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PL Detail-Document #320506
−This PL Detail-Document gives subscribers

additional insight related to the Recommendations published in−
PHARMACIST’S LETTER / PRESCRIBER’S LETTER
May 2016
Comparison of Oral Anticoagulants

The recent proliferation of oral anticoagulants has healthcare professionals questioning how to choose among them. The newest anticoagulants are,
apixaban (Eliquis), dabigatran (Pradaxa), edoxaban (Savaysa, U.S.), and rivaroxaban (Xarelto). Also look for the direct factor Xa inhibitor
betrixaban in the next few years. The following chart compares the indications, clinical benefit, antidotes, washout, switching to/from warfarin, and
other therapeutic considerations for these agents.
Abbreviations: A fib = atrial fibrillation; AV = arteriovenous; BID = twice daily; CABG = coronary artery bypass graft; CAD = coronary artery
disease; CrCl = creatinine clearance; DVT = deep vein thrombosis; INR = international normalized ratio; LMWH = low molecular weight heparin;
MI = myocardial infarction; NNT = number needed to treat; PCI = percutaneous coronary intervention; PE = pulmonary embolism; P-gp = p-
glycoprotein; PTCA = percutaneous transluminal coronary angioplasty; TIA = transient ischemic attack; VTE = venous thromboembolism.
Apixaban (Eliquis) (direct factor Xa inhibitor)
Approved Indications and U.S.:1
Usual Dose  Thromboembolism (e.g., stroke) prevention in nonvalvular A fib (5 mg BID; 2.5 mg BID for patients with two or more
of the following: age 80 years and older, weight 60 kg or less, serum creatinine 1.5 mg/dL or greater)
 VTE prevention post-hip or knee replacement (2.5 mg twice daily for 35 days [hip] or 12 days [knee] starting
12 to 24 hrs post-op)
 DVT/PE treatment (10 mg BID for seven days, then 5 mg BID)
 DVT/PE prevention of recurrence (2.5 mg BID after at least six months of treatment)
Canada:2
 Thromboembolism (e.g., stroke) prevention in A fib (in patients with CrCl >25 mL/min., 5 mg BID; 2.5 mg BID for
patients with two or more of the following: age 80 years and older, weight 60 kg or less, serum creatinine
133 umol/L or greater). Data limited if CrCl 15 to 24 mL/min; no dosing recommendation can be made.2
 VTE prevention post-hip or knee replacement (2.5 mg twice daily for 32 to 38 days [hip] or 10 to 14 days [knee],
starting 12 to 24 hrs post-op, assuming hemostasis achieved)
 DVT/PE treatment (10 mg BID for seven days, then 5 mg BID)
 DVT/PE prevention of recurrence (2.5 mg BID after at least six months of treatment)
Renal Dosing  A fib indication, see above. Canada: not recommended if CrCl <15 mL/min or on dialysis.2
 DVT/PE prevention/recurrence indications, Canada: caution if CrCl 15 to 29 mL/min, but no dosage adjustment
recommended. Not recommended if CrCl <15 mL/min or on dialysis.2
Continued…
More. . .
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(PL Detail-Document #320506: Page 2 of 12)
Apixaban, continued
Clinical Benefit In…a A fib: for every 1000 patients treated per year, apixaban prevents three more strokes, avoids ten major bleeds, and
prevents four deaths compared to warfarin.3
Post-hip/knee replacement: at least as effective as enoxaparin for preventing VTE; comparable bleeding.4,5
DVT/PE treatment/prevention of recurrence: comparable to enoxaparin/warfarin for prevention of recurrent VTE or
VTE death (combined endpoint); less bleeding.40
Antidote/pre-op, pre- No specific antidote. See our PL Detail-Documents, Stopping Antithrombotics Before Surgery and Managing
procedure washout Antithrombotics Before Minor Procedures.
(if indicated)
Therapeutic  Requires BID dosing.1,2
Considerations  Not recommended in patients with prosthetic heart valves.1,2 Canada: not recommended in hemodynamically
significant rheumatic heart disease, especially mitral stenosis.2
 Severe liver impairment: not recommended (U.S.).1 Canada: contraindicated in hepatic disease with coagulopathy
and clinically significant bleeding risk.2
 Prophylax for at least 10 to 14 days after hip or knee replacement, and up to 35 days, especially after hip replacement.17
 For VTE treatment, continue for at least three months.18 Benefit of extended use may not outweigh risk in patients
with high bleeding risk.18
Switching To/From Other  To switch from warfarin, stop warfarin, then start apixaban when INR <2.1,2
Anticoagulants  To switch to warfarin: apixaban increases INR, thus confounding initial warfarin dosing.1,2 U.S.: Consider starting a
parenteral anticoagulant plus warfarin when the next dose of apixaban would have been due, then discontinuing the
parenteral agent when the INR reaches the desired range.1 Canada: continue apixaban with warfarin until the INR is
>2. Use the “usual” initial warfarin dose for the first two days. Thereafter, check INR just prior to the next dose of
apixaban to minimize apixaban interference with the INR.2
 See product labeling for instructions for switching to/from other anticoagulants.
Select Drug Interactions  U.S.: reduce dose by 50% with strong inhibitors of BOTH CYP3A4 and P-gp (e.g., itraconazole, ketoconazole,
ritonavir, clarithromycin). Avoid in patients already taking 2.5 mg BID.1 Canada: contraindicated. Canadian
contraindication also includes posaconazole, voriconazole, and HIV protease inhibitors.2
 Avoid strong inducers of BOTH CYP3A4 and P-gp (e.g., carbamazepine, phenytoin, phenobarbital, St. John’s wort,
rifampin).1,2
Continued…  Caution with antiplatelets and anticoagulants (U.S.).1 Canada: anticoagulants contraindicated; caution with
More. . .
Apixaban, continued
Select Drug Interactions, antiplatelets. Prasugrel and ticagrelor not recommended.2
Continued  Dual antiplatelet therapy about doubles bleeding risk.6
Cost of 30-day supplyb 2.5 mg BID or 5 mg BID. U.S.: $359.92, Canada: $103.68
Dabigatran (Pradaxa) (direct thrombin inhibitor)

