Table of Contents
Thrombosis
Volume 2013, Article ID 640723, 18 pages
http://dx.doi.org/10.1155/2013/640723
Review Article

Dabigatran, Rivaroxaban, or Apixaban versus Warfarin in Patients with Nonvalvular Atrial Fibrillation: A Systematic Review and Meta-Analysis of Subgroups

1Division of Pharmacology and Clinical Evaluation, Medicines for Human Use, Spanish Agency for Medicines and Medical Devices (AEMPS), c/Campezo 1, Edificio 8, 28022 Madrid, Spain
2Department of Clinical Pharmacology, Hospital Clínico San Carlos, c/Prof. Martín Lagos s/n, 28040 Madrid, Spain
3Department of Pharmacology, Universidad Complutense, Plaza Ramón y Cajal s/n, Ciudad Universitaria, 28040 Madrid, Spain
4Department of Clinical Pharmacology, Hospital Clínic, University of Barcelona, c/Villarroel 170, 08036 Barcelona, Spain

Received 26 June 2013; Accepted 11 September 2013

Academic Editor: Omer Iqbal

Copyright © 2013 Antonio Gómez-Outes et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Linked References

  1. A. J. Camm, P. Kirchhof, G. Y. Lip 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),” European Heart Journal, vol. 31, no. 19, pp. 2369–2429, 2010. View at Google Scholar
  2. J. J. You, D. E. Singer, P. A. Howard et al., “Antithrombotic therapy for atrial fibrillation: antithrombotic therapy and prevention of thrombosis, 9th ed: american college of chest physicians evidence-based clinical practice guidelines,” Chest, vol. 141, no. 2, pp. e531S–e575S, 2012. View at Publisher · View at Google Scholar · View at Scopus
  3. P. A. Wolf, R. D. Abbott, and W. B. Kannel, “Atrial fibrillation as an independent risk factor for stroke: the Framingham Study,” Stroke, vol. 22, no. 8, pp. 983–988, 1991. View at Google Scholar · View at Scopus
  4. A. Gómez-Outes, M. L. Suárez-Gea, G. Calvo-Rojas et al., “Discovery of anticoagulant drugs: a historical perspective,” Current Drug Discovery Technologies, vol. 9, no. 2, pp. 83–104, 2012. View at Google Scholar
  5. R. G. Hart, L. A. Pearce, and M. I. Aguilar, “Meta-analysis: antithrombotic therapy to prevent stroke in patients who have nonvalvular atrial fibrillation,” Annals of Internal Medicine, vol. 146, no. 12, pp. 857–867, 2007. View at Google Scholar · View at Scopus
  6. J. Ansell, J. Hirsh, E. Hylek, A. Jacobson, M. Crowther, and G. Palareti, “Pharmacology and management of the vitamin K antagonists: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition),” Chest, vol. 133, no. 6, pp. 160S–198S, 2008. View at Publisher · View at Google Scholar · View at Scopus
  7. L. Friberg, N. Hammar, M. Ringh, H. Pettersson, and M. Rosenqvist, “Stroke prophylaxis in atrial fibrillation: who gets it and who does not? Report from the Stockholm Cohort-study on Atrial Fibrillation (SCAF-study),” European Heart Journal, vol. 27, no. 16, pp. 1954–1964, 2006. View at Publisher · View at Google Scholar · View at Scopus
  8. European Medicines Agency, “Pradaxa-summary of product characteristics,” 2013, http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/000829/WC500041059.pdf.
  9. European Medicines Agency, “Xarelto-summary of product characteristics,” 2013, http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/000944/WC500057108.pdf.
  10. European Medicines Agency, “Eliquis-summary of product characteristics,” 2013, http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/002148/WC500107728.pdf.
