Direct Oral Anticoagulants for the Management of Thromboembolic Disorders: The Importance of Adherence and Persistence in Achieving Beneficial Outcomes

Clinical and Applied Thrombosis/Hemostasis

Volumn 22, Issue 7, 2016, Pages 605-616

  Amin, Alpesh ^a   Marrs, Joel C ^b  

^a UNIVERSITY OF CALIFORNIA   (United States)

^b UNIVERSITY OF COLORADO   (United States)

Author keywords

adherence; atrial fibrillation; direct oral anticoagulant; dosing regimen; persistence; stroke; venous thromboembolism

Indexed keywords

APIXABAN; BLOOD CLOTTING FACTOR 10A; BLOOD CLOTTING FACTOR 10A INHIBITOR; DABIGATRAN; EDOXABAN; RIVAROXABAN; ANTICOAGULANT AGENT;

ANTICOAGULANT THERAPY; ARTICLE; ATRIAL FIBRILLATION; CLINICAL PRACTICE; DOSE CALCULATION; DRUG ADMINISTRATION ROUTE; DRUG EFFICACY; DRUG SAFETY; HUMAN; MEDICATION COMPLIANCE; META ANALYSIS (TOPIC); PATIENT COMPLIANCE; PHASE 2 CLINICAL TRIAL (TOPIC); PHASE 3 CLINICAL TRIAL (TOPIC); PRIORITY JOURNAL; RANDOMIZED CONTROLLED TRIAL (TOPIC); TREATMENT OUTCOME; VENOUS THROMBOEMBOLISM; ORAL DRUG ADMINISTRATION; STROKE; THROMBOEMBOLISM;

ADMINISTRATION, ORAL; ANTICOAGULANTS; ATRIAL FIBRILLATION; HUMANS; STROKE; THROMBOEMBOLISM; TREATMENT OUTCOME; VENOUS THROMBOEMBOLISM;

EID: 84984907236     PISSN: 10760296     EISSN: 19382723     Source Type: Journal    
DOI: 10.1177/1076029615601492     Document Type: Article

References (96)