Usual Dose  Thromboembolism (e.g., stroke) prevention in nonvalvular A fib (150 mg BID)
 DVT/PE treatment (following 5 to 10 days’ treatment with a parenteral anticoagulant)/prevention of recurrence
(150 mg BID). (Start 0 to 2 hours before the next dose of parenteral anticoagulant would have been due, or at the time
of discontinuation of heparin drip.)
 VTE prevention post-hip replacement (220 mg once daily x 28 to 35 days. If started on day of surgery [1 to 4 hrs post-
op, assuming hemostasis achieved], initial dose is 110 mg).
Canada:8
 Thromboembolism (e.g., stroke) prevention in A fib (150 mg BID; 110 mg BID for patients >80 years, and for patients
at higher risk of bleeding, including patients >75 years of age with at least one other bleeding risk factor; also consider
for other elderly.
 VTE prevention post-hip or knee replacement (220 mg once daily x 10 days [knee] or 28 to 35 days [hip]. If started on
day of surgery, normally within 1 to 4 hrs post-op, assuming hemostasis achieved, initial dose is 110 mg. Consider
150 mg once daily for patients over 75 years).
 DVT/PE treatment (following 5 to 10 days’ treatment with a parenteral anticoagulant)/prevention of recurrence
(150 mg BID; 110 mg BID for patients >80 years, and for patients at higher risk of bleeding, including patients
>75 years of age with at least one other bleeding risk factor). (Start 0 to 2 hours before the next dose of parenteral
anticoagulant would have been due, or at the time of discontinuation of heparin drip.)
Renal Dosing  Check renal function at baseline, yearly (Canada), and when clinically indicated.7,8
 Also see drug interactions section, below.
 Canada, contraindicated if CrCl <30 mL/min.8
 A fib (U.S.): use 75 mg BID if CrCl 15 to 30 mL/min.7 No dosing information for CrCl <15 mL/min or dialysis.7
 DVT/PE treatment/prevention and VTE prevention post-hip replacement (U.S.): no dosing information for
CrCl <30 mL/min or dialysis.7
 DVT/PE treatment/prevention (Canada): for CrCl 30 to 50 mL/min., a dose reduction to 110 mg BID can be
considered based on risk/benefit, but is not recommended.8
 VTE prevention post-hip/knee replacement (Canada), use 75 mg x 1 (1 to 4 hrs post-op), then 150 mg once daily if
CrCl 30 to 50 mL/min.8
More. . .
Dabigatran, continued
Clinical Benefit In…a A fib: prevents about five more strokes per 1000 patients per year than warfarin. Lower rate of hemorrhagic and
ischemic stroke, higher rate of major GI bleed, comparable overall bleeding.10
Post-hip/knee replacement: comparable to enoxaparin for prevention of VTE & mortality (combined endpoint);
comparable major bleeding.11-13
DVT/PE treatment/prevention of recurrence: comparable to warfarin for prevention of recurrent VTE or VTE death
(combined endpoint); comparable major bleeding.14
procedure washout (if ind.) Antithrombotics Before Minor Procedures.
Therapeutic  Requires BID dosing for A fib and DVT/PE treatment/prevention indication.7,8
Considerations  Causes gastrointestinal symptoms in over 10% of patients.7
 Caution if 75 years or older, poor renal function, or underweight.7-9
 Contraindicated with mechanical heart valve, and not recommended with bioprosthetic valves (U.S.).7 Canada:
contraindicated in patients requiring anticoagulation for a prosthetic heart valve. Not recommended in patients with
hemodynamically significant rheumatic heart disease, especially mitral stenosis.8
 Dispense/store in original package.7,8 Once bottle opened, use within 4 months.7,c
 For VTE treatment, continue for at least three months.8,18 Benefit of extended use may not outweigh risk in patients
Switching To/From Other  To switch from warfarin, stop warfarin, then start dabigatran when INR <2.7,8
Anticoagulants  To switch to warfarin, start warfarin three days (if CrCl >50 mL/min), two days (if CrCl 30 to 50 mL/min), or one day
(if CrCl 15 to 30 mL/min [U.S.]) before discontinuing dabigatran.7,8 No recommendations are available for patients
with CrCl <15 mL/min.7
More. . .
Dabigatran, continued
Select Drug Interactions  P-gp inhibitors may increase dabigatran levels.7,8
 Ketoconazole, dronedarone, and other strong P-gp inhibitors contraindicated (Canada).8
 A fib indication (U.S.): avoid P-gp inhibitors if CrCl <30 mL/min.7 Reduce dose to 75 mg BID with ketoconazole
or dronedarone if CrCl 30 to 50 mL/min.7
 VTE/PE treatment/prevention (including post-hip replacement)(U.S.):7 avoid use of P-gp inhibitors if
CrCL <50 mL/min.7
 VTE prevention post-hip/knee replacement (Canada): use 150 mg once daily with the P-gp inhibitors amiodarone,
verapamil, and quinidine. Consider 75 mg once daily in patients taking verapamil who also have moderate renal
impairment.8 Verapamil initiation should be avoided following orthopedic surgery in patients already taking
dabigatran.8
 Give dabigatran 2 hrs before quinidine (A fib) or verapamil (Canada).8
 P-gp inducers could decrease dabigatran efficacy.7,8 Avoid P-gp inducers per U.S. labeling (Canada: avoid stronger
inducers [e.g., rifampin, carbamazepine, St. John’s wort]).7,8
 Caution with antiplatelets.7,8 Avoid ticagrelor or prasugrel (Canada).8 Use with aspirin 100 mg or less can be
considered.8 Co-administration with aspirin or clopidogrel about doubles bleeding risk.8 Contraindicated with
anticoagulants (Canada).8
 Drugs that increase gastric pH could reduce efficacy. Take dabigatran at least 2 hrs before antacids. Avoid antacids
for 24 hrs after hip/knee replacement (Canada).8
Cost of 30-day supplyb 150 mg BID. U.S.: $333.57, Canada: $106.80 (Pradaxa savings card can reduce out-of-pocket cost by up to $2400 per
year for U.S. patients with private insurance. Other patients can get a free 30-day supply at www.pradaxa.com.)
Edoxaban (Savaysa) (direct factor Xa inhibitor)

Usual Dose  Thromboembolism (e.g., stroke) prevention in nonvalvular A fib in patients with CrCl <95 mL/min (60 mg once
daily).
 DVT/PE treatment (following 5 to 10 days’ treatment with a parenteral anticoagulant) (60 mg once daily; 30 mg once
daily if body weight <60 kg).
Renal Dosing  A fib: 60 mg once daily for CrCl >50 to <95 mL/min, or 30 mg once daily for CrCl 15 to 50 mL/min. Not for use in
patients with CrCl >95 mL/min.41
 DVT/PE treatment: 30 mg once daily for CrCl 15 to 50 mL/min.
 Not recommended if CrCl <15 mL/min.41
More. . .
Edoxaban (Savaysa), continued

