Objectives. Epidemiology. Pathophysiology 4/1/2013

(1)

The

New

CHEST

Guidelines,

The

Bleeding

War

Continues

Ginger

Warren,

PharmD.,

MCSR

[email protected]

PGY1

Pharmacy

Resident

Valley

Health

System/Bernard

J

Dunn

School

of

Pharmacy,

Shenandoah

University

April

3

rd

_,

₂₀₁₃

I have no relevant financial relationships or interests to declare



Identify

updates/changes

in

the

atrial

fibrillation

(AF)

chapter

of

the

9 th

_edition

_CHEST

_guideline



Choose

an

appropriate

treatment

course

for

a

patient

based

on

a

CHADS

2 score



Recognize

strong

recommendations

as

compared

to

those

with

weak

evidence



Select

appropriate

counseling

points

for

a

patient

starting

on

one

of

the

new

agents

used

in

atrial

fibrillation

Objectives



Atrial

fibrillation

(AF)

is

the

most

common

sustained

cardiac

arrhythmia

1 

Affects

almost

3 million

people

in

the

United

States

1 

Prevalence

increases

with

age

1 

Approximately 9% of patients ≥ 80 years old



In

2005,

estimated

cost

of

treatment

per

year

including

hospitalizations

was

$6.65

billion

2 

Risk

of

ischemic

stroke

w/o

thromboprophylaxis is

5%

per

year

Epidemiology

1. Fuster V, Ryden LE, Cannom DS, Crijns HJ, Curtis AB, Ellenbogen KA, et al. ACC/AHA/ESC 2006 Guidelines for the Management of Patients with Atrial Fibrillation: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the European Society of Cardiology Committee for Practice Guidelines.Circulation. 2006;114(7):e257–354, 2. Coyne KS, Paramore C, Grandy S, Mercader M, Reynolds M, Zimetbaum P. Assessing the direct costs of treating nonvalvular atrial fibrillation in the United States.Value Health. 2006 Sep–Oct;9(5):348–56



Shortened

action

potential

&

refractory

period



rapid

atrial

rate

Pathophysiology

(2)

Risk

Factor

(CHADS

2

)

Point Value

C

ongestive

heart

failure/LV

dysfunction

1 H

ypertension

1 A

ge

≥

75 years

old

(yo)

1 D

iabetes

mellitus

1 Prior

history

of

S

toke

or

transient ischemic

attack

2 Stroke

Risk

Stratification

Risk Factor

(CHADS

2

‐

VASc)

Point

Value

Congestive

heart

failure/LV

dysfunction

1 Hypertension

1 Age

≥

75 yo

2 Diabetes

mellitus

1 Prior

history

of

Stoke

or

transient ischemic

attack

2 Vascular Disease

1 Age 65

– 74

yo

1 Female Sex

1 Ischemic

Stroke

and

Systemic

Embolism

Risk

Factor

Relative

Risk

Congestive

heart

failure

1.4 History

of

hypertension

1.6 Advanced

age

(continuous,

per

decade)

1.4 Diabetes mellitus

1.7 stroke or

TIA

2.5

Fuster V, et al. J Am Coll Cardiol2006;48:e149‐e246. Gage BF, et al. JAMA2001;285:2864‐70

.



Outlines

prevention,

diagnosis,

&

treatment

of

thrombosis



Encompasses

many

clinical

conditions:

medical

surgery,

orthopedic

surgery,

atrial

fibrillation,

stroke,

cardiovascular

disease,

pregnancy,

children,

etc.



Includes

>

600 recommendations

in

>

800 pages

Antithrombotic Therapy and Prevention of Thrombosis, 9

th

_{ed: American}

College of Chest Physicians Evidence‐Based Clinical Practice Guidelines

Chapter

18:

Antithrombotic

Therapy

for

Atrial

Fibrillation

Guyatt GH, Akl EA, Crowther M, et al. Introduction to the ninth edition: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence‐Based Clinical Practice Guidelines. Chest. 2012;141(2 Suppl):48S‐52S.



Strong

– grade

1 

Weak

– grade

2 

High

quality

– A



Moderate

quality

– B



Low

quality

– C

Level

of

Evidence

(3)

Patients

included:



Permanent,

persistent,

or

paroxysmal

AF



Special

situations



Cardioversion

Antithrombotic Therapy and Prevention of Thrombosis, 9

th

_{ed: American}

College of Chest Physicians Evidence‐Based Clinical Practice Guidelines

Chapter

18:

Antithrombotic

Therapy

for

Atrial

Fibrillation

You JJ, Singer DE, Howard PA, et al. Antithrombotic therapy for atrial fibrillation: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence‐Based Clinical Practice Guidelines. Chest. 2012 Feb;141(2 Suppl):e531S‐75S.

