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Thromb J. 2014 Jun 24;12:14. doi: 10.1186/1477-9560-12-14. eCollection 2014.

Quality of vitamin K antagonist control and outcomes in atrial fibrillation patients: a meta-analysis and meta-regression.

Thrombosis journal

Elizabeth S Mearns, C Michael White, Christine G Kohn, Jessica Hawthorne, Ju-Sung Song, Joy Meng, Jeff R Schein, Monika K Raut, Craig I Coleman

Affiliations

  1. Department of Pharmacy Practice, University of Connecticut School of Pharmacy, 69 N Eagleville Road, Storrs, CT 06269-3092, USA ; Hartford Hospital Division of Cardiology, 80 Seymour Street, Hartford, CT 06102-5037, USA.
  2. Department of Pharmacy Practice, University of Connecticut School of Pharmacy, 69 N Eagleville Road, Storrs, CT 06269-3092, USA.
  3. Janssen Scientific Affairs, LLC, Raritan, NJ, USA.

PMID: 25024644 PMCID: PMC4094926 DOI: 10.1186/1477-9560-12-14

Abstract

BACKGROUND: Atrial fibrillation (AF) patients frequently require anticoagulation with vitamin K antagonists (VKAs) to prevent thromboembolic events, but their use increases the risk of hemorrhage. We evaluated time spent in therapeutic range (TTR), proportion of international normalized ratio (INR) measurements in range (PINRR), adverse events in relation to INR, and predictors of INR control in AF patients using VKAs.

METHODS: We searched MEDLINE, CENTRAL and EMBASE (1990-June 2013) for studies of AF patients receiving adjusted-dose VKAs that reported INR control measures (TTR and PINRR) and/or reported an INR measurement coinciding with thromboembolic or hemorrhagic events. Random-effects meta-analyses and meta-regression were performed.

RESULTS: Ninety-five articles were included. Sixty-eight VKA-treated study groups reported measures of INR control, while 43 studies reported an INR around the time of the adverse event. Patients spent 61% (95% CI, 59-62%), 25% (95% CI, 23-27%) and 14% (95% CI, 13-15%) of their time within, below or above the therapeutic range. PINRR assessments were within, below, and above range 56% (95% CI, 53-59%), 26% (95% CI, 23-29%) and 13% (95% CI, 11-17%) of the time. Patients receiving VKA management in the community spent less TTR than those managed by anticoagulation clinics or in randomized trials. Patients newly receiving VKAs spent less TTR than those with prior VKA use. Patients in Europe/United Kingdom spent more TTR than patients in North America. Fifty-seven percent (95% CI, 50-64%) of thromboembolic events and 42% (95% CI, 35 - 51%) of hemorrhagic events occurred at an INR <2.0 and >3.0, respectively; while 56% (95% CI, 48-64%) of ischemic strokes and 45% of intracranial hemorrhages (95% CI, 29-63%) occurred at INRs <2.0 and >3.0, respectively.

CONCLUSIONS: Patients on VKAs for AF frequently have INRs outside the therapeutic range. While, thromboembolic and hemorrhagic events do occur patients with a therapeutic INR; patients with an INR <2.0 make up many of the cases of thromboembolism, while those >3.0 make up many of the cases of hemorrhage. Managing anticoagulation outside of a clinical trial or anticoagulation clinic is associated with poorer INR control, as is, the initiation of therapy in the VKA-naïve. Patients in Europe/UK have better INR control than those in North America.

Keywords: Anticoagulation; Atrial fibrillation; International normalized ratio; Vitamin K antagonists