1. Piccini JP, Hammill BG, Sinner MF, et al. Incidence and prevalence of atrial fibrillation and associated mortality among Medicare beneficiaries, 1993-2007. Circ Cardiovasc Qual Outcomes. 2012; 5 (1): 85-93.
2. Manolis AJ, Rosei EA, Coca A, et al. Hypertension and atrial fibrillation: diagnostic approach, prevention and treatment. Position paper of the Working Group 'Hypertension Arrhythmias and Thrombosis' of the European Society of Hypertension. J Hypertens. 2012; 30 (2): 239-252.
3. Lau CP,. Pacing for atrial fibrillation. Heart. 2003; 89 (1): 106-112.
4. Liu X, Phatak H, Dillon R, Mitchell S,. Epidemiology and mortality of venous thromboembolism across patient populations: a systematic literature review. Value Health. 2013; 16 (3): A272. Abstract PCV5.
5. Anderson FA Jr, Spencer FA,. Risk factors for venous thromboembolism. Circulation. 2003; 107 (23 suppl 1): I9-I16.
6. McRae SJ, Ginsberg JS,. Initial treatment of venous thromboembolism. Circulation. 2004; 110 (9 suppl 1): I3-I9.
7. Fanikos J, Piazza G, Zayaruzny M, Goldhaber SZ,. Long-term complications of medical patients with hospital-acquired venous thromboembolism. Thromb Haemost. 2009; 102 (4): 688-693.
8. Cohen AT,. Long-term benefits of preventing venous thromboembolic events. Curr Med Res Opin. 2012; 28 (6): 877-889.
9. Prandoni P,. Prevention and treatment of venous thromboembolism with low-molecular-weight heparins: clinical implications of the recent European guidelines. Thromb J. 2008; 6: 13.
10. Wells P, Anderson D,. The diagnosis and treatment of venous thromboembolism. Hematology Am Soc Hematol Educ Program. 2013; 2013: 457-463.
11. Vazquez SR, Freeman A, VanWoerkom RC, Rondina MT,. Contemporary issues in the prevention and management of postthrombotic syndrome. Ann Pharmacother. 2009; 43 (11): 1824-1835.
12. Lang IM, Pesavento R, Bonderman D, Yuan JX,. Risk factors and basic mechanisms of chronic thromboembolic pulmonary hypertension: a current understanding. Eur Respir J. 2013; 41 (2): 462-468.
13. Zhu T, Martinez I, Emmerich J,. Venous thromboembolism: risk factors for recurrence. Arterioscler Thromb Vasc Biol. 2009; 29 (3): 298-310.
14. Miyasaka Y, Barnes ME, Gersh BJ, et al. Secular trends in incidence of atrial fibrillation in Olmsted County, Minnesota, 1980 to 2000, and implications on the projections for future prevalence. Circulation. 2006; 114 (2): 119-125.
15. Deitelzweig SB, Johnson BH, Lin J, Schulman KL,. Prevalence of clinical venous thromboembolism in the USA: Current trends and future projections. Am J Hematol. 2011; 86 (2): 217-220.
16. White RH,. The epidemiology of venous thromboembolism. Circulation. 2003; 107 (23 suppl 1): 14-18.
17. 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): 1534-1539.
18. Goldhaber SZ, Morrison RB,. Cardiology patient pages. Pulmonary embolism and deep vein thrombosis. Circulation. 2002; 106 (12): 1436-1438.
19. Key NS, Kasthuri RS,. Current treatment of venous thromboembolism. Arterioscler Thromb Vasc Biol. 2010; 30 (3): 372-375.
20. Kearon C, Akl EA, Comerota AJ, et al. Antithrombotic therapy for VTE disease: antithrombotic therapy and prevention of thrombosis, 9th ed: American College of Chest Physicians evidence-based clinical practice guidelines. Chest. 2012; 141 (2 suppl): e419S-e494S.
21. Eikelboom JW, Weitz JI,. New anticoagulants. Circulation. 2010; 121 (13): 1523-1532.
22. Garcia D, Ageno W, Libby E,. Update on the diagnosis and management of pulmonary embolism. Br J Haematol. 2005; 131 (3): 301-312.
23. ® Summary of Product Characteristics. 2014. Published June 20, 2011. Web site. http://www.ema.europa.eu/docs/en-GB/document-library/EPAR-Product-Information/human/002148/WC500107728.pdf. Accessed May 4, 2015.
24. ® Summary of Product Characteristics. 2015. Published December 15, 2009. Web site. http://www.ema.europa.eu/docs/en-GB/document-library/EPAR-Product-Information/human/000829/WC500041059.pdf. Accessed February 8, 2015.
25. ® Summary of Product Characteristics. 2015. Published December 1, 2009. Web site. http://www.ema.europa.eu/docs/en-GB/document-library/EPAR-Product-Information/human/000944/WC500057108.pdf. Accessed July 17, 2015.
