This document is posted to help you gain knowledge. Please leave a comment to let me know what you think about it! Share it to your friends and learn new things together.
Not yet approved in U.S. or Canada A fib: at least as effective as warfarin
for stroke prevention, systemic
embolism, death; less major bleeding1
Post-hip/knee replacement: at least as
effective as enoxaparin for preventing
VTE; comparable bleeding2,3
No specific
antidote Requires BID dosing for
A fib.1
For every 1000 A fib
patients treated for 1.8
years, apixaban prevents
six more strokes, 15 major
bleeds, and eight deaths
compared to warfarin.1
Increases risk of
major bleeding when
added to antiplatelet agent
in patients with acute
coronary syndrome.4
a. U.S. cost for dose specified (of generic, if available) from drugstore.com at time of writing unless otherwise specified. Canadian prescription
drug prices from British Columbia wholesaler Kohl and Frisch Limited. Does not include cost of monitoring.
b. See product labeling for dosing in special populations (e.g., renal impairment, elderly, etc).
c. Based on Level A evidence unless otherwise noted.
Users of this PL Detail-Document are cautioned to use their own professional judgment and consult any other necessary or appropriate sources prior to making
clinical judgments based on the content of this document. Our editors have researched the information with input from experts, government agencies, and national
organizations. Information and internet links in this article were current as of the date of publication.
Levels of Evidence In accordance with the trend towards Evidence-Based
Medicine, we are citing the LEVEL OF EVIDENCE
for the statements we publish.
Level Definition
A High-quality randomized controlled trial (RCT)
High-quality meta-analysis (quantitative
systematic review)
B Nonrandomized clinical trial
Nonquantitative systematic review
Lower quality RCT
Clinical cohort study
Case-control study
Historical control
Epidemiologic study
C Consensus
Expert opinion
D Anecdotal evidence
In vitro or animal study Adapted from Siwek J, et al. How to write an evidence-based clinical
review article. Am Fam Physician 2002;65:251-8.
Project Leader in preparation of this PL Detail-
Document: Melanie Cupp, Pharm.D., BCPS
References 1. Granger CB, Alexander JH, McMurray JJ, et al.
Apixaban versus warfarin in patients with atrial fibrillation. N Engl J Med 2011;Aug 27 [Epub ahead
of print]. 2. Lassen MR, Gallus A, Raskob GE, et al. Apixaban
versus enoxaparin for thromboprophylaxis after hip replacement. N Engl J Med 2011;363:2487-98.
3. Lassen MR, Raskob GE, Gallus A, et al. Apixaban versus enoxaparin for thromboprophylaxis after knee replacement (ADVANCE-2): a randomised double-blind trial. Lancet 2010;375:807-15.
4. Alexander JH, Lopes RD, James S, et al. Apixaban with antiplatelet therapy after acute coronary syndrome. N Engl J Med 2011;365:699-708.
5. Product information for Pradaxa. Boehringer Ingelheim Pharmaceuticals, Inc. Ridgefield, CT 06877. November 2011.
6. Product monograph for Pradax. Boehringer Ingelheim Canada Ltd. Burlington, ON L7L 5H4. June 2011.
7. Connolly SJ, Ezekowitz MD, Yusuf S, et al. Dabigatran versus warfarin in patients with atrial fibrillation. N Engl J Med 2009;361:1139-51.
8. The RE-MOBILIZE Writing Committee. Oral thrombin inhibitor dabigatran etexilate vs North American enoxaparin regimen for prevention of venous thromboembolism after knee arthroplasty surgery. J Arthroplasty 2009;24:1-9.
9. Eriksson BI, Dahl OE, Rosencher N, et al. Dabigatran etexilate versus enoxaparin for prevention of venous thromboembolism after total hip
replacement: a randomised, double-blind, non-inferiority trial. Lancet 2007;370:949-56.
10. Eriksson BI, Dahl OE, Rosencher N, et al. Oral dabigatran etexilate vs. subcutaneous enoxaparin for the prevention of venous thromboembolism after total knee replacement: the RE-MODEL randomized trial. J Thromb Haemost 2007;5:2178-85.
11. Schulman S, Kearon C, Kakkar AK, et al. Dabigatran versus warfarin in the treatment of acute venous thromboembolism. N Engl J Med 2009;361:2342-52.
12. Product information for Xarelto. Janssen Pharmaceuticals, Inc. Titusville, NJ 08560. November 2011.
13. Product monograph for Xarelto. Bayer Inc. Toronto, ON M9W 1G6. September 2011.
14. Eriksson BI, Borris LC, Friedman RJ, et al. Rivaroxaban versus enoxaparin for thromboprophylaxis after hip arthroplasty. N Engl J Med 2008;358:2765-75.