Clinical Benefit In…a A fib: about as effective as warfarin if CrCl <95 mL/min, with lower risk of major bleeding (six fewer bleeds per
1000 patients per year).42
DVT/PE treatment: About as effective as warfarin, with less bleeding (18 fewer bleeds [composite of major plus
clinically relevant nonmajor bleeding] per 1000 patients per year).43
Antidote/pre-op, pre- No specific antidote. Discontinue at least 24 hours before invasive procedures/surgery.41 See our PL Detail-Documents,
procedure washout (if Stopping Antithrombotics Before Surgery and Managing Antithrombotics Before Minor Procedures.
indicated)
Therapeutic  For A fib, does not work as well as warfarin in patients with normal renal function; dose may not be high enough.41
Considerations  Not recommended in patients with mechanical heart valves or moderate to severe mitral stenosis.41
 Not recommended in moderate or severe hepatic impairment.41
Switching To/From Other  To switch from warfarin, stop warfarin, then start edoxaban when INR <2.5.41
Anticoagulants  To switch to warfarin, reduce edoxaban dose by half and start warfarin. Check INR at least weekly and just prior to
edoxaban dose. Stop edoxaban once INR is >2 and is stable.41
Select Drug Interactions  Use with anticoagulants not recommended. Caution with antiplatelets.41
 Avoid rifampin (P-gp inducer).41
 Reduce dose to 30 mg once daily for DVT/PE indication in patients taking azithromycin, clarithromycin, dronedarone,
erythromycin, itraconazole (oral), ketoconazole (oral), quinidine, or verapamil (P-gp inhibitors).41
Cost of 30-day supplyb 60 mg or 30 mg once daily. U.S.: $291.30

Savaysa savings card can reduce out-of-pocket cost to U.S. patients with private insurance to $4 per month
(www.savaysa.com).
Rivaroxaban (Xarelto) (direct factor Xa inhibitor)

Usual Dose  VTE prevention post-hip or knee replacement (10 mg once daily for 35 days [hip] or 12 days [knee] starting
6 to 10 hrs post-op, assuming hemostasis achieved)
 Thromboembolism (e.g., stroke) prevention in nonvalvular A fib (20 mg once daily with evening meal to improve
Continued… absorption)
More. . .
Rivaroxaban (Xarelto) (direct factor Xa inhibitor)

Approved Indications and  DVT/PE treatment/prevention of recurrence (15 mg twice daily x 3 weeks, then 20 mg once daily, with food to
Usual Dose, improve absorption)
continued Canada:16
 VTE prevention post-hip or knee replacement (10 mg once daily for 35 days [hip] or 14 days [knee], starting
6 to 10 hrs post-op, assuming hemostasis achieved)
 Thromboembolism (e.g., stroke) prevention in A fib (20 mg once daily with food to improve absorption)
 DVT/PE treatment/prevention of recurrence (15 mg twice daily x 3 weeks, then 20 mg once daily, with food to
improve absorption). Treatment duration should last a minimum of 3 months.
Renal Dosing  Check renal function at baseline, yearly (Canada), and when clinically indicated.15,16 Canada, monitor if CrCl close to
30 mL/min or potential for worsening renal function.16
 A fib indication requires renal dosing (15 mg with evening meal for CrCl 15 to 50 mL/min [U.S.],
30 to 49 mL/min [Canada]).15,16
 For DVT/PE prevention and treatment and VTE prevention post-hip/knee replacement, avoid if CrCl <30 mL/min.15,16
Clinical Benefit In…a Post-hip/knee replacement: prevents 4 more VTEs compared to LMWH and causes 9 more serious bleeds per
1000 patients treated for 14 days.17
A fib: 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. 21
DVT treatment/prevention of recurrence: comparable to enoxaparin/warfarin for prevention of recurrent VTE;
comparable major bleeding or clinically relevant nonmajor bleeding (combined endpoint).22
PE treatment/prevention of recurrence: comparable to enoxaparin/warfarin for prevention of recurrent VTE; lower rate
of major bleeding23
procedure washout (if Antithrombotics Before Minor Procedures.
indicated)
More. . .
Rivaroxaban (Xarelto), continued

Therapeutic  For A fib, some data suggest once daily dosing insufficient, but BID dosing untested.24
Considerations  Not recommended in patients with prosthetic heart valves,15,16 or (Canada) patients with hemodynamically significant
rheumatic heart disease, especially mitral stenosis.16
 Avoid in patients with moderate or severe liver impairment or liver disease with coagulopathy.15 Canada:
contraindicated in liver disease with bleeding risk.16
 For VTE treatment, continue for at least three months.18 Benefit of extended use may not outweigh risk in patients with
high bleeding risk.18
 Caution in elderly. Underweight patients have slightly increased levels/response.16
Switching To/From Other  To switch from warfarin, stop warfarin, then start rivaroxaban when INR <3 (2.5 or less per Canadian labeling).15,16
Anticoagulants  To switch to warfarin: rivaroxaban increases INR, thus confounding initial warfarin dosing.15,16 U.S.: consider
starting a parenteral anticoagulant plus warfarin when the next dose of rivaroxaban would have been due.15 Canada:
continue rivaroxaban with warfarin until the INR is >2. Use the “usual” initial warfarin dose for the first two days.
Thereafter, check INR just prior to the next dose of rivaroxaban to minimize rivaroxaban interference with the INR.16
 See product labeling for guidance on switching to/from other anticoagulants.
Select drug interactions  Avoid use with drugs that are BOTH P-gp and strong CYP3A4 inhibitors (e.g., ketoconazole, itraconazole,
posaconazole, ritonavir [all contraindicated, per Canadian labeling], conivaptan).15,16 Caution with clarithromycin and
fluconazole (Canadian labeling).16
 In patients with CrCl 15 to <80 mL/min., the decision to use a combined P-gp/moderate CYP3A4 inhibitor (e.g.,
diltiazem, dronedarone, erythromycin, verapamil) is a risk/benefit determination (U.S.).15 Canada: use erythromycin
with caution in patients with mild to moderate renal impairment.16
 Drugs that are P-gp and strong CYP3A4 inducers (e.g., rifampin, carbamazepine, phenytoin, St. John’s wort) may
decrease efficacy.15,16 Avoid.15,16
 Avoid use with other anticoagulants (Canada: contraindicated).15,16 Antiplatelets increase bleeding risk; co-administer
with caution.15,16
Cost of 30-day supplyb 10, 15, or 20 mg once daily

U.S.: $333.27, Canada: $101.62
Xarelto CarePath savings card can reduce out-of-pocket cost to U.S. patients with private insurance to $0 per month
($3400 maximum annual benefit)(www.xareltocarepath.com).
More. . .
Warfarin (Coumadin) (inhibits formation of vitamin-K dependent clotting factors)

