leimanis A, Otterblad Olausson P, Bergman U, Persson I, Sundström A, Westerholm B, Rosén M (2007) The new Swedish prescribed drug register—opportunities for pharmacoepidemiological research and experience from the first six months. Pharmacoepidemiol Drug Saf 16:726–735
January CT, Wann LS, Alpert JS, Calkins H, Cleveland Jr JC, Cigarroa JE, Conti JB, Ellinor PT, Ezekowitz MD, Field ME, Murray KT, Sacco RL, Stevenson WG, Tchou PJ, Tracy CM, Yancy CW (2014) 2014 AHA/ACC/HRS guideline for the management of patients with atrial fibrillation: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the Heart Rhythm Society. Circ 130:2071–2104
Ben Freedman S, Gersh BJ, Lip GY (2015) Misperceptions of aspirin efficacy and safety may perpetuate anticoagulant underutilization in atrial fibrillation. Eur Heart J 36:653–656
Sjögren V, Grzymala-Lubanski B, Renlund H, Friberg L, Lip GY, Svensson PJ, Själander A (2015) Safety and efficacy of well managed warfarin. A report from the Swedish quality register auricula. Thromb Haemost 113:1370–1377
Singer DE, Hellkamp AS, Piccini JP, Mahaffey KW, Lokhnygina Y, Pan G, Halperin JL, Becker RC, Breithardt G, Hankey GJ, Hacke W, Nessel CC, Patel MR, Califf RM (2013) Fox KA; ROCKET AF investigators. Impact of global geographic region on time in therapeutic range on warfarin anticoagulant therapy: data from the ROCKET AF clinical trial. J Am Heart Assoc 2:e000067
Saini SD, Schoenfeld P, Kaulback K, Dubinsky MC (2009) Effect of medication dosing frequency on adherence in chronic diseases. Am J Manag Care. 15:e22–e33
Vrijens B, Heidbuchel H (2015) Non-vitamin K antagonist oral anticoagulants: considerations on once- vs. twice-daily regimens and their potential impact on medication adherence. Europace 17:514–523
Ludvigsson JF, Andersson E, Ekbom A, Feychting M, Kim JL, Reuterwall C, Heurgren M, Olausson PO (2011) External review and validation of the Swedish national inpatient register. BMC Public Health 11:450
Schneeweiss S, Gagne JJ, Glynn RJ, Ruhl M, Rassen JA (2011) Assessing the comparative effectiveness of newly marketed medications: methodological challenges and implications for drug development. Clin Pharmacol Ther 90:777–790
Acknowledgments
Per Näsman (PhD, Royal Institute of Technology, Stockholm, Sweden) for statistical advice.
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Funding was provided from the Stockholm County Council.
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Forslund, T., Wettermark, B. & Hjemdahl, P. Comparison of treatment persistence with different oral anticoagulants in patients with atrial fibrillation. Eur J Clin Pharmacol 72, 329–338 (2016). https://doi.org/10.1007/s00228-015-1983-z
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DOI: https://doi.org/10.1007/s00228-015-1983-z