15. Lassen MR, Ageno W, Borris LC, et al. Rivaroxaban versus enoxaparin for thromboprophylaxis after total knee arthroplasty. N Engl J Med 2008;2776-86.
16. Turpie AG, Lassen MR, Davidson BL, et al. Rivaroxaban versus enoxaparin for thromboprophylaxis after total knee arthroplasty (RECORD4): a randomised trial. Lancet 2009;373:1673-80.
17. Kakkar AK, Brenner B, Dahl OE, et al. Extended duration rivaroxaban versus short-term enoxaparin for the prevention of venous thromboembolism after total hip arthroplasty: a double-blind, randomised controlled trial. Lancet 2008;375:31-9.
18. Patel MR, Mahaffey KW, Garg J, et al. Rivaroxaban versus warfarin in nonvalvular atrial fibrillation. N Engl J Med 2011;Aug 10 [Epub ahead of print].
19. EINSTEIN Investigators, Bauersachs R, Berkowitz SD, et al. Oral rivaroxaban for symptomatic venous thromboembolism. N Engl J Med 2010;363:2499-510.
20. Product information for Coumadin. Bristol-Myers Squibb Company. Princeton, NJ 08543. January 2010.
21. Product monograph for Coumadin. Bristol-Myers Squibb Canada. Montreal, QC H4S 0A4. March 2011.
22. Singer DE, Albers GW, Dalen JE, et al. Antithrombotic therapy in atrial fibrillation: American College of Chest Physicians evidence-based clinical practice guidelines (8
th edition). Chest
2008;133(Suppl 6):546S-592S. 23. Barritt DW, Jordan SC. Anticoagulant drugs in the
treatment of pulmonary embolism: a controlled trial. Lancet 1960;1:1309-12.
24. Linkins LA, Choi PT, Douketis JD. Clinical impact of bleeding in patients taking oral anticoagulant therapy for venous thromboembolism: a meta-analysis. Ann Intern Med 2003;139:893-900.
25. Smith P, Arnesen H, Holme I. The effect of warfarin on mortality and reinfarction after myocardial infarction. N Engl J Med 1990;323:147-52.
26. Hurlen M, Abdelnoor M, Smith P, et al. Warfarin, aspirin, or both after myocardial infarction. N Engl J Med 2002;347:969-74
27. Becker RC, Meade TW, Berger PB, et al. The primary and secondary prevention of coronary artery disease: American College of Chest Physicians evidence-based clinical practice guidelines (8
Cerebral embolism and mitral stenosis: survival with and without anticoagulants. J Neurol Neurosurg Psychiatry 1974;37:378-83.
30. Szekely P. Systemic embolism and anticoagulant prophylaxis in rheumatic heart disease. Br Med J
1964;1:1209-12. 31. Silaruks S, Thinkamrop B, Tantikosum W, et al. A
prognostic model for predicting the disappearance of left atrial thrombi among candidates for percutaneous transvenous mitral commissurotomy. J Am Coll Cardiol 2002;39:886-91.
32. Salem DN, O’Gara PT, Madias C, et al. Valvular and structural heart disease: American College of Chest Physicians evidence-based clinical practice guidelines (8
th edition). Chest 2008;133(Suppl
6):593S-629S. 33. Product information for Bayer Aspirin.
http://bayeraspirinpro.com/en/home/product-information/#prod2. (Accessed September 5, 2011).
34. PL Detail-Document, Aspirin for Primary Prevention. Pharmacist’s Letter/Prescriber’s Letter. February 2010.
42. Fuster V, Ryden LE, Cannom DS, et al. ACC/AHA/ESC 2006 guidelines for the management of patients with atrial fibrillation. J Am Coll Cardiol 2006;48:854-906.
43. Legrand M, Mateo J, Aribaud A, et al. The use of dabigatran in elderly patients. Arch Intern Med 2011;171:1285-6.
44. e-CPS [Internet]. Ottawa (ON): Canadian Pharmacists Association; c2011. Aspirin (ASA) monograph [no date]. http://www.e-therapeutics.ca. (Accessed August 31, 2011).
45. Geerts WH, Bergqvist D, Pineo GF, et al. Prevention of venous thromboembolism: American College of Chest Physicians evidence-based clinical practice guidelines (8
th edition). Chest 2008;133(Suppl
6):381S-453S. 46. ACTIVE Investigators, Connolly SJ, Pogue J, et al.
