Subscribe to RSS
Therapy persistence in newly diagnosed non-valvular atrial fibrillation treated with warfarin or NOACA cohort study
28 April 2015
Accepted after minor revision: 23 June 2015
22 November 2017 (online)
Efforts to reduce stroke in atrial fibrillation (AF) have focused on increasing physician adherence to oral anticoagulant (OAC) guidelines, but high early vitamin K antagonist (VKA) discontinuation is a limitation. We compared persistence of non-VKA OAC (NOAC) with VKA treatment in the first year after OAC inception for incident AF in real-world practice. We studied 27,514 anticoagulant-naïve patients with incident non-valvular AF between January 2011 and May 2014 in the UK primary care Clinical Practice Research Datalink, with full medication use linkage: mean age 74.2 ± 12.4, 45.7 % female, mean follow-up 1.9 ± 1.1 years. After treatment initiation and follow-up until 1/2015, the proportion remaining on OAC at one year (persistence) was estimated using competing risk survival analyses. OAC was commenced ≤90 days after incident AF in 13,221 patients (48.1 %): 12,307 VKA and 914 NOAC (apixaban, dabigatran, rivaroxaban). Amongst those treated with OAC, the proportion commencing NOAC increased from zero in 1/2011 to 27.0 % in 5/2014, and OAC prescriptions for CHA2DS2VASc score ≥2 (guideline adherence) increased from 41.2 % to 65.5 %. Persistence with OAC declined over 12 months to 63.6 % for VKA and 79.2 % for NOAC (p< 0.0001). Persistence for those with CHA2DS2VASc ≥2 was significantly greater for NOAC (83.0 %) than VKA (65.3 %, p< 0.0001) at one year and all earlier time points. Comparison of VKA and NOAC cohorts matched on individual CHA2DS2VASc components showed consistent results. In conclusion, persistence was significantly higher with NOAC than VKA, and could alone lead to fewer cardioembolic strokes. Increased guideline adherence following NOAC introduction could further decrease AF stroke burden.
Supplementary Material to this article is available online at www.thrombosis-online.com.
- 1 Hart RG, Pearce LA, Aguilar MI. Meta-analysis: antithrombotic therapy to prevent stroke in patients who have nonvalvular atrial fibrillation. Ann Intern Med 2007; 146: 857-867.
- 2 Camm AJ, Lip GYH, Caterina RD. et al. 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 2012; 33: 2719-2747.
- 3 January CT, Wann LS, Alpert JS. et al. 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. J Am Coll Cardiol. 2014 Epub ahead of print.
- 4 Connolly SJ, Ezekowitz MD, Yusuf S. et al. Dabigatran versus warfarin in patients with atrial fibrillation. N Engl J Med 2009; 361: 1139-1151.
- 5 Ruff CT, Giugliano RP, Braunwald E. et al. Comparison of the efficacy and safety of new oral anticoagulants with warfarin in patients with atrial fibrillation: a meta-analysis of randomised trials. Lancet 2014; 383: 955-962.
- 6 Nieuwlaat R, Capucci A, Lip GY. et al. Antithrombotic treatment in real-life atrial fibrillation patients: a report from the Euro Heart Survey on Atrial Fibrillation. Eur Heart J 2006; 27: 3018-3026.
- 7 Martinez C, Katholing A, Freedman SB. Adverse prognosis of incidentally detected ambulatory atrial fibrillation. A cohort study. Thromb Haemost 2014; 112: 276-286.
- 8 Kakkar AK, Mueller I, Bassand JP. et al. Risk profiles and antithrombotic treatment of patients newly diagnosed with atrial fibrillation at risk of stroke: perspectives from the international, observational, prospective GARFIELD registry. PloS one 2013; 08: e63479.
- 9 Lowres N, Neubeck L, Salkeld G. et al. Feasibility and cost effectiveness of stroke prevention through community screening for atrial fibrillation using iPhone ECG in pharmacies. The SEARCH-AF study. Thromb Haemost 2014; 111: 1167-1176.
- 10 Nieuwlaat R, Olsson SB, Lip GY. et al. Guideline-adherent antithrombotic treatment is associated with improved outcomes compared with undertreatment in high-risk patients with atrial fibrillation. The Euro Heart Survey on Atrial Fibrillation. Am Heart J 2007; 153: 1006-1012.
- 11 White HD, Gruber M, Feyzi J. et al. Comparison of outcomes among patients randomized to warfarin therapy according to anticoagulant control: results from SPORTIF III and V. Arch Internal Med 2007; 167: 239-245.
- 12 Gallagher AM, Setakis E, Plumb JM. et al. Risks of stroke and mortality associated with suboptimal anticoagulation in atrial fibrillation patients. Thromb Haemost 2011; 106: 968-977.
- 13 Kimmel SE, Chen Z, Price M. et al. The influence of patient adherence on anticoagulation control with warfarin: results from the International Normalized Ratio Adherence and Genetics (IN-RANGE) Study. Arch Intern Med 2007; 167: 229-235.
- 14 Hylek EM, Evans-Molina C, Shea C. et al. Major hemorrhage and tolerability of warfarin in the first year of therapy among elderly patients with atrial fibrillation. Circulation 2007; 115: 2689-2696.
- 15 Gallagher AM, Rietbrock S, Plumb J. et al. 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 2008; 06: 1500-1506.
- 16 Song X, Sander SD, Varker H. et al. Patterns and predictors of use of warfarin and other common long-term medications in patients with atrial fibrillation. Am J Cardiovasc Drugs 2012; 12: 245-253.
- 17 Fitch K, Broulette J, Pyenson B. et al. Erratum: utilization of anticoagulation therapy in medicare patients with nonvalvular atrial fibrillation. Am Health Drug Benef 2012; 05: 157-168.