26. The EINSTEIN Investigators. Oral rivaroxaban for symptomatic venous thromboembolism. N Engl J Med. 2010; 363 (26): 2499-2510.
27. The EINSTEIN-PE Investigators. Oral rivaroxaban for the treatment of symptomatic pulmonary embolism. N Engl J Med. 2012; 366 (14): 1287-1297.
28. Prins MH, Lensing AWA, Bauersachs R, et al. Oral rivaroxaban versus standard therapy for the treatment of symptomatic venous thromboembolism: a pooled analysis of the EINSTEIN-DVT and PE randomized studies. Thromb J. 2013; 11 (1): 21.
29. Agnelli G, Buller HR, Cohen A, et al. Oral apixaban for the treatment of acute venous thromboembolism. N Engl J Med. 2013; 369 (9): 799-808.
30. Connolly SJ, Ezekowitz MD, Yusuf S, et al. Dabigatran versus warfarin in patients with atrial fibrillation. N Engl J Med. 2009; 361 (12): 1139-1151.
31. Patel MR, Mahaffey KW, Garg J, et al. Rivaroxaban versus warfarin in nonvalvular atrial fibrillation. N Engl J Med. 2011; 365 (10): 883-891.
32. Schulman S, Kearon C, Kakkar AK, et al. Dabigatran versus warfarin in the treatment of acute venous thromboembolism. N Engl J Med. 2009; 361 (24): 2342-2352.
33. Schulman S, Kakkar AK, Goldhaber SZ, et al. Treatment of acute venous thromboembolism with dabigatran or warfarin and pooled analysis. Circulation. 2014; 129 (7): 764-772.
34. Granger CB, Alexander JH, McMurray JJ, et al. Apixaban versus warfarin in patients with atrial fibrillation. N Engl J Med. 2011; 365 (11): 981-992.
35. Giugliano RP, Ruff CT, Braunwald E, et al. Edoxaban versus warfarin in patients with atrial fibrillation. N Engl J Med. 2013; 369 (22): 2093-2104.
36. The Hokusai-VTE Investigators. Edoxaban versus warfarin for the treatment of symptomatic venous thromboembolism. N Engl J Med. 2013; 369 (15): 1406-1415.
37. Garcia D, Libby E, Crowther MA,. The new oral anticoagulants. Blood. 2010; 115 (1): 15-20.
38. Agnelli G, Buller HR, Cohen A, et al. Apixaban for extended treatment of venous thromboembolism. N Engl J Med. 2013; 368 (8): 699-708.
39. Schulman S, Kearon C, Kakkar AK, et al. Extended use of dabigatran, warfarin, or placebo in venous thromboembolism. N Engl J Med. 2013; 368 (8): 709-718.
40. Agnelli G, Gallus A, Goldhaber SZ, et al. Treatment of proximal deep-vein thrombosis with the oral direct Factor Xa inhibitor rivaroxaban (BAY 59-7939): the ODIXa-DVT (Oral Direct Factor Xa Inhibitor BAY 59-7939 in patients with acute symptomatic Deep-Vein Thrombosis) study. Circulation. 2007; 116 (2): 180-187.
41. Heit JA, Mohr DN, Silverstein MD, Petterson TM, O'Fallon WM, Melton LJ III,. Predictors of recurrence after deep vein thrombosis and pulmonary embolism: a population-based cohort study. Arch Intern Med. 2000; 160 (6): 761-768.
42. Kearon C, Gent M, Hirsh J, et al. A comparison of three months of anticoagulation with extended anticoagulation for a first episode of idiopathic venous thromboembolism. N Engl J Med. 1999; 340 (12): 901-907.
43. Buller HR, Lensing AWA, Prins MH, et al. A dose-ranging study evaluating once-daily oral administration of the Factor Xa inhibitor rivaroxaban in the treatment of patients with acute symptomatic deep vein thrombosis: the Einstein-DVT Dose-Ranging Study. Blood. 2008; 112 (6): 2242-2247.
44. Botticelli Investigators, Buller H, Deitchman D, Prins M, Segers A,. Efficacy and safety of the oral direct factor Xa inhibitor apixaban for symptomatic deep-vein thrombosis. The Botticelli DVT dose-ranging study. J Thromb Haemost. 2008; 6 (8): 1313-1318.
45. Tendera M, Syzdól M, Parma Z,. ARISTOTLE RE-LYs on the ROCKET. What's new in stroke prevention in patients with atrial fibrillation? Cardiol J. 2012; 19 (1): 4-10.
46. Camm AJ, Lip GYH, De Caterina R, 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 (21): 2719-2747.
47. Ezekowitz MD, Reilly P, Nehmiz G, et al. Dabigatran with or without concomitant aspirin compared with warfarin alone in patients with nonvalvular atrial fibrillation (PETRO Study). Am J Cardiol. 2007; 100 (9): 1419-1426.
48. Renda G, De Caterina R,. The new oral anticoagulants in atrial fibrillation: Once daily or twice daily? Vascul Pharmacol. 2013; 59 (3-4): 53-62.