Effect of clopidogrel added to aspirin in patients with atrial fibrillation. N Engl J Med 2009;360:2066-78.
47. Tran H, Anand SS. Oral antiplatelet therapy in cerebrovascular disease, coronary artery disease, and peripheral arterial disease. JAMA 2004;292:1867-74.
48. Product information for Persantine. Boehringer Ingelheim Pharmaceuticals, Inc. Ridgefield, CT 06877. June 2006.
49. Product monograph for Persantine. Boehringer Ingelheim Canada Ltd. Burlington, ON L7L 5H4. May 2005.
50. Product information for Aggrenox. Boehringer
Ingelheim Pharmaceuticals, Inc. Ridgefield, CT 06877. January 2011.
51. Product monograph for Aggrenox. Boehringer Ingelheim Canada Ltd. Burlington, ON L7L 5H4. September 2008.
52. PL Detail-Document, Antiplatelet Agents for Stroke Prevention. Pharmacist’s Letter/Prescriber’s Letter. October 2008.
53. Product information for Pletal. Otsuka Pharmaceutical, Inc. Rockville, MD 20850. November 2007.
54. PL Detail-Document, Proton Pump Inhibitor and Plavix Interaction: An Update. Pharmacist’s Letter/Prescriber’s Letter. July 2009 (last update December 2010).
55. Wiviott SD, Braunwald E, McCabe CH, et al. Prasugrel versus clopidogrel in patients with acute coronary syndromes. N Engl J Med 2007;357:2001-15.
56. Product information for Effient. Eli Lilly and Company. Indianapolis, IN 46285. December 2010.
57. Product monograph for Effient. Eli Lilly Canada Inc. Toronto, ON M1N 2E8. March 2011.
58. Product information for Brilinta. Wilmington, DE 19850. AstraZeneca LP. July 2011.
59. Wallentin L, Becker RC, Budaj A, et al. Ticagrelor versus clopidogrel in patients with acute coronary syndromes. N Engl J Med 2009;361:1045-57.
60. Product monograph for Brilinta. AstraZeneca
Canada Inc. Mississauga, ON L4Y 1M4. May 2011. 61. Product information for ticlopidine. Teva
Pharmaceuticals USA Inc. Sellersville, PA 18960. July 2009.
62. Leon MB, Baim DS, Popma JJ, et al. A clinical trial comparing three antithrombotic-drug regimens after coronary-artery stenting. N Engl J Med 1998;339:1665-71.
63. Product monograph for Teva-ticlopidine. Teva Canada Limited. Toronto, ON M1B 2K9. June 2011.
(PL Detail-Document #271001: Page 14 of 14)
64. SALT Collaborative Group. Swedish Aspirin Low-Dose Trial (SALT) of 75 mg aspirin as secondary prophylaxis after cerebrovascular ischaemic events. Lancet 1991;338:1345-9.
65. Cairns JA, Connolly S, McMurtry S, et al. Canadian Cardiovascular Society atrial fibrillation guidelines 2010: prevention of stroke and systemic thromboembolism in atrial fibrillation and flutter. Can J Cardiol 2011;27:74-90.
66. FDA draft briefing document for the Cardiovascular and Renal Drugs Advisory Committee. NDA 202439. Xarelto tablets. Meeting date September 8, 2011. Document based on applicant’s information submitted up to August 9, 2011. http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/Cardiovasculara
ndRenalDrugsAdvisoryCommittee/UCM270796.pdf. (Accessed November 3, 2011).
67. Olesen JB, Lip GY, Lindhardsen J, et al. Risks of thromboembolism and bleeding with thromboprophylaxis in patients with atrial fibrillation: a net clinical benefit analysis using a “real world” nationwide cohort study. Thromb Haemost
2011;106:739-49. 68. The ACTIVE investigators. Clopidogrel plus aspirin
versus oral anticoagulation for atrial fibrillation in the Atrial fibrillation Clopidogrel Trial with Irbesartan for prevention of Vascular Events (ACTIVE W): a randomized controlled trial. Lancet 2006;367:1903-12.
Cite this document as follows: PL Detail-Document, Comparison of Oral Antithrombotics. Pharmacist’s
Letter/Prescriber’s Letter. October 2011.
Evidence and Recommendations You Can Trust…
3120 West March Lane, P.O. Box 8190, Stockton, CA 95208 ~ TEL (209) 472-2240 ~ FAX (209) 472-2249 Copyright 2011 by Therapeutic Research Center
Subscribers to the Letter can get PL Detail-Documents, like this one, on any topic covered in any issue by going to www.pharmacistsletter.com, www.prescribersletter.com, or