Patients

NOT

included:



Pre

‐

&

postinvasive

procedures



Acute

stroke



Prosthetic

valve



Pregnant



Single,

isolated

episode

Decision

Pathway

Start here  Atrial fibrillation No mitral stenosis No CAD CHADS2= 0: No therapy CHADS2≥ 1: anticoagulation CAD Stable CAD CHADS2= 0: patient specific therapy CHADS2≥ 1: VKA monotherapy ACS w/n 12 mths To be continued… Mitral stenosis VKA therapy

Low

Risk

CHADS

2

=

0 Strength

Recommendation

No

therapy

>

Antithrombotic therapy

Grade

2B

Alternatives

Aspirin >

Oral

anticoagulation

Grade

2B

Aspirin

>

Aspirin

+

clopidogrel

Grade

2B

Data

for

Recommendation



ASA

use

for

1 year

compared

to

no

treatment

prevented

2 nonfatal

strokes

while

causing

3 nonfatal

major

extracranial bleeds

per

1000

patients



Use

of

VKA

therapy

compared

to

no

therapy

resulted

in

5 fewer

nonfatal

strokes

and

8 more

nonfatal

major

extracranial bleeds

per

1000

patients



Reduction

in

all

‐

cause

mortality

not

likely

to

extend

to

low

‐

risk

patients



Increased

risk

for

intracranial

hemorrhage

remains

similar

to

higher

‐

risk

patients



Oral

anticoagulation

may

be

favored

for

patients

with

multiple

non

‐

CHADS

2

risk

factors

for

stroke

(age

65 – 74,

female

sex,

vascular

disease,

etc.)

(4)

CHADS

2

=

1 Strength

Recommendation

Oral

anticoagulation*

>

No

therapy

Grade

1B

>

Aspirin

Grade

2B

>

Aspirin +

clopidogrel

Grade

2B

Alternative

(for

reasons

other

than

bleeding

concerns)

Aspirin +

clopidogrel >

Aspirin

Grade

2B

Intermediate

Risk

*Oral anticoagulation

Strength

Dabigatran 150mg

twice

daily

>

Warfarin

Grade

2B



Randomized,

multicenter,

prospective,

noninferiority trial

dabigatran 110

mg

bid

or

150 mg

bid

versus

warfarin

in

patients

with

nonvalvular AF

and

≥

1 of

the

following:



stroke

or

transient

ischemic

attack

(TIA)



Left

ventricular

ejection

fraction

(LVEF)

<

40%



CHF,

NYHA

class

≥

2 

Age

≥

75 yo



Age

65 ‐

74 yo with

DM,

CAD,

HTN



Primary

efficacy

outcome:

stroke

or

systemic

embolism



Primary

safety

outcome:

major

hemorrhage

Dabigatran versus

warfarin

in

patients

with

atrial

fibrillation

Randomized Evaluation of Long‐term anticoagulant therapY (RE‐LY) trial

Connolly SJ, Ezekowitz MD, Yusuf S, et al. Dabigatran versus warfarin in patients with atrial fibrillation. N Engl J Med. 2009;361(12):1139‐51

Results

listed

as

%

of

patients

per

year:

*p

<

0.05 compared

to

warfarin

**p

<

0.05 compared

to

dabigatran 150

mg

Dabigatran versus

warfarin

in

patients

with

atrial

fibrillation

Randomized Evaluation of Long‐term anticoagulant therapY (RE‐LY) trial

Connolly SJ, Ezekowitz MD, Yusuf S, et al. Dabigatran versus warfarin in patients with atrial fibrillation. N Engl J Med. 2009;361(12):1139‐51

Event

Warfarin

(n

=

6022)

Dabigatran 110

mg

(n

=

6015)

Dabigatran 150

mg

(n =

6076)

Stroke/systemic

embolism

1.69 1.53*

1.11*

Ischemic

stroke

1.2

1.34 0.92*

Hemorrhagic stroke

0.38 0.12*

0.1*

Major bleed

3.36 2.71*

3.11 Gastrointestinal

(GI)

bleed

1.02**

1.12

1.51 CHADS

2

≥

2 Strength

Recommendation

Oral anticoagulation*

>

No

therapy

Grade

1A

> Aspirin

Grade

1B

>

Aspirin

+

clopidogrel

Grade

1B

Alternative

(for

reasons

other

than bleeding

concerns)

Aspirin

+

clopidogrel >

Aspirin

Grade

1B

High

Risk

*Oral anticoagulation

Strength

Dabigatran 150mg

twice

daily

>

Warfarin

Grade

2B

(5)



VKA

therapy

compared

to

ASA

for

1 year

resulted

in

19 fewer

strokes

at

the

expense

of

3 more

bleeds

per

1000

patients



VKA

therapy

compared

to

ASA

+

clopidogrel for

1 year

resulted

in

11 fewer

strokes

and

up

to

3 more

bleeds

per

1000

patients



Dual

antiplatelet

therapy

is

inferior

as

compared

to

VKA

therapy

for

stroke

prevention

Data

for

Recommendation

You JJ, Singer DE, Howard PA, et al. Antithrombotic therapy for atrial fibrillation: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence‐Based Clinical Practice Guidelines. Chest. 2012 Feb;141(2 Suppl):e531S‐75S., ACTIVE Writing Group of the ACTIVE Investigators, Connolly S, Pogue J, Hart R, et al. 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 randomised controlled trial. Lancet. 2006 Jun 10;367(9526):1903‐12.