  11. G. Calvo-Rojas and A. Gémez-Outes, “Clinical drug development in thromboembolic diseases: regulatory and methodological approach,” Current Drug Discovery Technologies, vol. 9, no. 2, pp. 105–118, 2012. View at Google Scholar · View at Scopus
  12. A. R. Jadad, R. A. Moore, D. Carroll et al., “Assessing the quality of reports of randomized clinical trials: is blinding necessary?” Controlled Clinical Trials, vol. 17, no. 1, pp. 1–12, 1996. View at Publisher · View at Google Scholar · View at Scopus
  13. J. P. Higgins, D. G. Altman, P. C. Gøtzsche et al., “The Cochrane Collaboration's tool for assessing risk of bias in randomised trials,” British Medical Journal, vol. 343, Article ID d5928, 2011. View at Google Scholar
  14. D. E. Singer, Y. Chang, M. C. Fang et al., “The net clinical benefit of warfarin anticoagulation in atrial fibrillation,” Annals of Internal Medicine, vol. 151, no. 5, pp. 297–305, 2009. View at Google Scholar · View at Scopus
  15. A. Liberati, D. G. Altman, J. Tetzlaff et al., “The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate healthcare interventions: explanation and elaboration,” British Medical Journal, vol. 339, Article ID b2700, 2009. View at Publisher · View at Google Scholar · View at Scopus
  16. W. G. Cochran, “The combination of estimates from different experiments,” Biometrics, vol. 10, no. 1, pp. 101–129, 1954. View at Google Scholar
  17. J. P. T. Higgins, S. G. Thompson, J. J. Deeks, and D. G. Altman, “Measuring inconsistency in meta-analyses,” British Medical Journal, vol. 327, no. 7414, pp. 557–560, 2003. View at Google Scholar · View at Scopus
  18. R. DerSimonian and N. Laird, “Meta-analysis in clinical trials,” Controlled Clinical Trials, vol. 7, no. 3, pp. 177–188, 1986. View at Google Scholar · View at Scopus
  19. D. G. Altman, “Confidence intervals for the number needed to treat,” British Medical Journal, vol. 317, no. 7168, pp. 1309–1312, 1998. View at Google Scholar · View at Scopus
  20. N. Mantel and W. Haenszel, “Statistical aspects of the analysis of data from retrospective studies of disease,” Journal of the National Cancer Institute, vol. 22, no. 4, pp. 719–748, 1959. View at Google Scholar
  21. The Nordic Cochrane Centre, The Cochrane Collaboration, Review Manager (RevMan) [Computer program]. Version 5. 1, Copenhagen, 2011.
  22. S. J. Connolly, M. D. Ezekowitz, S. Yusuf et al., “Dabigatran versus warfarin in patients with atrial fibrillation,” The New England Journal of Medicine, vol. 361, no. 12, pp. 1139–1151, 2009. View at Google Scholar
  23. M. R. Patel, K. W. Mahaffey, J. Garg et al., “Rivaroxaban versus warfarin in nonvalvular atrial fibrillation,” The New England Journal of Medicine, vol. 365, no. 10, pp. 883–891, 2011. View at Publisher · View at Google Scholar · View at Scopus
  24. C. B. Granger, J. H. Alexander, J. J. V. McMurray et al., “Apixaban versus warfarin in patients with atrial fibrillation,” The New England Journal of Medicine, vol. 365, no. 11, pp. 981–992, 2011. View at Publisher · View at Google Scholar · View at Scopus
  25. M. D. Ezekowitz, S. Connolly, A. Parekh et al., “Rationale and design of RE-LY: randomized evaluation of long-term anticoagulant therapy, warfarin, compared with dabigatran,” American Heart Journal, vol. 157, no. 5, pp. 805.e2–810.e2, 2009. View at Publisher · View at Google Scholar · View at Scopus
  26. ROCKET AF Study Investigators, “Rivaroxaban-once daily, oral, direct factor Xa inhibition compared with vitamin K antagonism for prevention of stroke and Embolism Trial in Atrial Fibrillation: rationale and design of the ROCKET AF Study,” American Heart Journal, vol. 159, no. 3, pp. 340–347, 2010. View at Google Scholar