Approved Indications U.S.:25
 Prevention/treatment of venous thrombosis/PE
(Note: warfarin dosing  Prevention/treatment of thromboembolism due to A fib or prosthetic heart valve
variable and patient  Secondary prevention post-MI
specific.)
Canada:26
 Prevention/treatment of venous thrombosis/PE
 Prevention/treatment of thromboembolism due to A fib
 Prevention of reinfarction and thromboembolism (e.g., stroke) post-MI (adjunct)
 TIA (adjunct)
Renal Dosing  Adjust per INR testing. Renal function minor determinant of warfarin response.25
 Preferred anticoagulant for A fib with CrCl <15 mL/min.19
Clinical Benefit In…a A fib: prevents stroke (NNT = 32 vs placebo for one year to prevent one stroke).27
Post hip/knee replacement: prevents 3 fewer major clots compared to LMWH and causes two more fatal bleeds per
1000 patients treated for 14 days.17
PE/DVT (with initial use of heparin): reduces risk of recurrence and mortality [Evidence level B; lower quality RCTs]28
Post-MI: reduces reinfarction, stroke, and mortality (INR 2.8 to 4.8);29 warfarin (INR 2 to 2.5) plus aspirin
(75 mg once daily) superior to aspirin alone or warfarin (INR 2.8 to 4.2) alone (combined endpoint).30
Rheumatic mitral valve disease (off-label): 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].31-33
Mechanical heart valve (off-label, Canada): reduces embolism and valve thrombosis.34
Antidote/pre-op, pre- Vitamin K/

procedure washout (if Washout: five days35
indicated) Also see our PL Detail-Documents, Stopping Antithrombotics Before Surgery and Managing Antithrombotics Before
Minor Procedures.
More. . .
Warfarin (Coumadin), continued

Therapeutic  INR monitoring required at least every four weeks.25,26 Goal 2 to 3 for most indications.18
Considerations  Prophylax for at least 10 to 14 days after hip or knee replacement, and up to 35 days, especially after hip replacement.17
 Not more effective than aspirin for noncardioembolic stroke.37
 Preferred anticoagulant for A fib with CAD.39
with high bleeding risk.18,20
Select drug interactions  Many drug and food interactions.
 Potential for significant interactions with inducers/inhibitors of CYP2C9, 2C19, 1A2, and 3A4.
 Use with antiplatelets increases bleeding risk. Benefit of combo (most data with aspirin or clopidogrel) may outweigh
risk in certain high-risk mechanical heart valve patients, or in A fib or VTE history plus recent stent, recent CABG, or
new stroke despite INR in therapeutic range.36,38
Cost of 30-day supplyb 5 mg once daily

U.S.: <$5, Canada: $2.15
a. Based on Level A evidence unless otherwise noted.

b. U.S. cost for dose specified (of generic, if available) is wholesale average cost at time of writing unless otherwise specified. Canadian prices
are wholesale. Does not include cost of monitoring.
c. At the time of publication, Canadian Pradaxa is only available in blister packs.
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.
More. . .
Levels of Evidence venous thromboembolism after knee arthroplasty

In accordance with the trend towards Evidence-Based surgery. J Arthroplasty 2009;24(1):1-9.
12. Eriksson BI, Dahl OE, Rosencher N, et al.
Medicine, we are citing the LEVEL OF EVIDENCE
Dabigatran etexilate versus enoxaparin for
for the statements we publish. prevention of venous thromboembolism after total hip
Level Definition replacement: a randomised, double-blind, non-
A High-quality randomized controlled trial (RCT) inferiority trial. Lancet 2007;370:949-56.
High-quality meta-analysis (quantitative 13. Eriksson BI, Dahl OE, Rosencher N, et al. Oral
systematic review) dabigatran etexilate vs. subcutaneous enoxaparin for
B Nonrandomized clinical trial the prevention of venous thromboembolism after
Nonquantitative systematic review total knee replacement: the RE-MODEL randomized
Lower quality RCT trial. J Thromb Haemost 2007;5:2178-85.
Clinical cohort study 14. Schulman S, Kearon C, Kakkar AK, et al.
Case-control study Dabigatran versus warfarin in the treatment of acute
Historical control venous thromboembolism. N Engl J Med
Epidemiologic study 2009;361:2342-52.
C Consensus 15. Product information for Xarelto. Janssen
Expert opinion Pharmaceuticals, Inc. Titusville, NJ 08560.
D Anecdotal evidence September 2015.
In vitro or animal study 16. Product monograph for Xarelto. Bayer Inc. Toronto,
Adapted from Siwek J, et al. How to write an evidence-based clinical ON M9W 1G6. July 2015.
review article. Am Fam Physician 2002;65:251-8. 17. Falck-Ytter Y, Francis CW, Johanson NA, et al.
Prevention of VTE in orthopedic surgery patients:
antithrombotic therapy and prevention of thrombosis,
Project Leader in preparation of this PL Detail- th
9 ed: American College of Chest Physicians
Document: Melanie Cupp, Pharm.D., BCPS evidence-based clinical practice guidelines. Chest
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thrombin inhibitor dabigatran etexilate vs North submitted up to August 9, 2011.
American enoxaparin regimen for prevention of http://www.fda.gov/downloads/AdvisoryCommittees/
CommitteesMeetingMaterials/Drugs/Cardiovasculara
More. . .
ndRenalDrugsAdvisoryCommittee/UCM270796.pdf. 35. Douketis JD, Spyropoulos AC, Spencer FA, et al.

(Accessed April 11, 2016). Perioperative management of antithrombotic therapy:
25. Product information for Coumadin. Bristol-Myers antithrombotic therapy and prevention of thrombosis,
th
Squibb Company. Princeton, NJ 08543. December 9 ed: American College of Chest Physicians
2015. evidence-based clinical practice guidelines. Chest
26. Product monograph for Coumadin. Bristol-Myers 2012;141(Suppl 2):e326S-50S.
Squibb Canada. Montreal, QC H4S 0A4. October 36. Douketis JD. Combination warfarin-ASA therapy:
2015. which patients should receive it, which patients
27. Singer DE, Albers GW, Dalen JE, et al. should not, and why? Thromb Res 2011;127:513-7.
Antithrombotic therapy in atrial fibrillation: American 37. Lansberg MG, O’Donnell MJ, Khatri P, et al.
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th
practice guidelines (8 edition). Chest stroke: antithrombotic therapy and prevention of
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2008;133(Suppl 6):546S-592S. thrombosis, 9 ed: American College of Chest
28. Barritt DW, Jordan SC. Anticoagulant drugs in the Physicians evidence-based clinical practice
treatment of pulmonary embolism: a controlled trial. guidelines. Chest 2012;141(Suppl 2):e601S-e36S.
Lancet 1960;1:1309-12. 38. PL Detail-Document, Triple Antithrombotic Therapy
29. Smith P, Arnesen H, Holme I. The effect of warfarin Pharmacist’s Letter/Prescriber’s Letter. November
on mortality and reinfarction after myocardial 2013.
infarction. N Engl J Med 1990;323:147-52. 39. You JJ, Singer DE, Howard PA, et al. Antithrombotic
30. Hurlen M, Abdelnoor M, Smith P, et al. Warfarin, therapy for atrial fibrillation: antithrombotic therapy
th
aspirin, or both after myocardial infarction. N Engl J and prevention of thrombosis, 9 ed: American
Med 2002;347:969-74. College of Chest Physicians evidence-based clinical
31. Adams GF, Merrett JD, Hutchinson WM, Pollock AM. practice guidelines. Chest 2012;141(Suppl
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Psychiatry 1974;37:378-83. for the treatment of acute venous thromboembolism.
32. Szekely P. Systemic embolism and anticoagulant N Engl J Med 2013;369:799-808.
prophylaxis in rheumatic heart disease. Br Med J 41. Product information for Savaysa. Daiichi Sankyo,
1964;1:1209-12. Inc. Parsippany, NJ 07054. September 2015.
33. Silaruks S, Thinkhamrop B, Tantikosum W, et al. A 42. Giugliano RP, Ruff CT, Braunwald E, et al.
prognostic model for predicting the disappearance of Edoxaban versus warfarin in patients with atrial
left atrial thrombi among candidates for fibrillation. N Engl J Med 2013;369:2093-104.
percutaneous transvenous mitral commissurotomy. 43. Hokusai-VTE Investigators, Buller HR, Decousus H,
J Am Coll Cardiol 2002;39:886-91. et al. Edoxaban versus warfarin for the treatment of
34. Whitlock RP, Sun JC, Fremes SE, et al. symptomatic venous thromboembolism. N Engl J
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Cite this document as follows: PL Detail-Document, Comparison of Oral Anticoagulants. Pharmacist’s