References

  1. Chest. 2008 Jun;133(6 Suppl):546S-592S - PubMed
  2. Z Kardiol. 2005 Mar;94(3):182-6 - PubMed
  3. Lancet. 1996 Sep 7;348(9028):633-8 - PubMed
  4. Ann Pharmacother. 2008 Jan;42(1):62-70 - PubMed
  5. Am J Med. 2002 Jul;113(1):42-51 - PubMed
  6. J Manag Care Pharm. 2009 Apr;15(3):244-52 - PubMed
  7. Stroke. 2001 Dec 1;32(12):2828-32 - PubMed
  8. Lancet. 2007 Aug 11;370(9586):493-503 - PubMed
  9. Stroke. 2011 Sep;42(9):2503-8 - PubMed
  10. Thromb Haemost. 2010 Sep;104(3):633-41 - PubMed
  11. N Engl J Med. 1995 Jul 6;333(1):5-10 - PubMed
  12. N Engl J Med. 2003 Sep 11;349(11):1019-26 - PubMed
  13. Am J Cardiol. 2012 Aug 1;110(3):373-7 - PubMed
  14. Am J Cardiol. 2012 Dec 15;110(12):1799-802 - PubMed
  15. Arch Intern Med. 2000 Apr 10;160(7):967-73 - PubMed
  16. Stroke. 2000 Apr;31(4):817-21 - PubMed
  17. Am J Health Syst Pharm. 2009 May 15;66(10):916-25 - PubMed
  18. Thromb Res. 2007;121(3):347-52 - PubMed
  19. Circ J. 2011;75(8):1852-9 - PubMed
  20. Int J Cardiol. 2005 Jan;98(1):49-55 - PubMed
  21. Curr Med Res Opin. 2014 Jul;30(7):1317-25 - PubMed
  22. Arch Intern Med. 1997 May 12;157(9):978-84 - PubMed
  23. Ann Intern Med. 2004 Nov 16;141(10):745-52 - PubMed
  24. Curr Med Res Opin. 2005 Dec;21(12):1905-13 - PubMed
  25. Am J Geriatr Pharmacother. 2008 Mar;6(1):1-11 - PubMed
  26. Am J Manag Care. 2011 Sep;17(9):617-24 - PubMed
  27. J Am Coll Cardiol. 2007 Jul 24;50(4):309-15 - PubMed
  28. J Thromb Thrombolysis. 2007 Aug;24(1):65-72 - PubMed
  29. Am Heart J. 2005 Apr;149(4):650-6 - PubMed
  30. South Med J. 2000 Jan;93(1):58-61 - PubMed
  31. Int J Clin Pract. 2006 Mar;60(3):258-64 - PubMed
  32. J Am Coll Cardiol. 2004 Oct 19;44(8):1557-66 - PubMed
  33. Stroke. 2000 Sep;31(9):2106-11 - PubMed
  34. Intern Med. 2001 Dec;40(12):1183-8 - PubMed
  35. CMAJ. 2007 May 22;176(11):1589-94 - PubMed
  36. Circulation. 2007 May 29;115(21):2689-96 - PubMed
  37. Circulation. 2006 Aug 15;114(7):e257-354 - PubMed
  38. Chest. 2005 May;127(5):1515-22 - PubMed
  39. Thromb Haemost. 2011 Nov;106(5):968-77 - PubMed
  40. Blood. 2007 Mar 15;109(6):2419-23 - PubMed
  41. J Am Coll Cardiol. 1991 Aug;18(2):349-55 - PubMed
  42. Stroke. 2009 Jan;40(1):235-40 - PubMed
  43. Arch Intern Med. 1987 Sep;147(9):1561-4 - PubMed
  44. Pharmacotherapy. 2008 Jan;28(1):20-6 - PubMed
  45. Am J Cardiol. 1998 Aug 15;82(4):433-7 - PubMed
  46. JAMA. 2003 Nov 26;290(20):2685-92 - PubMed
  47. Int J Cardiol. 2009 Feb 6;132(1):109-13 - PubMed
  48. Lancet. 2003 Nov 22;362(9397):1691-8 - PubMed
  49. Thromb Haemost. 2011 Mar;105(3):535-44 - PubMed
  50. Arch Intern Med. 1998 Aug 10-24;158(15):1641-7 - PubMed
  51. Lancet. 2006 Jun 10;367(9526):1903-12 - PubMed
  52. Thromb Haemost. 2010 Feb;103(2):442-9 - PubMed
  53. BMJ. 2000 May 6;320(7244):1236-9 - PubMed
  54. Am J Manag Care. 2011 Mar;17(3):232-7 - PubMed
  55. Thromb Haemost. 2009 May;101(5):938-42 - PubMed
