Comparison of Warfarin Pradaxa and Xarelto

PL Detail-Document #271001
This PL Detail-Document gives subscribers additional insight related to the Recommendations published in
PHARMACISTS LETTER / PRESCRIBERS LETTER

October 2011
Comparison of Oral Antithrombotics

(Last modified November 2011) The recent proliferation of oral anticoagulants and antiplatelet agents has health care professionals questioning how to choose among them. The newest anticoagulants are dabigatran (Pradaxa, Pradax [Canada]) and rivaroxaban (Xarelto). Also look for the direct factor Xa inhibitor apixaban possibly in 2012, and edoxaban and betrixaban in the next few years. The following chart compares the indications, clinical benefit, antidotes, washout, and other therapeutic considerations for these agents. Abbreviations: ACS = acute coronary syndrome; ADP = adenosine diphosphate; A fib = atrial fibrillation; AV = arteriovenous; AWP = average wholesale price; BID = twice daily; CAD = coronary artery disease; DVT = deep vein thrombosis; LMWH = low molecular weight heparin; LVD = left ventricular dysfunction; MI = myocardial infarction; PE= pulmonary embolism; STEMI = ST segment elevation myocardial infarction; TIA = transient ischemic attack; VTE = venous thromboembolism Drug: Mechanism Approved Indications Clinical Benefit Inc Antidote/ Therapeutic b (Usual Maintenance Dose) pre-op, preConsiderations Cost of 30-day procedure supplya washout (if indicated) ANTICOAGULANTS (see information about the investigational drug apixaban at the end of the chart) Dabigatran U.S.:5 A fib: prevents about five more No specific Requires BID dosing for (Pradaxa; Pradax strokes per 1000 patients per year antidote Thromboembolism (e.g., stroke) A fib.5,6 5 [Canada]): than warfarin. Lower rate of prevention in A fib (150 mg BID) Dispense/store in original direct thrombin hemorrhagic stroke, higher rate of See our PL container. Once opened, inhibitor5,6 major GI bleed7 DetailCanada:6 discard after four months Document, Thromboembolism (e.g., stroke) (U.S.) or 30 days (150 mg BID) Post-hip/knee replacement (off-label Reversing prevention in A fib (150 mg BID, (Canada).5,6 U.S.: $262.44 [U.S.]): comparable to enoxaparin for Dabigatran 110 mg BID for patients over 80 yrs). To switch from warfarin, (AWP) prevention of VTE & mortality and VTE prevention post-hip or knee stop warfarin, then start (combined endpoint); comparable Rivaroxaban replacement (220 mg once daily x 10 dabigatran when INR <2.5,6 8-10 Canada: $103.68 major bleeding days [knee] or 28 to 35 days [hip]. If See product labeling for started 1-4 hrs post-op, initial dose is instructions for switching VTE treatment (off-label): 110 mg) to warfarin, or to/from comparable to warfarin for prevention injectable anticoagulants. of recurrent VTE or VTE death Check renal function at Continued (combined endpoint); comparable baseline, and yearly in
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Copyright 2011 by Therapeutic Research Center P.O. Box 8190, Stockton, CA 95208 ~ Phone: 209-472-2240 ~ Fax: 209-472-2249 www.pharmacistsletter.com ~ www.prescribersletter.com ~ www.pharmacytechniciansletter.com
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Drug: Mechanism Cost of 30-day supplya Dabigatran, continued
Approved Indications (Usual Maintenance Dose)b
Clinical Benefit Inc
Antidote/ pre-op, preprocedure washout (if indicated)
Therapeutic Considerations
major bleeding11
patients over 75 years or with CrCl < 50 mL/min.5 Renal dosing: A fib (U.S.), use 75 mg BID if CrCl 15 to 30 mL/min.5 VTE, use 75 mg x 1, then 150 mg once daily if CrCl 30 to 50 mL/min.6 Canada, contraindicated if CrCl < 30 mL/min.6 Causes dyspepsia in over 10% of patients.7 Caution if 75 years & over (over 75 years, Canada), poor renal function, or underweight.5,6,43 Co-administration with
aspirin or clopidogrel about doubles bleeding risk.6
Continued
P-glycoprotein inhibitors (e.g., dronedarone, ketoconazole, verapamil, quinidine, amiodarone) can increase dabigatran levels. Dabigatran dose adjustment may be needed (see labeling).5,6 Strong pMore. . .
Drug: Mechanism Cost of 30-day supplya Dabigatran, continued
Rivaroxaban (Xarelto): direct factor Xa inhibitor12,13 (10, 15, or 20 mg once daily) U.S.: $262.44 (AWP) (10 mg once daily) Canada: $287.06
U.S.:12 VTE prevention post-hip or knee replacement (10 mg once daily for 35 days [hip] or 12 days [knee] starting 610 hrs post-op, assuming hemostasis achieved) Thromboembolism (e.g., stroke) prevention in A fib (20 mg once daily with evening meal to improve absorption)