  27. R. D. Lopes, J. H. Alexander, S. M. Al-Khatib et al., “Apixaban for Reduction in Stroke and other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) trial: design and rationale,” American Heart Journal, vol. 159, no. 3, pp. 331–339, 2010. View at Publisher · View at Google Scholar · View at Scopus
  28. L. Wallentin, S. Yusuf, M. D. Ezekowitz 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,” The Lancet, vol. 376, no. 9745, pp. 975–983, 2010. View at Publisher · View at Google Scholar · View at Scopus
  29. H.-C. Diener, S. J. Connolly, M. D. Ezekowitz et al., “Dabigatran compared with warfarin in patients with atrial fibrillation and previous transient ischaemic attack or stroke: a subgroup analysis of the RE-LY trial,” The Lancet Neurology, vol. 9, no. 12, pp. 1157–1163, 2010. View at Publisher · View at Google Scholar · View at Scopus
  30. M. D. Ezekowitz, L. Wallentin, S. J. Connolly et al., “Dabigatran and warfarin in vitamin K antagonist-naive and -experienced cohorts with atrial fibrillation,” Circulation, vol. 122, no. 22, pp. 2246–2253, 2010. View at Publisher · View at Google Scholar · View at Scopus
  31. J. W. Eikelboom, L. Wallentin, S. J. Connolly 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, vol. 123, no. 21, pp. 2363–2372, 2011. View at Publisher · View at Google Scholar · View at Scopus
  32. J. Oldgren, M. Alings, H. Darius et al., “Risks for stroke, bleeding, and death in patients with atrial fibrillation receiving dabigatran or warfarin in relation to the CHADS2 score: a subgroup analysis of the Re-Ly trial,” Annals of Internal Medicine, vol. 155, no. 10, pp. 660–667, 2011. View at Google Scholar · View at Scopus
  33. G. Flaker, M. Ezekowitz, S. Yusuf et al., “Efficacy and safety of dabigatran compared to warfarin in patients with paroxysmal, persistent, and permanent atrial fibrillation: results from the RE-LY (Randomized Evaluation of Long-Term Anticoagulation Therapy) study,” Journal of the American College of Cardiology, vol. 59, no. 9, pp. 854–855, 2012. View at Publisher · View at Google Scholar · View at Scopus
  34. S. H. Hohnloser, J. Oldgren, S. Yang et al., “Myocardial ischemic events in patients with atrial fibrillation treated with dabigatran or warfarin in the RE-LY (Randomized evaluation of long-term anticoagulation therapy) trial,” Circulation, vol. 125, no. 5, pp. 669–676, 2012. View at Publisher · View at Google Scholar · View at Scopus
  35. K. A. A. Fox, J. P. Piccini, D. Wojdyla et al., “Prevention of stroke and systemic embolism with rivaroxaban compared with warfarin in patients with non-valvular atrial fibrillation and moderate renal impairment,” European Heart Journal, vol. 32, no. 19, pp. 2387–2394, 2011. View at Publisher · View at Google Scholar · View at Scopus
  36. G. J. Hankey, M. R. Patel, S. R. Stevens et al., “Rivaroxaban compared with warfarin in patients with atrial fibrillation and previous stroke or transient ischaemic attack: a subgroup analysis of ROCKET AF,” The Lancet Neurology, vol. 11, no. 4, pp. 315–322, 2012. View at Publisher · View at Google Scholar · View at Scopus
  37. J. D. Easton, R. D. Lopes, M. C. Bahit et al., “Apixaban compared with warfarin in patients with atrial fibrillation and previous stroke or transient ischaemic attack: a subgroup analysis of the ARISTOTLE trial,” The Lancet Neurology, vol. 11, no. 6, pp. 503–5511, 2012. View at Publisher · View at Google Scholar · View at Scopus
  38. R. D. Lopes, S. M. Al-Khatib, L. Wallentin et al., “Efficacy and safety of apixaban compared with warfarin according to patient risk of stroke and of bleeding in atrial fibrillation: a secondary analysis of a randomised controlled trial,” The Lancet, vol. 380, no. 9855, pp. 1749–1758, 2012. View at Google Scholar