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PHARMACIST’S LETTER / PRESCRIBER’S LETTER
August 2014
Comparison of Oral Antiplatelets

(Last modified December 2015)
The recent proliferation of oral antiplatelet agents has health care professionals questioning how to choose among them. The following chart
compares the indications, clinical benefit, antidotes, washout, and other therapeutic considerations for these agents.
Abbreviations: ACCP = American College of Chest Physicians; ACS = acute coronary syndrome; ADP = adenosine diphosphate; A fib = atrial fibrillation;
AHA/ACC/HAS = American Heart Association/American College of Cardiology/Heart Rhythm Society; AV = arteriovenous; BID = twice daily; CABG =
coronary artery bypass graft; CAD = coronary artery disease; CCS = Canadian Cardiovascular Society; CrCl = creatinine clearance; CV = cardiovascular;
DVT = deep vein thrombosis; INR = international normalized ratio; LMWH = low molecular weight heparin; MI = myocardial infarction; NNT = number
needed to treat; PCI = percutaneous coronary intervention; PE = pulmonary embolism; PTCA = percutaneous transluminal coronary angioplasty; STEMI =
ST segment elevation myocardial infarction; TIA = transient ischemic attack; VTE = venous thromboembolism.
Aspirin (inhibits cyclo-oxygenase)

Approved Indications U.S. (vascular indications):1
and Usual Maintenance • Acute MI: 160 to 162.5 mg immediately, then once daily for 30 days. Then as for secondary prevention.
Dosec • Secondary prevention of MI: 75 to 325 mg once daily
• Ischemic stroke or TIA: 50 to 325 mg once daily indefinitely
• Chronic stable angina or unstable angina: 75 to 325 mg once daily indefinitely
• Revascularization procedures (CABG: 325 mg once daily starting six hours post-op and continued for one year; PTCA:
325 mg two hours pre-procedure, then 160 to 325 mg once daily indefinitely; carotid endarterectomy: 80 mg daily to
650 mg twice daily started pre-op and continued indefinitely.
• Durlaza (aspirin extended-release): prevention of MI and death (CAD); recurrent stroke or death: 162.5 mg once daily55
Canada (vascular indications):2

• Acute MI: 162 mg chewed/crushed immediately, then once daily for 30 days. Then as for secondary prevention.
• Secondary prevention of MI: 81 to 325 mg once daily
• Primary prevention of non-fatal MI: 81 to 325 mg once daily
• TIA prevention: 81 to 325 mg once daily
• TIA prevention after carotid endarterectomy: dose not specified
• Secondary atherothrombotic stroke prevention: 81 to 325 mg once daily
• Prevention of VTE after total hip replacement: 162 to 325 mg once daily
• Hemodialysis patients with a silicone rubber AV cannula: dose not specified
More. . .
Aspirin, continued
Clinical Benefit In…a Primary CV event prevention (off-label, U.S.): reduces risk of nonfatal MI and stroke in adults ages 50 to 69 years who
are at increased CV risk.3 See our PL Chart, Aspirin for Primary Prevention, for more information.
Post-ACS: reduces risk of CV death, re-infarction, and stroke4
Acute MI: reduces vascular mortality1
Chronic stable angina (off-label, Canada): reduces risk of MI or sudden death, or serious vascular events (combined
endpoints)5
TIA or minor noncardioembolic stroke: reduces risk of stroke or death, or vascular death, MI, or stroke (combined
endpoints)6
Post-coronary stent (off-label): prevents stent thrombosis7
VTE prevention post-hip/knee replacement (off-label, U.S.): prevents 14 fewer VTEs compared to LMWH per 1000
patients treated for 14 days.11 No proof bleeding risk is lower with aspirin.11 LMWH is the preferred option, but aspirin
(162 mg once daily) is better than no prophylaxis in patients eligible for anticoagulation who are not at high bleeding
risk.11,12
A fib (off-label): efficacy inferior to warfarin and not much better than no treatment in “real world” use. [Evidence level
B; clinical cohort study].8 Bleeding risk similar to warfarin in patients over 75 years of age.9
Prevention (after initial anticoagulation) after first episode of unprovoked VTE (off-label): Reduced composite endpoint
of recurrent VTE, MI, and CV death,13 but anticoagulation preferred.10
Antidote/pre-op, pre- Platelet transfusion14/
procedure washout (if Washout: five to ten days15,16
indicated)
Therapeutic • In A fib patients without stroke risk factors (ACCP), or one stroke risk factor (AHA/ACC/HRS), aspirin 81 mg to 325
Considerations mg daily alternative to no therapy or oral anticoagulation, respectively.17,19 CCS: aspirin 81 mg daily is suggested for A
Fib patients with arterial disease but no other stroke risk factors.18
• A drug of choice for secondary prevention of recurrent stroke, after a stroke or TIA.49
• Post-coronary stent, dual antiplatelet therapy is initially indicated.7
• 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.22
More. . .
Aspirin, continued
Select drug interactions • Use with anticoagulants increases bleeding risk.30 Benefit of combo (most data with warfarin) may outweigh risk in
certain high-risk mechanical heart valve patients, or in A fib or VTE history plus recent stent, recent CABG, or new stroke
despite INR in therapeutic range.30