49. Mueck W, Lensing AWA, Agnelli G, Décousus H, Prandoni P, Misselwitz F,. Rivaroxaban: population pharmacokinetic analyses in patients treated for acute deep-vein thrombosis and exposure simulations in patients with atrial fibrillation treated for stroke prevention. Clin Pharmacokinet. 2011; 50 (10): 675-686.
50. Connolly SJ, Ezekowitz MD, Yusuf S, Reilly PA, Wallentin L,. Newly identified events in the RE-LY trial. N Engl J Med. 2010; 363 (19): 1875-1876.
51. Connolly SJ, Wallentin L, Yusuf S,. Additional events in the RE-LY trial. N Engl J Med. 2014; 371 (15): 1464-1465.
52. Eikelboom JW, Wallentin L, Connolly SJ, et al. Risk of bleeding with 2 doses of dabigatran compared with warfarin in older and younger patients with atrial fibrillation: an analysis of the randomized evaluation of long-term anticoagulant therapy (RE-LY) trial. Circulation. 2011; 123 (21): 2363-2372.
53. Piccini JP, Hellkamp AS, Lokhnygina Y, et al. Relationship between time in therapeutic range and comparative treatment effect of rivaroxaban and warfarin: results from the ROCKET AF trial. J Am Heart Assoc. 2014; 3 (2): e000521.
54. Wallentin L, Yusuf S, Ezekowitz MD, et al. Efficacy and safety of dabigatran compared with warfarin at different levels of international normalised ratio control for stroke prevention in atrial fibrillation: an analysis of the RE-LY trial. Lancet. 2010; 376 (9745): 975-983.
55. Wallentin L, Lopes RD, Hanna M, et al. Efficacy and safety of apixaban compared with warfarin at different levels of predicted international normalized ratio control for stroke prevention in atrial fibrillation. Circulation. 2013; 127 (22): 2166-2176.
56. Vrijens B, De Geest S, Hughes DA, et al. A new taxonomy for describing and defining adherence to medications. Br J Clin Pharmacol. 2012; 73 (5): 691-705.
57. Cramer JA, Roy A, Burrell A, et al. Medication compliance and persistence: terminology and definitions. Value Health. 2008; 11 (1): 44-47.
58. Ho PM, Bryson CL, Rumsfeld JS,. Medication adherence: its importance in cardiovascular outcomes. Circulation. 2009; 119 (23): 3028-3035.
59. Heidbuchel H, Verhamme P, Alings M, et al. European Heart Rhythm Association Practical Guide on the use of new oral anticoagulants in patients with non-valvular atrial fibrillation. Europace. 2013; 15 (5): 625-651.
60. Jin J, Sklar GE, Min SOV, Chuen LS,. Factors affecting therapeutic compliance: a review from the patient's perspective. Ther Clin Risk Manag. 2008; 4 (1): 269-286.
61. 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 (3): 229-235.
62. Laliberté 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 (7): 1317-1325.
63. 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 (12): 2461-2469.
64. 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; 6 (5): 567-574.
65. Coleman CI, Roberts MS, Sobieraj DM, Lee S, Alam T, Kaur R,. Effect of dosing frequency on chronic cardiovascular disease medication adherence. Curr Med Res Opin. 2012; 28 (5): 669-680.
66. Bae JP, Dobesh PP, Klepser DG, et al. Adherence and dosing frequency of common medications for cardiovascular patients. Am J Manag Care. 2012; 18 (3): 139-146.
67. Srivastava K, Arora A, Kataria A, Cappelleri JC, Sadosky A, Peterson AM,. Impact of reducing dosing frequency on adherence to oral therapies: a literature review and meta-analysis. Patient Prefer Adherence. 2013; 7: 419-434.
68. Belsey JD,. Optimizing adherence in hypertension: a comparison of outcomes and costs using single tablet regimens vs individual component regimens. J Med Econ. 2012; 15 (5): 897-905.
69. Shi L, Hodges M, Yurgin N, Boye KS,. Impact of dose frequency on compliance and health outcomes: a literature review (1966-2006). Expert Rev Pharmacoecon Outcomes Res. 2007; 7 (2): 187-202.
70. Claxton AJ, Cramer J, Pierce C,. A systematic review of the associations between dose regimens and medication compliance. Clin Ther. 2001; 23 (8): 1296-1310.
71. Iskedjian M, Einarson TR, MacKeigan LD, et al. Relationship between daily dose frequency and adherence to antihypertensive pharmacotherapy: evidence from a meta-analysis. Clin Ther. 2002; 24 (2): 302-316.
72. Parienti JJ, Bangsberg DR, Verdon R, Gardner EM,. Better adherence with once-daily antiretroviral regimens: a meta-analysis. Clin Infect Dis. 2009; 48 (4): 484-488.