Post-hip/knee replacement: at least as effective as enoxaparin for prevention of VTE or mortality (combined endpoint); comparable major bleeding14-17 A fib (off-label [Canada]): comparable to warfarin for preventing stroke or systemic embolism in patients with relatively high stroke risk. Comparable major bleeding, but INR in therapeutic range only 55% of time. Lower rate of hemorrhagic stroke, higher rate of major GI bleed. Increase in events after stopping may reflect poor transition to warfarin, not hypercoagulability.18 DVT treatment (off-label): comparable to enoxaparin/warfarin for prevention of recurrent VTE;
No specific antidote See our PL DetailDocument, Reversing Dabigatran and Rivaroxaban
Canada:13 VTE prevention post-hip or knee replacement (10 mg once daily for 35 days [hip] or 14 days [knee], starting 6-10 hrs post-op, assuming hemostasis achieved) Continued
glycoprotein inhibitors (e.g., ketoconazole) contraindicated per Canadian labeling.6 Pglycoprotein inducers (e.g., rifampin, carbamazepine, St. Johns wort, tenofovir) could decrease dabigatran efficacy.6 Avoid per U.S. labeling.5 Once daily dosing.12,13.18 For A fib, some data suggest once daily dosing insufficient, but BID dosing untested.66 Avoid use with drugs that are BOTH pglycoprotein and strong CYP3A4 inhibitors (e.g., ketoconazole, itraconazole, voriconazole, posiconazole, ritonavir [all contraindicated, per Canadian labelling], clarithromycin, conivaptan). Pglycoprotein inducers (e.g., rifampin, carbamazepine, phenytoin, St. Johns wort) may decrease efficacy.12.13 Avoid per U.S. labeling.12
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Drug: Mechanism Cost of 30-day supplya Rivaroxaban, continued
comparable bleeding19
Check renal function periodically (U.S.).12 Canada, monitor if CrCl close to 30 mL/min.13 A fib indication requires renal dosing (15 mg with evening meal for CrCl 15 to 50 mL/min).12 For VTE prevention, avoid if CrCl < 30 mL/min.12,13 Avoid use with other anticoagulants; monitor during transition periods.12 Antiplatelets may increase bleeding risk; coadminister with caution.12,13 Vitamin K/ Washout: five days20,21,41 Gold standard oral anticoagulant; over 50 years experience. INR monitoring required at least every four weeks.20,21 Many drug and food interactions. For VTE, long-term, benefit may not outweigh risk in patients with high bleeding risk.24
Warfarin (Coumadin, generics): inhibits formation of vitamin-K dependent clotting factors20,21 (5 mg once daily) U.S.: $6.65 Canada: $3.43 Continued
U.S.:20 Prevention/treatment of venous thrombosis/PE Prevention/treatment of thromboembolism due to A fib or prosthetic heart valve Secondary prevention post-MI Canada:21 Prevention/treatment of venous thrombosis/PE Prevention/treatment of thromboembolism due to A fib
A fib: prevents stroke (NNT = 32 vs placebo for one year to prevent one stroke)22 PE/DVT (with initial use of heparin): reduces risk of recurrence and mortality [Evidence level B; lower quality RCTs]23 Post-MI: reduces reinfarction, stroke, and mortality (INR 2.8 to 4.8);25 warfarin (INR 2 to 2.5) plus aspirin (75 mg once daily) superior to aspirin alone or warfarin (INR 2.8 to 4.2)
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Drug: Mechanism Cost of 30-day supplya Warfarin, continued
Prevention of reinfarction and thromboembolism (e.g., stroke) postMI (adjunct) TIA (adjunct) (Note: warfarin dosing variable and patient specific.)
alone (combined endpoint)26 Rheumatic mitral valve disease (offlabel): reduces embolic events and mortality in patients with embolic history; reduces embolic events in patients with A fib, promotes resolution of left atrial thrombus [Evidence level B; clinical cohort]29-31 Mechanical heart valve (off-label, Canada): reduces embolism and valve thrombosis (mostly based on nonrandomized, uncontrolled case series)32
Not more effective than aspirin for noncardioembolic stroke.28 Use with aspirin increases bleeding risk. But combo may benefit certain high-risk mechanical heart valve patients. Benefit may also outweigh risk in A fib or VTE history plus recent stent, recent CABG, or new stroke despite INR in therapeutic range.39 Potential for significant interactions with inducers/inhibitors of CYP2C9, 2C19, 1A2, and 3A4. Platelet transfusion38/ Washout: five to 10 days35 In A fib patients with no stroke risk factors, aspirin 81 to 325 mg daily recommended instead of anticoagulation.42,65 For primary prevention of cardiovascular disease, reserve aspirin for certain high-risk patients (See PL Detail-Document, Aspirin for Primary Prevention).34