U.S.: <$5, Canada: <$5
Cilostazol (Pletal, generics [U.S.]) (inhibits platelet phosphodiesterase III)

and Usual Maintenance • Intermittent claudication (100 mg BID)
Dosec
Clinical Benefit In…a Intermittent claudication: increases walking distance20
Antidote/pre-op, pre- No specific antidote/

procedure washout (if Washout: two to three days16
indicated)
Therapeutic Use with aspirin enhances platelet inhibition vs aspirin alone. No increase in bleeding risk vs aspirin alone noted in
considerations patients receiving concomitant cilostazol plus aspirin in clinical trials (n=201). But long-term safety with aspirin
unknown.20
Select drug interactions • Requires dose reduction to 50 mg BID with moderate or strong CYP3A4 and CYP2C19 inhibitors.20
• Use caution with anticoagulants.30
Cost of 30-day supplyb 100 mg BID

U.S.: $13.50
Clopidogrel (Plavix, generics) (inhibits platelet ADP P2Y12 receptor)
and Usual Maintenance • ACS (300 mg load, then 75 mg once daily, plus aspirin 75 to 325 mg daily; can skip loading dose in STEMI)
Dosec • Recent stroke (75 mg once daily)
• Recent MI (75 mg once daily)
• Peripheral artery disease (75 mg once daily)
Continued…
More. . .
Clopidogrel, continued
Indications/dose, Canada:24
continued • Secondary prevention in 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 80 to 325 mg once daily; can skip loading dose in
STEMI)
• Thromboembolism (e.g., stroke) prevention in A fib patients with at least one vascular event risk factor, low bleeding
risk, and for whom anticoagulation is unsuitable (75 mg once daily plus aspirin 75 to 100 mg once daily)
Clinical Benefit In…a Non-ST-segment elevation ACS (with aspirin): reduces cardiovascular death, MI, stroke, or refractory ischemia
(combined endpoint)23,24
STEMI (with aspirin): reduces risk of death, or death, re-infarction, or stroke (combined endpoint)23,24
Recent MI: reduces risk of stroke, MI, or vascular death (combined endpoint)23,24
Recent noncardioembolic stroke: reduces risk of stroke, MI, or vascular death (combined endpoint)23,24
Peripheral artery disease: reduces risk of stroke, MI, or vascular death (combined endpoint)23,24
A fib (with aspirin; off-label U.S.): reduces vascular events (e.g., stroke).24 Combo not as effective as warfarin, and not
safer.25
PCI (with aspirin): reduces cardiovascular events vs aspirin alone (NNT = 53 for 12 months).56
Antidote/pre-op, pre- Platelet transfusion suggested23,24/

procedure washout (if Washout: five to seven days15,23,24
indicated)
Therapeutic • Used with aspirin in A fib (not first-line), post-ACS, and post-stent.17,25,27
considerations • Clopidogrel may be superior to aspirin for secondary prevention of stroke post-stroke/TIA.28
• A drug of choice for secondary prevention of stroke post-stroke/TIA.29,49
• Does not affect overall mortality in stent patients, whether used for 12 months or <6 months, with aspirin.53
Select drug interactions • Efficacy affected by CYP2C19 inhibitors and pharmacogenetics.26
• Use with anticoagulants increases bleeding risk.30 Benefit of combo (most data with warfarin) may outweigh risk in
certain high-risk mechanical heart valve patients, or in A fib or VTE history plus recent stent, recent CABG, or new stroke
despite INR in therapeutic range.30
U.S.: <$10, Canada: $21.30
More. . .
Dipyridamole (Persantine, generics) (inhibits platelet adenosine uptake)

and Usual Maintenance • Prevention of thromboembolism post-heart valve replacement, with warfarin (75 to 100 mg four times daily)
Dosec
Canada:32
• Prevention of thromboembolism post-heart valve replacement (100 mg four times daily)
Clinical Benefit In…a Mechanical heart valve (with warfarin or warfarin plus aspirin): thromboembolic rates 0.6 to 1.5% per year in case series33

procedure washout (if Washout: two to three days16
indicated)
Therapeutic • Four times daily dosing.31,32

considerations • Despite indication, data insufficient to recommend for valvular heart disease.33
Select drug interactions • Use caution with anticoagulants.30
Cost of 30-day supplyb 75 mg four times daily

U.S.: $40.60, Canada: $64.33
Dipyridamole extended-release/aspirin (Aggrenox) (inhibits cyclo-oxygenase & platelet adenosine uptake)

and Usual Maintenance • Secondary prevention of stroke post-ischemic stroke or TIA (one capsule BID)
Dosec
Canada:35
• Secondary prevention of stroke post-stroke or TIA (one capsule BID)
Clinical Benefit In…a Secondary prevention of stroke: reduces stroke risk; superior to placebo or monotherapy with aspirin or dipyridamole
extended-release34,35
More. . .
Dipyridamole extended-release/aspirin, continued

procedure washout (if Washout: five to ten days (see aspirin)
indicated)
Therapeutic • BID dosing.34,35

considerations • Not substitutable with dipyridamole plus aspirin separately.34,35
• Must be protected from excessive moisture.34,35
• A drug of choice for secondary prevention of recurrent stroke, after a stroke or TIA.29,49
Select drug interactions • Use caution with anticoagulants.30
Cost of 30-day supplyb One capsule (200 mg dipyridamole/25 mg aspirin) BID

U.S.: $304.41, Canada: $55.03
Prasugrel (Effient) (inhibits platelet ADP P2Y12 receptor)

and Usual Maintenance • ACS managed with PCI (including stenting), with aspirin (60 mg loading dose, then 10 mg once daily with aspirin 75 to
Dosec 325 mg once daily)
Canada:37
• ACS managed with PCI (including stenting), with aspirin (60 mg loading dose, then 10 mg once daily with aspirin 75 to
325 mg once daily)
Clinical Benefit In…a ACS managed with PCI (with aspirin): reduces cardiovascular death, MI, and stroke (combined endpoint) by 2% vs
clopidogrel plus aspirin; higher bleeding risk38
Antidote/pre-op, pre- Platelet transfusion suggested/

procedure washout (if Washout: seven days36,37
indicated)
Therapeutic • Consider dose reduction to 5 mg once daily in patients <60 kg36 (Canada: use not recommended).37
considerations • Not recommended in patients 75 or older.36,37 U.S.: can consider in high-risk patients (diabetes, history of MI).36
• Contraindicated in patients with stroke/TIA history.36,37
Continued…
More. . .
Prasugrel, continued
Therapeutic • In stent patients, prasugrel/aspirin prevents one more CV event for every 46 patients treated for one year vs
considerations, clopidogrel/aspirin.54
continued • Not more effective than clopidogrel in ACS patients managed without revascularization, and causes more bleeding.50
• Keep in original container with desiccant (U.S.),36 or in original blister packaging (Canada).37
Select drug interactions • Efficacy not affected by pharmacogenetics or CYP450 inhibitors.36,37

• Use caution with anticoagulants.30,36,37 Most data with warfarin.