73. Coleman CI, Limone B, Sobieraj DM, et al. Dosing frequency and medication adherence in chronic disease. J Manag Care Pharm. 2012; 18 (7): 527-539.
74. 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; 8 (5): e63479.
75. Heidbuchel H, Verhamme P, Alings M, et al. EHRA practical guide on the use of new oral anticoagulants in patients with non-valvular atrial fibrillation: executive summary. Eur Heart J. 2013; 34 (27): 2094-2106.
76. Laliberté F, Nelson WW, Lefebvre P, Schein JR, Rondeau-Leclaire J, Duh MS,. Impact of daily dosing frequency on adherence to chronic medications among nonvalvular atrial fibrillation patients. Adv Ther. 2012; 29 (8): 675-690.
77. Beyer-Westendorf J, Werth S, Koehler C, et al. Real life efficacy of rivaroxaban for stroke prevention in atrial fibrillation-first results of the prospective NOAC registry (NCT01588119). Blood (ASH Annual Meeting Abstracts). 2012; 120 (21). Abstract 1156.
78. 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 (4): 530-538.
79. Beyer-Westendorf J, Koehler C, Werth S, et al. Real life efficacy and safety of rivaroxaban for extended VTE treatment-first results of the prospective NOAC registry (NCT01588119). Blood (ASH Annual Meeting Abstracts). 2012; 120 (21). Abstract 2267.
80. Schulman S, Shortt B, Robinson M, Eikelboom JW,. Adherence to anticoagulant treatment with dabigatran in a real-world setting. J Thromb Haemost. 2013; 11 (7): 1295-1299.
81. Larsen TB, Rasmussen LH, Skjøth F, et al. Efficacy and safety of dabigatran etexilate and warfarin in "real-world" patients with atrial fibrillation: a prospective nationwide cohort study. J Am Coll Cardiol. 2013; 61 (22): 2264-2273.
82. Beyer-Westendorf J, Ebertz F, Förster 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 (6): 1247-1257.
83. Laliberté F, Bookhart BK, Nelson WW, et al. Impact of once-daily versus twice-daily dosing frequency on adherence to chronic medications among patients with venous thromboembolism. Patient. 2013; 6 (3): 213-224.
84. Robert-Ebadi H, Righini M,. Anticoagulation in the elderly. Pharmaceuticals. 2010; 3 (12): 3543-3569.
85. Bamber L, Wang MY, Prins MH, et al. Patient-reported treatment satisfaction with oral rivaroxaban versus standard therapy in the treatment of acute symptomatic deep-vein thrombosis. Thromb Haemost. 2013; 110 (4): 732-741.
86. Prins MH, Bamber L, Cano SJ, et al. Patient-reported treatment satisfaction with oral rivaroxaban versus standard therapy in the treatment of pulmonary embolism; results from the EINSTEIN PE trial. Thromb Res. 2015; 135 (2): 281-288.
87. Kreutz R,. A clinical and pharmacologic assessment of once-daily versus twice-daily dosing for rivaroxaban. J Thromb Thrombolysis. 2014; 38 (2): 137-149.
88. ® Prescribing Information. 2015. Published January 2015. Web site. http://dsi.com/prescribing-information-portlet/getPIContent?productName=Savaysa&inline=true. Accessed January 2015.
89. Wong PC, Crain EJ, Xin B, et al. Apixaban, an oral, direct and highly selective Factor Xa inhibitor: in vitro, antithrombotic and antihemostatic studies. J Thromb Haemost. 2008; 6 (5): 820-829.
90. Wienen W, Stassen JM, Priepke H, Ries UJ, Hauel N,. In-vitro profile and ex-vivo anticoagulant activity of the direct thrombin inhibitor dabigatran and its orally active prodrug, dabigatran etexilate. Thromb Haemost. 2007; 98 (1): 155-162.
91. Furugohri T, Isobe K, Honda Y, et al. DU-176b, a potent and orally active Factor Xa inhibitor: in vitro and in vivo pharmacological profiles. J Thromb Haemost. 2008; 6 (9): 1542-1549.
92. Perzborn E, Strassburger J, Wilmen A, et al. In vitro and in vivo studies of the novel antithrombotic agent BAY 59-7939-an oral, direct Factor Xa inhibitor. J Thromb Haemost. 2005; 3 (3): 514-521.
93. Mueck W, Stampfuss J, Kubitza D, Becka M,. Clinical pharmacokinetic and pharmacodynamic profile of rivaroxaban. Clin Pharmacokinet. 2014; 53 (1): 1-16.
94. 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; 64 (21): e1-e76.
95. Vo T, Vazquez S, Rondina MT,. Current state of anticoagulants to treat deep venous thrombosis. Curr Cardiol Rep. 2014; 16 (3): 463.
96. Savelieva I, Camm AJ,. Practical considerations for using novel oral anticoagulants in patients with atrial fibrillation. Clin Cardiol. 2013; 37 (1): 32-47.