- 18 Giugliano RP, Ruff CT, Braunwald E. et al. Edoxaban versus Warfarin in Patients with Atrial Fibrillation. N Engl J Med 2013; 369: 2093-2104.
- 19 Tsai K, Erickson SC, Yang J. et al. Adherence, persistence, and switching patterns of dabigatran etexilate. Am J Manag Care 2013; 19: e325-332.
- 20 Michel J, Mundell D, Boga T. et al. Dabigatran for anticoagulation in atrial fibrillation – early clinical experience in a hospital population and comparison to trial data. Heart Lung Circ 2013; 22: 50-55.
- 21 Zalesak M, Siu K, Francis K. et al. Higher persistence in newly diagnosed nonvalvular atrial fibrillation patients treated with dabigatran versus warfarin. Circ Cardiovasc Qual Outcomes 2013; 06: 567-574.
- 22 Shore S, Carey EP, Turakhia MP. et al. Adherence to dabigatran therapy and longitudinal patient outcomes: insights from the veterans health administration. Am Heart J 2014; 167: 810-817.
- 23 Laliberte F, Cloutier M, Nelson WW. et al. Real-world comparative effectiveness and safety of rivaroxaban and warfarin in nonvalvular atrial fibrillation patients. Curr Med Res Opin 2014; 30: 1317-1325.
- 24 Nelson WW, Song X, Coleman CI. et al. Medication persistence and discontinuation of rivaroxaban versus warfarin among patients with non-valvular atrial fibrillation. Curr Med Res Opin 2014; 30: 2461-2469.
- 25 Khan NF, Perera R, Harper S. et al. Adaptation and validation of the Charlson Index for Read/OXMIS coded databases. BMC Fam Pract 2010; 11: 1.
- 26 Satagopan JM, Ben-Porat L, Berwick M. et al. A note on competing risks in survival data analysis. Br J Cancer 2004; 91: 1229-1235.
- 27 Gray RJ. A class of K–sample tests for comparing the cumulative incidence of a competing risk. Ann Stat 1988; 16: 1141-1154.
- 28 Jones C, Pollit V, Fitzmaurice D. et al. The management of atrial fibrillation: summary of updated NICE guidance. Br Med J 2014; 348: g3655.
- 29 Freedman SB, Gersh BJ, Lip GY. Misperceptions of aspirin efficacy and safety may perpetuate anticoagulant underutilization in atrial fibrillation. Eur Heart J 2015; 36: 653-656.
- 30 Gomes T, Mamdani MM, Holbrook AM. et al. Persistence with therapy among patients treated with warfarin for atrial fibrillation. Arch Intern Med 2012; 172: 1687-1689.
- 31 Mant J, Hobbs FD, Fletcher K. et al. Warfarin versus aspirin for stroke prevention in an elderly community population with atrial fibrillation (the Birmingham Atrial Fibrillation Treatment of the Aged Study, BAFTA): a randomised controlled trial. Lancet 2007; 370: 493-503.
- 32 De Schryver EL, van Gijn J, Kappelle LJ. et al. Non-adherence to aspirin or oral anticoagulants in secondary prevention after ischaemic stroke. J Neurol 2005; 252: 1316-1321.
- 33 Fang MC, Go AS, Chang Y. et al. Warfarin discontinuation after starting warfarin for atrial fibrillation. Circ Cardiovasc Qual Outcomes 2010; 03: 624-631.
- 34 Simons LA, Ortiz M, Germanos P. et al. Persistence on warfarin in patients with atrial fibrillation: experience in Australia 2006–2009. Austral Fam Phys 2013; 42: 659-661.
- 35 Patel MR, Mahaffey KW, Garg J. et al. Rivaroxaban versus warfarin in nonvalvular atrial fibrillation. N Engl J Med 2011; 365: 883-891.
- 36 Granger CB, Alexander JH, McMurray JJ. et al. Apixaban versus warfarin in patients with atrial fibrillation. N Engl J Med 2011; 365: 981-992.
- 37 Hylek EM, Ko D, Cove CL. Gaps in translation from trials to practice: non-vitamin K antagonist oral anticoagulants (NOACs) for stroke prevention in atrial fibrillation. Thromb Haemost 2014; 111: 783-788.
- 38 Beyer-Westendorf J, Ebertz F, Forster K. et al. Effectiveness and safety of dabigatran therapy in daily-care patients with atrial fibrillation. Results from the Dresden NOAC Registry. Thromb Haemost 2015; 113: 1247-1257.
- 39 Beyer-Westendorf J, Forster K, Ebertz F. et al. Drug persistence with rivaroxaban therapy in atrial fibrillation patients-results from the Dresden non-interventional oral anticoagulation registry. Europace 2015; 17: 530-538.
- 40 Lip GY, Laroche C, Ioachim PM. et al. 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 2014; 35: 3365-3376.
- 41 Gorst-Rasmussen A, Skjoth F, Larsen TB. et al. Dabigatran adherence in atrial fibrillation patients during the first year after diagnosis: a nationwide cohort study. J Thromb Haemost. 2015 Epub ahead of print.
- 42 Lane DA, Lip GY. Patient’s values and preferences for stroke prevention in atrial fibrillation: balancing stroke and bleeding risk with oral anticoagulation. Thromb Haemost 2014; 111: 381-383.
- 43 Lahaye S, Regpala S, Lacombe S. et al. Evaluation of patients’ attitudes towards stroke prevention and bleeding risk in atrial fibrillation. Thromb Haemost 2014; 111: 465-473.
- 44 Le Heuzey JY, Ammentorp B, Darius H. et al. Differences among western European countries in anticoagulation management of atrial fibrillation. Data from the PREFER IN AF registry. Thromb Haemost 2014; 111: 833-841.