  39. S. J. Connolly, M. D. Ezekowitz, S. Yusuf, P. A. Reilly, and L. Wallentin, “Newly identified events in the RE-LY trial,” The New England Journal of Medicine, vol. 363, no. 19, pp. 1875–1876, 2010. View at Publisher · View at Google Scholar · View at Scopus
  40. R. Nagarakanti, M. D. Ezekowitz, J. Oldgren et al., “Dabigatran versus warfarin in patients with atrial fibrillation: an analysis of patients undergoing cardioversion,” Circulation, vol. 123, no. 2, pp. 131–136, 2011. View at Publisher · View at Google Scholar · View at Scopus
  41. M. Hori, S. J. Connolly, M. D. Ezekowitz, P. A. Reilly, S. Yusuf, and L. Wallentin, “Efficacy and safety of dabigatran vs. warfarin in patients with atrial fibrillation: sub-analysis in Japanese population in RE-LY trial,” Circulation Journal, vol. 75, no. 4, pp. 800–805, 2011. View at Publisher · View at Google Scholar · View at Scopus
  42. H.-C. Diener, J. Eikelboom, S. J. Connolly et al., “Apixaban versus aspirin in patients with atrial fibrillation and previous stroke or transient ischaemic attack: a predefined subgroup analysis from AVERROES, a randomised trial,” The Lancet Neurology, vol. 11, no. 3, pp. 225–231, 2012. View at Publisher · View at Google Scholar · View at Scopus
  43. K.-H. Liesenfeld, T. Lehr, C. Dansirikul et al., “Population pharmacokinetic analysis of the oral thrombin inhibitor dabigatran etexilate in patients with non-valvular atrial fibrillation from the RE-LY trial,” Journal of Thrombosis and Haemostasis, vol. 9, no. 11, pp. 2168–2175, 2011. View at Publisher · View at Google Scholar · View at Scopus
  44. W. Mueck, A. W. A. Lensing, G. Agnelli, H. Decousus, P. Prandoni, and F. Misselwitz, “Rivaroxaban: population pharmacokinetic analyses in patients treated for acute deep-vein thrombosis and exposure simulations in patients with atrial fibrillation treated for stroke prevention,” Clinical Pharmacokinetics, vol. 50, no. 10, pp. 675–686, 2011. View at Google Scholar · View at Scopus
  45. M. D. Ezekowitz, P. A. Reilly, G. Nehmiz et al., “Dabigatran with or without concomitant aspirin compared with warfarin alone in patients with nonvalvular atrial fibrillation (petro study),” American Journal of Cardiology, vol. 100, no. 9, pp. 1419–1426, 2007. View at Publisher · View at Google Scholar · View at Scopus
  46. S. Ogawa, Y. Shinohara, and K. Kanmuri, “Safety and efficacy of the oral direct factor Xa inhibitor apixaban in Japanese patients with non-valvular atrial fibrillation,” Circulation Journal, vol. 75, no. 8, pp. 1852–1859, 2011. View at Publisher · View at Google Scholar · View at Scopus
  47. S. J. Connolly, J. Eikelboom, C. Joyner et al., “Apixaban in patients with atrial fibrillation,” The New England Journal of Medicine, vol. 364, no. 9, pp. 806–817, 2011. View at Publisher · View at Google Scholar · View at Scopus
  48. J. W. Eikelboom, M. O'Donnell, S. Yusuf et al., “Rationale and design of AVERROES: apixaban versus acetylsalicylic acid to prevent stroke in atrial fibrillation patients who have failed or are unsuitable for vitamin K antagonist treatment,” American Heart Journal, vol. 159, no. 3, pp. 348.e1–353.e1, 2010. View at Publisher · View at Google Scholar · View at Scopus
  49. FDA Briefing Information, Dabigatran Etexilate Mesylate Capsules, for the September 20, 2010 Meeting of the Cardiovascular and Renal Drugs Advisory Committee, 2013, http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/CardiovascularandRenalDrugsAdvisoryCommittee/UCM247244.pdf.