U.S.: $323.40, Canada: $87.92
Ticagrelor (Brilinta) (inhibits platelet ADP P2Y12 receptor)

and Usual Maintenance • ACS, or MI history (180 mg loading dose, then 90 mg twice daily for the first year, then 60 mg twice daily, with aspirin
Dosec 75 to 100 mg once daily)
Canada:40
• ACS (180 mg loading dose, then 90 mg twice daily, with aspirin 75 to 150 mg once daily)
Clinical Benefit In…a ACS (with aspirin): reduces risk of cardiovascular death, MI, or stroke (combined endpoint) and stent thrombosis by
1.9% vs clopidogrel (with aspirin)41
Secondary MI prevention (with aspirin): 60 mg twice daily plus aspirin prevents a second MI in one in 139 patients
treated over three years vs aspirin alone (when started one to three years post-MI). Combo causes major bleeding in one
in 81 patients. One in 27 patients will discontinue ticagrelor due to shortness of breath. Patients in the study had relatively
high cardiovascular risk and relatively low bleeding risk.51
Antidote/pre-op, pre- No specific antidote. Aminocaproic acid or tranexamic acid and/or recombinant factor VIIa suggested40/
procedure washout (if Washout: five days39,40
indicated)
More. . .
Ticagrelor, continued
Therapeutic • BID dosing.39,40
considerations • Reversible binding to platelet receptor.39
• Adverse effects of note include bradycardia, dyspnea, and gynecomastia in men.39,41
• Contraindicated in patients with a history of intracranial hemorrhage.39,40
• In stent patients, ticagrelor/aspirin prevents one more CV event for every 53 patients and one death for every 71 patients
treated for one year vs clopidogrel/aspirin.52
Select drug interactions • Aspirin doses higher than recommended in product labeling reduce efficacy of ticagrelor (see Usual Dose Section).39,40
• CYP3A4 interactions.39,40
• Avoid simvastatin and lovastatin at doses >40 mg.39
• Monitor digoxin levels if ticagrelor is started or stopped.39
• Not studied with oral anticoagulants.39,40 Co-administer with caution.30,40

U.S.: $285.44, Canada: $95.91
Ticlopidine (generic only) (inhibits platelet ADP P2Y12 receptor)

and Usual Maintenance • Secondary prevention of stroke after thrombotic stroke/TIA in patients who are intolerant to aspirin or who have failed
Dosec aspirin (250 mg BID with food)
• Prevention of stent thrombosis with aspirin (250 mg BID with food, with low-dose aspirin)
Canada:43
• Prevention of stroke in patients with a history of thromboembolic stroke, minor stroke, reversible ischemic neurological
deficit (RIND), TIA, or transient monocular blindness (TMB) in whom other antiplatelet therapy is not appropriate
(250 mg BID)
Clinical benefit in…a Post-TIA/noncardioembolic stroke: reduces risk of stroke, MI, and vascular death (combined endpoint)29
Post-coronary stent (with aspirin): Better than aspirin alone or warfarin for preventing death, revascularization,
thrombosis, or MI (combined endpoint)44
More. . .
Ticlopidine, continued
Antidote/pre-op, pre- Platelet transfusion suggested42,43/
procedure washout (if Washout: ten to 14 days42,43
indicated)
Therapeutic • Not first-line.29,42,43

considerations • BID dosing.
• Adverse effects of note include neutropenia, thrombotic thrombocytopenic purpura, diarrhea, and rash.29
Select drug interactions • Inhibits CYP2C19 and CYP2D6.

• Long-term safety with anticoagulants not established.42 Avoid co-administration.43

U.S.: $77.97, Canada: $20.35
Vorapaxar (Zontivity [U.S.]) (inhibits protease-activated receptor-1 [PAR-1])

Approved Indications Prevention of thrombotic cardiovascular events in patients with a history of MI, or with peripheral artery disease (2.5 mg
and Usual Maintenance once daily), with aspirin and/or clopidogrel at their usual doses.45 (Note that dose may be expressed as 2.5 mg or 2.08 mg;
c
Dose each tablet contains 2.5 mg of vorapaxar sulfate, providing 2.08 mg of vorapaxar.)
Clinical benefit in…a MI history or peripheral artery disease: reduces risk of CV death, MI, stroke, or urgent revascularization (combined
endpoint) in addition to standard care.45
Antidote/pre-op, pre- • No known antidote. Washout may not be feasible; platelet inhibition can last at least four weeks after discontinuation.45
procedure washout (if • In clinical trials, investigators were encouraged not to discontinue the study drug pre-op in patients who required
indicated) CABG.45 However, it was stopped no later than two days prior to surgery in most patients.48 Bleeding events were
treated as for other antiplatelet agents.45
Therapeutic • Avoid use with anticoagulants.45

considerations • Not for ACS.
• Long half-life (eight days [range five to 13 days]).45
• Contraindicated in patients with a history of stroke, TIA, or intracranial hemorrhage.45
• Limited experience with antiplatelets other than aspirin or clopidogrel, and none with monotherapy.45
• In the pivotal clinical trial, 89% of patients were Caucasian, 22% were female, and 33% were 65 years of age or older
Continued… (median age 60 years).45
More. . .
Vorapaxar, continued
Therapeutic • Risk/benefit may be unfavorable in patients over 75 years of age or in those weighing less than 60 kg.46,47
considerations, • For every 1000 patients with no stroke or TIA history, weighing 60 kg or more, vorapaxar prevents 19 CV events over
continued three years, but causes 12 moderate or severe bleeds.21
Select drug interactions Avoid use with strong CYP3A inhibitors or inducers.45
Cost of 30-day supplyb 2.5 mg (2.08 mg) once daily

$267.30
a. Based on Level A evidence unless otherwise noted.
b. U.S. cost for dose specified (of generic, if available) is wholesale average cost at time of writing unless otherwise specified. Canadian prices
are wholesale. Does not include cost of monitoring.
c. See product labeling for dosing in special populations (e.g., renal impairment, etc).
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.
More. . .
Levels of Evidence 6. SALT Collaborative Group. Swedish Aspirin Low-

