comparison of warfarin pradaxa and xarelto

PL Detail-Document #271001 −This PL Detail-Document gives subscribers

additional insight related to the Recommendations published in−

PHARMACIST’S LETTER / PRESCRIBER’S LETTER October 2011

More. . . 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

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

Cost of 30-day

supplya

Approved Indications

(Usual Maintenance Dose)b

Clinical Benefit In…c

Antidote/

pre-op, pre-

procedure

washout (if

indicated)

Therapeutic

Considerations

ANTICOAGULANTS (see information about the investigational drug apixaban at the end of the chart)

Dabigatran

(Pradaxa; Pradax

[Canada]):

direct thrombin

inhibitor5,6

(150 mg BID)

U.S.: $262.44

(AWP)

Canada: $103.68

Continued…

U.S.:5

Thromboembolism (e.g., stroke)

prevention in A fib (150 mg BID)5

Canada:6


prevention in A fib (150 mg BID,

110 mg BID for patients over 80 yrs).

VTE prevention post-hip or knee

replacement (220 mg once daily x 10

days [knee] or 28 to 35 days [hip]. If

started 1-4 hrs post-op, initial dose is

110 mg)

A fib: prevents about five more

strokes per 1000 patients per year

than warfarin. Lower rate of

hemorrhagic stroke, higher rate of

major GI bleed7

Post-hip/knee replacement (off-label

[U.S.]): comparable to enoxaparin for

prevention of VTE & mortality

(combined endpoint); comparable

major bleeding8-10

VTE treatment (off-label):

comparable to warfarin for prevention

of recurrent VTE or VTE death

(combined endpoint); comparable

No specific

antidote

See our PL

Detail-

Document,

Reversing

Dabigatran

and

Rivaroxaban

Requires BID dosing for

A fib.5,6

Dispense/store in original

container. Once opened,

discard after four months

(U.S.) or 30 days

(Canada).5,6

To switch from warfarin,

stop warfarin, then start

dabigatran when INR <2.5,6

See product labeling for

instructions for switching

to warfarin, or to/from

injectable anticoagulants.

Check renal function at

baseline, and yearly in

(PL Detail-Document #271001: of 14)



Drug: Mechanism

Cost of 30-day

supplya




Antidote/

pre-op, pre-

procedure

washout (if

indicated)

Therapeutic

Considerations

Dabigatran,

continued

Continued…

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

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 p-




Drug: Mechanism

Cost of 30-day

supplya




Antidote/

pre-op, pre-

procedure

washout (if

indicated)

Therapeutic

Considerations

Dabigatran,

continued

glycoprotein inhibitors

(e.g., ketoconazole)

contraindicated per

Canadian labeling.6 P-

glycoprotein inducers (e.g.,

rifampin, carbamazepine,

St. John’s wort, tenofovir)

could decrease dabigatran

efficacy.6

Avoid per U.S.

labeling.5

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

Continued…

U.S.:12


replacement (10 mg once daily for 35

days [hip] or 12 days [knee] starting 6-

10 hrs post-op, assuming hemostasis

achieved)


prevention in A fib (20 mg once daily

with evening meal to improve

absorption)

Canada:13


replacement (10 mg once daily for 35

days [hip] or 14 days [knee], starting

6-10 hrs post-op, assuming hemostasis

achieved)

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

Detail-

Document,

Reversing

Dabigatran

and

Rivaroxaban

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 p-

glycoprotein and strong

CYP3A4 inhibitors (e.g.,

ketoconazole, itraconazole,

voriconazole,

posiconazole, ritonavir [all

contraindicated, per

Canadian labelling],

clarithromycin,

conivaptan). P-

glycoprotein inducers (e.g.,

rifampin, carbamazepine,

phenytoin, St. John’s wort)

may decrease efficacy.12.13

Avoid per U.S. labeling.12




Drug: Mechanism

Cost of 30-day

supplya




Antidote/

pre-op, pre-

procedure

washout (if

indicated)

Therapeutic

Considerations

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; co-

administer with

caution.12,13

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)

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




Drug: Mechanism

Cost of 30-day

supplya




Antidote/

pre-op, pre-

procedure

washout (if

indicated)

Therapeutic

Considerations

Warfarin,

continued

Prevention of reinfarction and

thromboembolism (e.g., stroke) post-

MI (adjunct)

TIA (adjunct)

(Note: warfarin dosing variable and

patient specific.)

alone (combined endpoint)26

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]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.

ANTIPLATELETS

Aspirin: inhibits

cyclo-oxygenase

(81 mg once daily)

U.S.: <$1

Canada: <$1

Continued…

U.S. (vascular indications):33

Secondary prevention after ischemic

stroke, TIA, MI, or unstable angina,

(81 to 325 mg daily)

Acute MI (81 to 325 mg daily)

Chronic stable angina (81 to 325 mg

daily)

Revascularization procedures

(81 to 325 mg daily)

Canada (vascular indications):44

Primary CV event prevention (off-

label, 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

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




Drug: Mechanism

Cost of 30-day

supplya




Antidote/

pre-op, pre-

procedure

washout (if

indicated)

Therapeutic

Considerations

Aspirin,

continued

Secondary prevention after MI or

unstable angina (81 to 325 mg once

daily)

Primary prevention of MI in high-

risk 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)

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

Cilostazol (Pletal,

generics [U.S.

only]): inhibits

platelet

phosphodiesterase

III54

(100 mg BID)

U.S.: $24.32

Continued…

U.S.:53

Intermittent claudication (100 mg

BID)

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




Drug: Mechanism

Cost of 30-day

supplya




Antidote/

pre-op, pre-

procedure

washout (if

indicated)

Therapeutic

Considerations

Cilostazol,

continued

safety with aspirin

unknown.53

CYP3A4 and CYP2C19

interactions.53

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)


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 (off-

label, 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

Used with aspirin in

A fib (not first-line), non-

STEMI, 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




Drug: Mechanism

Cost of 30-day

supplya




Antidote/

pre-op, pre-

procedure

washout (if

indicated)

Therapeutic

Considerations

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

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 cyclo-

oxygenase &

platelet adenosine

uptake50,51

(One capsule BID)

U.S.: $215.32

Canada: $53.33

U.S.:50

Secondary prevention of stroke post-

stroke/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




Drug: Mechanism

Cost of 30-day

supplya




Antidote/

pre-op, pre-

procedure

washout (if

indicated)

Therapeutic

Considerations

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

Platelet

transfusion

suggested56

/

Washout:

seven days35

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

Ticagrelor

(Brilinta): blocks

platelet ADP

P2Y12 receptor58

Continued…

U.S.:58


90 mg twice daily, with aspirin 81 mg)

Canada:60


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

/

BID dosing.58,60

Reversible binding to

platelet receptor.58

Adverse effects

of note include

bradycardia, dyspnea, and

gynecomastia in men.58,59




Drug: Mechanism

Cost of 30-day

supplya




Antidote/

pre-op, pre-

procedure

washout (if

indicated)

Therapeutic

Considerations

Ticagrelor,

continued

(90 mg BID)

U.S.: $260.78

Canada: $95.90

Washout:

five days58,60

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. Co-

administer with caution.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 post-

stroke/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

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

Co-

administer only with close

monitoring.63




Drug: Mechanism

Cost of 30-day

supplya




Antidote/

pre-op, pre-

procedure

washout (if

indicated)

Therapeutic

Considerations

INVESTIGATIONAL ORAL ANTICOAGULANT

Apixaban (Eliquis):

direct factor Xa

inhibitor1

Not yet available

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.

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

Letter/Prescriber’s Letter. October 2011.

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