  50. “FDA Briefing Information for the September 8, 2011 Meeting of the Cardiovascular and Renal Drugs Advisory Committee,” 2013, http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/CardiovascularandRenalDrugsAdvisoryCommittee/UCM270796.pdf.
  51. FDA. Apixaban Clinical Review Addendum. December 17, 2012, http://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/202155Orig1s000MedR.pdf.
  52. Boehringer Ingelheim Briefing Information, “Dabigatran Etexilate Mesylate Capsules, for the September 20, 2010 Meeting of the Cardiovascular and Renal Drugs Advisory Committee,” 2013, http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/CardiovascularandRenalDrugsAdvisoryCommittee/UCM226009.pdf.
  53. “Johnson & Johnson Briefing Information for the September 8, 2011 Meeting of the Cardiovascular and Renal Drugs Advisory Committee,” http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/CardiovascularandRenalDrugsAdvisoryCommittee/UCM270797.pdf.
  54. M. R. Patel, A. S. Hellkamp, Y. Lokhnygina et al., “Outcomes of discontinuing rivaroxaban compared with warfarin in patients with nonvalvular atrial fibrillation: analysis from the ROCKET AF trial (Rivaroxaban Once-Daily, Oral, Direct Factor Xa Inhibition Compared With Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation),” Journal of the American College of Cardiology, vol. 61, no. 6, pp. 651–658, 2013. View at Google Scholar
  55. L. Wallentin, R. D. Lopes, M. Hanna et al., “ARISTOTLE: efficacy and safety of apixaban compared with Warfarin at different levels of INR control for stroke prevention in 18, 202 patients with atrial fibrillation in the ARISTOTLE trial,” Presentation at the European Society of Cardiology (ESC) Congress 2011. Paris, August 27–31, 2011, http://www.escardio.org/congresses/esc-2011/congress-reports/Pages/709-3-ARISTOTLE.aspx.
  56. F. Dentali, N. Riva, M. Crowther et al., “Efficacy and safety of the novel oral anticoagulants in atrial fibrillation: a systematic review and meta-analysis of the literature,” Circulation, vol. 126, no. 20, pp. 2381–2391, 2012. View at Google Scholar
  57. C. S. Miller, S. M. Grandi, A. Shimony, K. B. Filion, and M. J. Eisenberg, “Meta-analysis of efficacy and safety of new oral anticoagulants (Dabigatran, Rivaroxaban, Apixaban) versus warfarin in patients with atrial fibrillation,” American Journal of Cardiology, vol. 110, no. 3, pp. 453–460, 2012. View at Publisher · View at Google Scholar · View at Scopus
  58. J. W. Eikelboom, S. J. Connolly, R. G. Hart et al., “Balancing the benefits and risks of two doses of dabigatran compared with warfarin in atrial fibrillation,” Journal of the American College of Cardiology, vol. 62, no. 10, pp. 900–908, 2013. View at Publisher · View at Google Scholar
  59. J. F. Meschia, P. Merrill, E. Z. Soliman et al., “Racial disparities in awareness and treatment of atrial fibrillation: the REasons for geographic and racial differences in stroke (REGARDS) study,” Stroke, vol. 41, no. 4, pp. 581–587, 2010. View at Publisher · View at Google Scholar · View at Scopus
  60. J. S. Healey, G. Y. Lip, J. Oldgren et al., “Global variations in the 1-year rates of death and stroke in 15, 340 patients presenting to the emergency department with atrial fibrillation in 47 countries: the RE-LY AF Registry, " Presentation at the European Society of Cardiology (ESC) Congress 2012, Munich, August 25–29,” 2012, http://www.escardio.org/congresses/esc-2012/congress-reports/Pages/711-3-RELY-AF.aspx.