  56. Circ Cardiovasc Qual Outcomes. 2009 Jul;2(4):297-304 - PubMed
  57. Lancet. 2009 Aug 15;374(9689):534-42 - PubMed
  58. J Manag Care Pharm. 2004 Mar-Apr;10(2):159-65 - PubMed
  59. Stroke. 1997 May;28(5):1015-21 - PubMed
  60. Cerebrovasc Dis. 2005;20(2):114-9 - PubMed
  61. Circulation. 2012 Nov 6;126(19):2309-16 - PubMed
  62. Pharmacotherapy. 2011 Dec;31(12):1161-74 - PubMed
  63. Eur J Intern Med. 2012 Dec;23(8):742-4 - PubMed
  64. Thromb Haemost. 2001 Mar;85(3):418-22 - PubMed
  65. Heart. 2005 Apr;91(4):472-7 - PubMed
  66. J Clin Neurosci. 2005 Nov;12(8):891-4 - PubMed
  67. Am J Cardiol. 2010 Feb 1;105(3):411-6 - PubMed
  68. Blood Coagul Fibrinolysis. 2009 Jan;20(1):47-51 - PubMed
  69. Arch Intern Med. 1994 Jul 11;154(13):1449-57 - PubMed
  70. Eur Heart J. 2011 Sep;32(18):2282-9 - PubMed
  71. Arch Intern Med. 1999 Jun 28;159(12):1322-8 - PubMed
  72. Ann Pharmacother. 2005 Mar;39(3):446-51 - PubMed
  73. Arch Intern Med. 1998 Jul 27;158(14):1513-21 - PubMed
  74. Circ Cardiovasc Qual Outcomes. 2008 Nov;1(2):84-91 - PubMed
  75. Clin J Am Soc Nephrol. 2011 Nov;6(11):2599-604 - PubMed
  76. Arch Intern Med. 2001 Nov 12;161(20):2458-63 - PubMed
  77. Jpn Circ J. 2001 May;65(5):404-8 - PubMed
  78. Chest. 2006 May;129(5):1155-66 - PubMed
  79. Thromb Res. 2000 May 15;98(4):287-93 - PubMed
  80. J Thromb Haemost. 2010 Jan;8(1):101-6 - PubMed
  81. Circulation. 2009 Sep 22;120(12):1029-35, 2 p following 1035 - PubMed
  82. Arch Intern Med. 2001 Sep 24;161(17):2125-8 - PubMed
  83. J Thromb Thrombolysis. 2007 Apr;23(2):83-91 - PubMed
  84. Thromb Res. 2011 Oct;128(4):325-30 - PubMed
  85. Heart. 2004 Nov;90(11):1259-62 - PubMed
  86. J Am Geriatr Soc. 1999 Mar;47(3):366-8 - PubMed
  87. J Intern Med. 2006 Mar;259(3):296-304 - PubMed
  88. Clin Ther. 2004 Sep;26(9):1470-8 - PubMed
  89. JAMA. 2005 Feb 9;293(6):690-8 - PubMed
  90. Bosn J Basic Med Sci. 2009 Nov;9(4):313-9 - PubMed
  91. Yonsei Med J. 2009 Feb 28;50(1):83-8 - PubMed
  92. Am J Geriatr Pharmacother. 2009 Jun;7(3):159-66 - PubMed
  93. J Hum Hypertens. 2011 May;25(5):304-10 - PubMed
  94. Circ J. 2011;75(9):2087-94 - PubMed
  95. N Engl J Med. 2011 Sep 8;365(10):883-91 - PubMed
  96. Am J Hematol. 2012 Apr;87(4):384-7 - PubMed
  97. Chest. 2008 Jun;133(6 Suppl):160S-198S - PubMed
  98. Am Heart J. 2013 Sep;166(3):549-58 - PubMed
  99. Eur J Gen Pract. 2006;12(4):163-8 - PubMed
  100. Eur J Haematol. 2012 Jul;89(1):81-6 - PubMed
  101. N Engl J Med. 2002 Dec 5;347(23):1825-33 - PubMed
  102. Am J Cardiol. 2007 Nov 1;100(9):1419-26 - PubMed
  103. Circ J. 2012;76(9):2104-11 - PubMed
  104. BMJ. 1999 Oct 9;319(7215):958-64 - PubMed
  105. J Am Coll Cardiol. 2010 May 18;55(20):2225-31 - PubMed
  106. J Thromb Haemost. 2008 Jun;6(6):935-43 - PubMed
  107. J Am Coll Cardiol. 2009 Sep 8;54(11):999-1002 - PubMed
  108. Br J Gen Pract. 2006 Sep;56(530):697-702 - PubMed

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