ANTIPLATELETS Aspirin: inhibits U.S. (vascular indications):33 cyclo-oxygenase Secondary prevention after ischemic stroke, TIA, MI, or unstable angina, (81 mg once daily) (81 to 325 mg daily) U.S.: <$1 Acute MI (81 to 325 mg daily) Chronic stable angina (81 to 325 mg Canada: <$1 daily) Revascularization procedures (81 to 325 mg daily) Canada (vascular indications):44 Continued
Primary CV event prevention (offlabel, U.S.): reduces MI in men, ischemic stroke in high-risk women34 Post-ACS: reduces risk of mortality, re-infarction, and stroke27 Acute MI: reduces vascular mortality33 Chronic stable angina (off-label, Canada): reduces risk of MI or
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Drug: Mechanism Cost of 30-day supplya Aspirin, continued
Cilostazol (Pletal, generics [U.S. only]): inhibits platelet phosphodiesterase III54 (100 mg BID) U.S.: $24.32 Continued
Secondary prevention after MI or unstable angina (81 to 325 mg once daily) Primary prevention of MI in highrisk patients (81 to 325 mg once daily) To reduce risk of TIA or recurrent stroke (81 to 325 mg once daily) Acute MI (160 mg immediately, then daily for 30 days. Then as for secondary prevention) Prevention of VTE post-hip replacement (650 mg BID) (note: current guidelines recommend against aspirin monotherapy for VTE prophylaxis)45 Reduction of platelet adhesiveness in hemodialysis patients with silicone rubber AV cannula (dose not specified) Post-carotid endarterectomy (dose not specified) U.S.:53 Intermittent claudication (100 mg BID)
sudden death, or serious vascular events (combined endpoints)47 TIA or minor noncardioembolic stroke: reduces risk of stroke or death, or vascular death, MI, or stroke (combined endpoints)64 Post-coronary stent (off-label): prevents stent thrombosis40 A fib (off-label): Efficacy inferior to warfarin and not much better than no treatment at all in real world use. [Evidence level B; clinical cohort study].67
Post-coronary stent, dual antiplatelet therapy is initially indicated.40 Use with warfarin increases bleeding risk. But combo may benefit certain high-risk mechanical heart valve patients. Benefit may also outweigh risk in A fib or VTE history plus recent stent, recent CABG, or new stroke despite INR in therapeutic range.39
Intermittent claudication: increases walking distance53
No specific antidote/ Washout: two to three days41
Use with aspirin enhances platelet inhibition vs aspirin alone. No increase in bleeding risk vs aspirin alone noted in patients receiving concomitant cilostazol plus aspirin in clinical trials (n=201). But long-term
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Drug: Mechanism Cost of 30-day supplya Cilostazol, continued
Clopidogrel (Plavix): blocks platelet ADP P2Y12 receptor36,37 (75 mg once daily) U.S.: $188.66 Canada: $85.22
U.S.:36 ACS (300 mg load, then 75 mg once daily, plus aspirin 81 to 325 mg daily; can skip loading dose in STEMI) Recent stroke (75 mg once daily) Recent MI (75 mg once daily) Peripheral artery disease (75 mg once daily) Canada:37 Secondary prevention in patient with atherosclerosis (i.e., patients with a history of stroke or MI, or with peripheral artery disease) (75 mg once daily) ACS (300 mg loading dose, then 75 mg once daily, plus aspirin 81 to 325 mg once daily; can skip loading dose in STEMI) Thromboembolism (e.g., stroke) prevention in A fib (75 mg once daily plus aspirin 81 mg once daily)
Non-STEMI (with aspirin): reduces cardiovascular death, MI, stroke, or refractory ischemia (combined endpoint)36,37 STEMI (with aspirin): reduces risk of death or death, re-infarction, and/or stroke (combined endpoint)36,37 Recent MI: reduces risk of stroke, MI, or vascular death (combined endpoint)36,37 Recent noncardioembolic stroke (offlabel, U.S.): reduces risk of stroke, MI, or vascular death (combined endpoint)36,37 Peripheral artery disease: reduces risk of stroke, MI, or vascular death (combined endpoint)28,36,37 A fib (with aspirin): reduces vascular events (e.g., stroke).37,46 But combo not as effective as warfarin, and not safer.68
Platelet transfusion suggested36,37/ Washout: five to seven days35