In accordance with the trend towards Evidence-Based Dose Trial (SALT) of 75 mg aspirin as secondary
prophylaxis after cerebrovascular ischaemic events.
Medicine, we are citing the LEVEL OF EVIDENCE
Lancet 1991;338:1345-9.
for the statements we publish. 7. PL Detail-Document, Oral Antiplatelets for Stent
Level Definition Patients. Pharmacist’s Letter/Prescriber’s Letter.
A High-quality randomized controlled trial (RCT) October 2014.
High-quality meta-analysis (quantitative 8. Olesen JB, Lip GY, Lindhardsen J, et al. Risks of
systematic review) thromboembolism and bleeding with
B Nonrandomized clinical trial thromboprophylaxis in patients with atrial fibrillation:
Nonquantitative systematic review a net clinical benefit analysis using a “real world”
Lower quality RCT nationwide cohort study. Thromb Haemost
Clinical cohort study 2011;106:739-49.
Case-control study 9. Mant J, Hobbs FD, Fletcher K, et al. Warfarin versus
Historical control aspirin for stroke prevention in an elderly community
Epidemiologic study population with atrial fibrillation (the Birmingham
C Consensus Atrial Fibrillation Treatment of the Aged Study,
Expert opinion BAFTA): a randomised controlled trial. Lancet
D Anecdotal evidence 2007;370:493-503.
In vitro or animal study 10. Kearon C, Akl EA, Comerota AJ, et al.
Adapted from Siwek J, et al. How to write an evidence-based clinical Antithrombotic therapy for VTE disease:
review article. Am Fam Physician 2002;65:251-8. antithrombotic therapy and prevention of thrombosis,
th
9 ed: American College of Chest Physicians
evidence-based clinical practice guidelines. Chest
Project Leader in preparation of this PL Detail- 2012;141(Suppl 2):e419S-94S.
Document: Melanie Cupp, Pharm.D., BCPS 11. Falck-Ytter Y, Francis CW, Johanson NA, et al.
Prevention of VTE in orthopedic surgery patients:
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Merck. Presented March 24, 2012. ACC 2012. 37. Product monograph for Effient. Eli Lilly Canada Inc.
Chicago, IL. Toronto, ON M1N 2E8. June 2014.
http://my.americanheart.org/idc/groups/ahamah- 38. Wiviott SD, Braunwald E, McCabe CH, et al.
public/@wcm/@sop/@scon/documents/downloadabl Prasugrel versus clopidogrel in patients with acute
e/ucm_438652.pdf. (Access November 30, 2015). coronary syndromes. N Engl J Med 2007;357:2001-
22. Douketis JD. Combination warfarin-ASA therapy: 15.
which patients should receive it, which patients 39. Product information for Brilinta. AstraZeneca LP.
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23. Product information for Plavix. Bristol-Myers 40. Product monograph for Brilinta. AstraZeneca
Squibb/Sanofi Pharmaceuticals Partnership. Canada Inc. Mississauga, ON L4Y 1M4. September
Bridgewater, NJ 08807. July 2015. 2015.
24. Product monograph for Plavix. Sanofi-Aventis 41. Wallentin L, Becker RC, Budaj A, et al. Ticagrelor
Canada, Inc. Laval, QC H7L 4A8. May 2015. versus clopidogrel in patients with acute coronary
25. The ACTIVE investigators. Clopidogrel plus aspirin syndromes. N Engl J Med 2009;361:1045-57.
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Letter/Prescriber’s Letter. June 2013. coronary-artery stenting. N Engl J Med
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Comparison of Oral Anticoagulants

Dabigatran (Pradaxa) (direct thrombin inhibitor)

Edoxaban (Savaysa) (direct factor Xa inhibitor)

Edoxaban (Savaysa), continued

Cost of 30-day supplyb 60 mg or 30 mg once daily. U.S.: $291.30

Rivaroxaban (Xarelto) (direct factor Xa inhibitor)

Rivaroxaban (Xarelto) (direct factor Xa inhibitor)

Rivaroxaban (Xarelto), continued

Cost of 30-day supplyb 10, 15, or 20 mg once daily

Warfarin (Coumadin) (inhibits formation of vitamin-K dependent clotting factors)

Antidote/pre-op, pre- Vitamin K/

Warfarin (Coumadin), continued

Cost of 30-day supplyb 5 mg once daily

a. Based on Level A evidence unless otherwise noted.

Levels of Evidence venous thromboembolism after knee arthroplasty

ndRenalDrugsAdvisoryCommittee/UCM270796.pdf. 35. Douketis JD, Spyropoulos AC, Spencer FA, et al.

Cite this document as follows: PL Detail-Document, Comparison of Oral Anticoagulants. Pharmacist’s

Evidence and Recommendations You Can Trust…

Subscribers to the Letter can get PL Detail-Documents, like this one,

Comparison of Oral Antiplatelets

Aspirin (inhibits cyclo-oxygenase)

Canada (vascular indications):2

Cost of 30-day supplyb 81 mg once daily

Cilostazol (Pletal, generics [U.S.]) (inhibits platelet phosphodiesterase III)

Antidote/pre-op, pre- No specific antidote/

Cost of 30-day supplyb 100 mg BID

Antidote/pre-op, pre- Platelet transfusion suggested23,24/

Dipyridamole (Persantine, generics) (inhibits platelet adenosine uptake)

Antidote/pre-op, pre- No specific antidote/

Therapeutic • Four times daily dosing.31,32

Select drug interactions • Use caution with anticoagulants.30

Cost of 30-day supplyb 75 mg four times daily

Dipyridamole extended-release/aspirin (Aggrenox) (inhibits cyclo-oxygenase & platelet adenosine uptake)

Dipyridamole extended-release/aspirin, continued

Therapeutic • BID dosing.34,35

Select drug interactions • Use caution with anticoagulants.30

Cost of 30-day supplyb One capsule (200 mg dipyridamole/25 mg aspirin) BID

Prasugrel (Effient) (inhibits platelet ADP P2Y12 receptor)

Antidote/pre-op, pre- Platelet transfusion suggested/

Select drug interactions • Efficacy not affected by pharmacogenetics or CYP450 inhibitors.36,37

Cost of 30-day supplyb 10 mg once daily

Ticagrelor (Brilinta) (inhibits platelet ADP P2Y12 receptor)

Cost of 30-day supplyb 90 mg BID

Ticlopidine (generic only) (inhibits platelet ADP P2Y12 receptor)

Therapeutic • Not first-line.29,42,43

Select drug interactions • Inhibits CYP2C19 and CYP2D6.

Cost of 30-day supplyb 250 mg BID

Vorapaxar (Zontivity [U.S.]) (inhibits protease-activated receptor-1 [PAR-1])

Therapeutic • Avoid use with anticoagulants.45

Cost of 30-day supplyb 2.5 mg (2.08 mg) once daily

Levels of Evidence 6. SALT Collaborative Group. Swedish Aspirin Low-

Copyright © 2014 by Therapeutic Research Center

with stroke and transient ischemic attack: a November 6, 2015.

Cite this document as follows: PL Detail-Document, Comparison of Oral Antiplatelets. Pharmacist’s

Evidence and Recommendations You Can Trust…

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Copyright © 2014 by Therapeutic Research Center

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