  61. S. J. Connolly, J. Pogue, J. Eikelboom et al., “Benefit of oral anticoagulant over antiplatelet therapy in atrial fibrillation depends on the quality of international normalized ratio control achieved by centers and countries as measured by time in therapeutic range,” Circulation, vol. 118, no. 20, pp. 2029–2037, 2008. View at Publisher · View at Google Scholar · View at Scopus
  62. C. Van Walraven, A. Jennings, N. Oake, D. Fergusson, and A. J. Forster, “Effect of study setting on anticoagulation control: a systematic review and metaregression,” Chest, vol. 129, no. 5, pp. 1155–1166, 2006. View at Publisher · View at Google Scholar · View at Scopus
  63. D. E. Singer, A. S. Hellkamp, J. P. Piccini et al., “Impact of global geographic region on time in therapeutic range on warfarin anticoagulant therapy: data from the rocket AF clinical trial,” Journal of the American Heart Association, vol. 2, no. 1, Article ID e000067, 2013. View at Google Scholar
  64. M. L. Flaherty, “Anticoagulant-associated intracerebral hemorrhage,” Seminars in Neurology, vol. 30, no. 5, pp. 565–572, 2010. View at Publisher · View at Google Scholar · View at Scopus
  65. J. Fletcher, “Subgroup analyses: how to avoid being misled,” British Medical Journal, vol. 335, no. 7610, pp. 96–97, 2007. View at Publisher · View at Google Scholar · View at Scopus
  66. X. Sun, M. Briel, S. D. Walter, and G. H. Guyatt, “Is a subgroup effect believable? Updating criteria to evaluate the credibility of subgroup analyses,” British Medical Journal, vol. 340, Article ID c117, 2010. View at Google Scholar · View at Scopus
  67. S. L. Charland, D. C. Malone, B. C. Agatep et al., “Real-world risk of thromboembolism or bleeding with warfarin or dabigatran therapy in patients with atrial fibrillation, Presentation at the American Heart Association (AHA) Scientific Sessions 2012, Los Angeles, Calif, USA, November 3–7, 2012: abstract 16370,” http://www.abstractsonline.com/plan/ViewAbstract.aspx?mID=2974&sKey=a0bb3efd-f070-4c37-81c3-0ee0ede4c5a4&cKey=b91dba5f-391f-4f6c-a86d-bc17b62b3299&mKey={14145D5B-F96B-4354-8237-8F0937744BA4}.
  68. T. Gomes, M. M. Mamdani, A. M. Holbrook et al., “Rates of hemorrhage during warfarin therapy for atrial fibrillation,” Canadian Medical Association Journal, vol. 185, no. 2, pp. E121–E127, 2013. View at Google Scholar
  69. T. A. Simon, H. Y. Huang, H. Kawabata et al., “How well do the 56, 183 atrial fibrillation patients enrolled in the contemporary novel oral anticoagulant (NOAC) trials reflect the real world?” American Public Health Association (APHA) 140th Annual Meeting & Expo, San Francisco, CA, October 23–31, 2012: paper 270987, https://apha.confex.com/apha/140am/webprogram/Paper270987.html.
  70. Committee for Medicinal Products for Human Use (CHMP), Pradaxa (dabigatran etexilate) European Public Assessment Report (EPAR). Procedure No.: EMEA/H/C/000829/II/0031, 23 August, 2012, http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Assessment_Report_-_Variation/human/000829/WC500131783.pdf.
  71. S. Y. Han, S. T. Palmeri, S. H. Broderick et al., “Quality of anticoagulation with warfarin in patients with nonvalvular atrial fibrillation in the community setting,” Journal of Electrocardiology, vol. 46, no. 1, pp. 45–50, 2013. View at Google Scholar
  72. H. G. Van Spall, L. Wallentin, S. Yusuf et al., “Variation in warfarin dose adjustment practice is responsible for differences in the quality of anticoagulation control between centers and countries: an analysis of patients receiving warfarin in the RE-LY trial,” Circulation, vol. 126, no. 19, pp. 2309–2316, 2012. View at Google Scholar
  73. C. Heneghan, A. Ward, and R. Perera, “Self-monitoring of oral anticoagulation: systematic review and meta-analysis of individual patient data,” The Lancet, vol. 379, no. 9813, pp. 322–334, 2012. View at Publisher · View at Google Scholar · View at Scopus