safety with aspirin unknown.53 CYP3A4 and CYP2C19 interactions.53 Used with aspirin in A fib (not first-line), nonSTEMI, STEMI, symptomatic CAD, and post-stent.27,37,46,68 Clopidogrel may be superior to aspirin for secondary prevention of stroke post-stroke/TIA.52 Efficacy affected by CYP2C19 inhibitors and pharmacogenetics.54
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Drug: Mechanism Cost of 30-day supplya Dipyridamole (Persantine, generics): inhibits platelet adenosine uptake48,49 (75 mg four times daily) U.S.: $88.79 Canada: $56.99
U.S.:48 Prevention of thromboembolism post-heart valve replacement, with warfarin (75 to 100 mg four times daily) Canada:49 Prevention of thromboembolism post-heart valve replacement (100 mg four times daily)
Mechanical heart valve (with warfarin or warfarin plus aspirin): thromboembolic rates 0.6 to 1.5% per year in case series32
Antidote/ pre-op, preprocedure washout (if indicated) No specific antidote/ Washout: two to three days41
Four times daily dosing.48,49 Despite indication, data insufficient to recommend for valvular heart disease.32
Dipyridamole extended release 200 mg/aspirin 25 mg (Aggrenox): inhibits cyclooxygenase & platelet adenosine uptake50,51 (One capsule BID) U.S.: $215.32 Canada: $53.33
U.S.:50 Secondary prevention of stroke poststroke/TIA (one capsule BID) Canada:51 Secondary prevention of stroke in patients who have had a stroke or TIA (one capsule BID)
Secondary prevention of stroke: reduces stroke risk; superior to placebo or monotherapy with aspirin or dipyridamole extended-release50,51
No specific antidote/ Washout: five to 10 days (see aspirin)
BID dosing.50,51 Not substitutable with dipyridamole plus aspirin separately.52 Drug of choice for secondary prevention of stroke post-stroke/TIA.52
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Drug: Mechanism Cost of 30-day supplya Prasugrel (Effient): blocks platelet ADP P2Y12 receptor57 (10 mg once daily) U.S.: $202.68 Canada: $86.18
U.S.:56 ACS managed with PCI (including stenting), with aspirin (60 mg loading dose, then 10 mg once daily with aspirin 81 to 325 mg once daily) Canada:57 ACS managed with PCI (including stenting), with aspirin (60 mg loading dose, then 10 mg once daily with aspirin 81 to 325 mg once daily)
ACS managed with PCI (with aspirin): reduces cardiovascular death, MI, and stroke (combined endpoint) by 2% vs clopidogrel plus aspirin; higher bleeding risk55
Antidote/ pre-op, preprocedure washout (if indicated) Platelet transfusion suggested56/ Washout: seven days35
Ticagrelor (Brilinta): blocks platelet ADP P2Y12 receptor58 Continued
U.S.:58 ACS (180 mg loading dose, then 90 mg twice daily, with aspirin 81 mg) Canada:60 ACS (180 mg loading dose, then 90 mg twice daily, with aspirin 81 mg)
ACS (with aspirin): reduces risk of cardiovascular death, MI, or stroke (combined endpoint) and stent thrombosis vs clopidogrel (with aspirin)59
Aminocaproic acid or tranexamic acid and/or recombinant factor VIIa suggested60/
Consider dose reduction in patients <60 kg.56 Not recommended in patients 75 or older.56,57 Contraindicated in stroke/TIA history.56,57 Efficacy not affected by pharmacokinetics or CYP450 inhibitors.56,57 Consider for patients with low bleeding risk and high cardiovascular event risk, and/or who have had a cardiac event while taking clopidogrel, and for patients with reduced CYP2C19 activity due to a genetic variation or interacting medication. Use with warfarin increases bleeding risk.56,57 Co-administer with caution.57 BID dosing.58,60 Reversible binding to platelet receptor.58 Adverse effects of note include bradycardia, dyspnea, and gynecomastia in men.58,59
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Drug: Mechanism Cost of 30-day supplya Ticagrelor, continued (90 mg BID) U.S.: $260.78 Canada: $95.90
Antidote/ pre-op, preprocedure washout (if indicated) Washout: five days58,60
Ticlopidine (generic only): blocks platelet ADP P2Y12 receptor (250 mg BID) U.S.: $111.68 Canada: $32.57
U.S.:61 Secondary prevention of stroke poststroke/TIA (250 mg BID) Prevention of stent thrombosis (250 mg BID with low-dose aspirin) Canada:63 Prevention of first or recurrent stroke in patients with a history of thromboembolic stroke, minor stroke, reversible ischemic neurological deficit (RIND), TIA, or transient monocular blindness (TMB) (250 mg BID)
Post-TIA/noncardioembolic stroke: reduces risk of stroke, MI, and vascular death (combined endpoint)28 Post-coronary stent (with aspirin): Better than aspirin alone or warfarin for preventing death, revascularization, thrombosis, or MI (combined endpoint)62
Platelet transfusion suggested63/ Washout: ten to 14 days61,63
Maintenance aspirin dose 81 mg. Higher doses of aspirin reduce efficacy of ticagrelor.58 Consider for patients who have had a cardiac event while taking clopidogrel, and for patients with reduced CYP2C19 activity due to a genetic variation or interacting medication. CYP3A4 interactions.58,60 Not studied with oral anticoagulants. Coadminister with caution.60 Not a first-line agent.28,52 BID dosing. Adverse effects of note include neutropenia, thrombotic thrombocytopenic purpura, diarrhea, and rash.28 Long-term safety with anticoagulants not established.61 Coadminister only with close monitoring.63
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Drug: Mechanism Cost of 30-day supplya
Antidote/ pre-op, preprocedure washout (if indicated) No specific antidote
INVESTIGATIONAL ORAL ANTICOAGULANT Apixaban (Eliquis): Not yet approved in U.S. or Canada direct factor Xa inhibitor1 Not yet available
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
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.
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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 A Definition High-quality randomized controlled trial (RCT) High-quality meta-analysis (quantitative systematic review) Nonrandomized clinical trial Nonquantitative systematic review Lower quality RCT Clinical cohort study Case-control study Historical control Epidemiologic study Consensus Expert opinion Anecdotal evidence In vitro or animal study 10.
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Adapted from Siwek J, et al. How to write an evidence-based clinical review article. Am Fam Physician 2002;65:251-8.
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Project Leader in preparation of this PL DetailDocument: Melanie Cupp, Pharm.D., BCPS
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References
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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 th evidence-based clinical practice guidelines (8 edition). Chest 2008;133(Suppl 6):776S-814S. 28. Albers GW, Amarenco P, Easton JD, et al. Antithrombotic and thrombolytic therapy for ischemic stroke: American College of Chest Physicians th evidence-based clinical practice guidelines (8 edition). Chest 2008;133(Suppl 6):630S-69S. 29. Adams GF, Merrett JD, Hutchinson WM, Pollock AM. 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, OGara PT, Madias C, et al. Valvular and structural heart disease: American College of Chest Physicians evidence-based clinical practice th guidelines (8 edition). Chest 2008;133(Suppl 6):593S-629S. 33. Product information for Bayer Aspirin. http://bayeraspirinpro.com/en/home/productinformation/#prod2. (Accessed September 5, 2011). 34. PL Detail-Document, Aspirin for Primary Prevention. Pharmacists Letter/Prescribers Letter. February 2010. 35. PL Detail-Document, Discontinuing Antiplatelet Agents. Pharmacists Letter/Prescribers Letter. September 2011. 36. Product information for Plavix. Bristol Myers Squibb/Sanofi Pharmaceuticals Partnership. Bridgewater, NJ 08807. May 2011. 37. Product monograph for Plavix. Sanofi-Aventis Canada, Inc. Laval, QC H7L 4A8. May 2011. 38. Ho LL. Warfarin, antiplatelet drugs and their interactions. Aust Prescr 2002;25:81-5. 39. Douketis J. Combination warfarin-ASA therapy: which patients should receive it, which patients should not, and why? Thromb Res 2011;127:513-7. 40. PL Detail-Document, Antiplatelet Therapy for Coronary Stents. Pharmacists Letter/Prescribers Letter. June 2010. 41. PL Detail-Document, Managing Warfarin & Antiplatelet Drugs Perioperatively. Pharmacists Letter/Prescribers Letter. August 2008. 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 th guidelines (8 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. Pharmacists Letter/Prescribers 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. Pharmacists Letter/Prescribers 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;357:200115. 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.
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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;367:190312.
Cite this document as follows: PL Detail-Document, Comparison of Oral Antithrombotics. Letter/Prescribers Letter. October 2011.
Pharmacists
Evidence and Recommendations You Can Trust

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Comparison of Warfarin Pradaxa and Xarelto

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PL Detail-Document #271001

PHARMACISTS LETTER / PRESCRIBERS LETTER

Comparison of Oral Antithrombotics

(PL Detail-Document #271001: Page 2 of 14)

Drug: Mechanism Cost of 30-day supplya Dabigatran, continued

Approved Indications (Usual Maintenance Dose)b

Clinical Benefit Inc

Antidote/ pre-op, preprocedure washout (if indicated)

aspirin or clopidogrel about doubles bleeding risk.6

(PL Detail-Document #271001: Page 3 of 14)

Drug: Mechanism Cost of 30-day supplya Dabigatran, continued

Approved Indications (Usual Maintenance Dose)b

Clinical Benefit Inc

Antidote/ pre-op, preprocedure washout (if indicated)

No specific antidote See our PL DetailDocument, Reversing Dabigatran and Rivaroxaban

(PL Detail-Document #271001: Page 4 of 14)

Drug: Mechanism Cost of 30-day supplya Rivaroxaban, continued

Approved Indications (Usual Maintenance Dose)b

Clinical Benefit Inc

Antidote/ pre-op, preprocedure washout (if indicated)

(PL Detail-Document #271001: Page 5 of 14)

Drug: Mechanism Cost of 30-day supplya Warfarin, continued

Approved Indications (Usual Maintenance Dose)b

Clinical Benefit Inc

Antidote/ pre-op, preprocedure washout (if indicated)

(PL Detail-Document #271001: Page 6 of 14)

Drug: Mechanism Cost of 30-day supplya Aspirin, continued

Approved Indications (Usual Maintenance Dose)b

Clinical Benefit Inc

Antidote/ pre-op, preprocedure washout (if indicated)

Intermittent claudication: increases walking distance53

No specific antidote/ Washout: two to three days41

(PL Detail-Document #271001: Page 7 of 14)

Drug: Mechanism Cost of 30-day supplya Cilostazol, continued

Approved Indications (Usual Maintenance Dose)b

Clinical Benefit Inc

Antidote/ pre-op, preprocedure washout (if indicated)

Platelet transfusion suggested36,37/ Washout: five to seven days35

(PL Detail-Document #271001: Page 8 of 14)

Approved Indications (Usual Maintenance Dose)b

Clinical Benefit Inc

No specific antidote/ Washout: five to 10 days (see aspirin)

(PL Detail-Document #271001: Page 9 of 14)

Approved Indications (Usual Maintenance Dose)b

Clinical Benefit Inc

Ticagrelor (Brilinta): blocks platelet ADP P2Y12 receptor58 Continued

Aminocaproic acid or tranexamic acid and/or recombinant factor VIIa suggested60/

(PL Detail-Document #271001: Page 10 of 14)

Approved Indications (Usual Maintenance Dose)b

Clinical Benefit Inc

Antidote/ pre-op, preprocedure washout (if indicated) Washout: five days58,60

Platelet transfusion suggested63/ Washout: ten to 14 days61,63

(PL Detail-Document #271001: Page 11 of 14)

Drug: Mechanism Cost of 30-day supplya

Approved Indications (Usual Maintenance Dose)b

Clinical Benefit Inc

Antidote/ pre-op, preprocedure washout (if indicated) No specific antidote

(PL Detail-Document #271001: Page 12 of 14)

Project Leader in preparation of this PL DetailDocument: Melanie Cupp, Pharm.D., BCPS

(PL Detail-Document #271001: Page 13 of 14)

(PL Detail-Document #271001: Page 14 of 14)

Evidence and Recommendations You Can Trust

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