Which

of

the

following

has

been

shown

to

be

associated

with

an

increased

stroke

risk

that

is

identified

in

CHADS

2 ‐

VASc?



A)

Female

sex



B)

Age

55 – 74

yo



C)

Asian

race



D)

Valvular disease

Question



GB

is

a

67 yo female

with

atrial

fibrillation,

rhythm

controlled

with

amiodarone 200

mg

daily.

Her

PMH

is

significant

for

migraines,

gestational

DM,

and

endometriosis.

What

is

her

CHADS

2 score?



A)

0 

B)

1 

C)

2 

D)

3 Case



GB

is

a

67 yo female

atrial

fibrillation,

rhythm

controlled

with

amiodarone 200

mg

daily.

Her

PMH

is

significant

for

migraines,

gestational

DM,

and

endometriosis.

Based

on

GB’s

CHADS

2 score,

what

is

the

antithrombotic

therapy?



A)

no

pharmacological

agent



B)

aspirin

75 mg

– 325

mg

daily



C)

dose

adjusted

warfarin

with

goal

INR

2 – 3



D)

aspirin

75 mg

– 325

mg

daily

+

clopidogrel 75

mg

daily

(6)

Special

Situations

Decision

Pathway

ACS w/n 12 mths No stent placement CHADS2= 0: dual antiplatelet therapy x 12 mths CHADS2≥ 1: VKA therapy + antiplatelet x 12 mths Stent placement Bare metal CHADS2≤ 1: ASA + clopidogrel x 12 mths CHADS2≥ 2: triple therapy x 1 mth VKA therapy + antiplatelet x 2nd– 12thmth Drug‐eluting CHADS2≤ 1: ASA + clopidogrel x 12 mths CHADS2≥ 2: triple therapy x 3 – 6 mths VKA therapy + antiplatelet x > 3 – 6 mths – 12thmth

Reassess antithrombotic therapy needs after completion of 12 mths = Stable CAD

CHADS

2

≥

0 Strength

Recommendation

Oral anticoagulation*

>

No

therapy

Grade

1B

>

Aspirin

Grade

1B

>

Aspirin

+

clopidogrel

Grade

1B

Alternative

(for

reasons

other

than

bleeding concerns)

Aspirin +

clopidogrel >

Aspirin

Grade 1B

AF

+

Mitral

Stenosis

*Oral anticoagulation

Warfarin

AF

+

Stable

Coronary

Artery

Disease

CHADS

2

≥

0 Strength

Recommendation

Warfarin>

Warfarin +

aspirin

Grace

2C



Patients with coronary artery disease (CAD) are recommended to

use ASA for prevention of cardiovascular events



1/3 of AF patients have CAD

(7)

AF

+

Non

‐

invasive

ACS

CHADS

2

≥

1 Strength

Recommendation

First

12 months

after ACS

Warfarin +

antiplatelet

agent

>

Aspirin

+

clopidogrel

Grace

2C

>

Warfarin

+

aspirin

+

clopidogrel

Grade

2C

>

12 months

after

ACS*

Warfarin

>

Warfarin +

aspirin

Grace

2C

*same

recommendation

as

“AF

+

Stable

CAD”

CHADS

2

=

0 – 1

Strength

Recommendation

First

12 months

post bare

metal

OR

drug

‐

eluting

Aspirin +

clopidogrel

>

Warfarin

+

aspirin

+

clopidogrel

Grade

2C

> Warfarin

+

aspirin

Grade 2C

>

12 months*

Warfarin

> Warfarin

+ aspirin

Grade

2C

Low

or

Intermediate

Risk

+

Stent

*same

recommendation

as

“AF

+

Stable

CAD”

CHADS

2

≥

2 Strength

Recommendation

Bare metal:

1

st

_month

_Drug

_‐

_{eluting: First}

₃

_{– 6}

_months

Warfarin

+

aspirin +

clopidogrel

>

Aspirin

+

clopidogrel

Grade

2C

Bare

metal:

2

nd

_{– 12}

th

_month

_Drug

_‐

_eluting:

_>

₃

_‐

₆

_months

_{– 12}

th

_month

Warfarin +

antiplatelet

agent

>

Warfarin

Grade

2C

Bare

metal:

>

12 months*

Drug

‐

eluting:

>

12 months*

Warfarin

>

Warfarin

+

aspirin

Grade

2C

High

Risk

+

Stent

*same

recommendation

as

“AF

+

Stable

CAD”

AF

>

48 hours

Strength

Recommendation

Before

scheduled

cardioversion

Warfarin, LMWH,

or

dabigatran x

3 weeks

>

No

therapy

1B

After

successful

cardioversion

Warfarin, LMWH,

or

dabigatran x

4 weeks

>

No

therapy

1B

AF

+

Elective

Cardioversion

AF

≤

48 hours

Strength

Recommendation

Before

cardioversion

LMWH

or

UFH

>

Delaying 3

weeks

for

anticoagulation

2C

After

successful

cardioversion

Warfarin, LMWH,

or

dabigatran x

4 weeks

>

No

therapy

2C

(8)

Strength

Recommendation

Before

cardioversion

Parenteral

anticoagulation

> No

therapy*

2C

After

successful

cardioversion

Warfarin, LMWH,

or

dabigatran x

4 weeks

>

No

therapy

2C

AF

+

Immediate

Cardioversion

*do

not

delay

intervention

for

initiation

of

anticoagulation



LW

is

a

78 yo female

with

atrial

fibrillation,

rate

controlled

with

metoprolol tartrate

25 mg

bid.

Her

PMH

is

significant

for

hypertension,

MI

in

2008,

and

asthma.

Based

on

LW’s

CHADS

2 score,

what

is

the

antithrombotic

therapy?



A)

aspirin

75 mg

– 325

mg

daily



B)

dose

adjusted

warfarin

with

goal

INR

2 – 3



C)

aspirin

75 mg

– 325

mg

daily

+

clopidogrel 75

mg

daily



D)

dabigatran 150

mg

twice

daily

Case



If

LW’s

MI

was

11/12

with bare

metal

stenting,

would

the

recommendation

change?



A)

Yes,

dose

adjusted

warfarin

with

goal

INR

2 – 3

+

aspirin

75 mg

– 325

mg

daily

+

clopidogrel 75

mg

daily



B)

Yes,

dose

adjusted

warfarin

with

goal

INR

2 – 3

+

aspirin

75 mg

– 325

mg

daily

OR

dose

adjusted

warfarin

with

goal

INR

2 – 3

+

clopidogrel 75

mg

daily



C)

No



D)

Yes,

dabigatran 150

mg

twice

daily

+

aspirin

75 mg

– 325

mg

daily

Case,

part

2

(9)

The

Ideal

Anticoagulant

Oral

Once

daily

dosing

Quick

onset

Minimal

monitoring

Minimal

drug

interactions

Available

and

effective

antidote

Wide

therapeutic

index

Low

cost



FDA

Indications

:



Postoperative

thromboprophylaxis



Treatment

of

deep

vein

thrombosis

(DVT)

&

pulmonary

embolism

(PE)



Prevention

of

stroke

&

systemic

embolism

in

nonvalvular AF



Dose:

20 mg

daily

with

evening

meal



Pharmacokinetics

:



Absorption:

bioavailability

80 ‐

100%,

take

with

food

for

AF

indication



Metabolism

:

P

‐

glycoprotein,

CYP3A4

substrate



Elimination

:

half

‐

life

of

5 ‐

9 h,

11 ‐

13 h

(elderly);

66%

(renal),

34%

(feces)



Avoid

use

in

CrCl <

15 mL/min



Dose

reduction

for

CrCl 15

– 50

mL/min

Rivaroxaban (Xarelto®)

Direct Factor Xa inhibitor

Rivaroxaban. Clinical Pharmacology. Retreived Jan 5, 2013 from clinicalpharmacology.com



Contraindications/Warnings

:



Box

Warnings:



Neuraxial anesthesia

or

spinal

puncture



Discontinuation

of

therapy



Hepatic

disease



Active

bleeding



Concomitant

use

with

strong

CYP3A4

or

P

‐

glycoprotein

inhibitors/inducers



Monitoring:

routine

monitoring

not

required



Anti

‐

factor

Xa

‐

no

therapeutic

level

has

been

established



Prothrombin time

(PT)/

INR

‐

dose

dependent

with

PT;

INR

is

standardized

for

warfarin



Activated

partial

thromboplastin time

(aPTT)

‐

not

effective,

prolongation

only

seen

at

peak

drug

levels

Rivaroxaban (Xarelto®)

Direct Factor Xa inhibitor

Rivaroxaban. Clinical Pharmacology. Retreived Jan 5, 2013 from clinicalpharmacology.com

Rivaroxaban (Xarelto®)

Direct Factor Xa inhibitor



Common

adverse

effects

:



Bleeding

(hip/knee

replacement

5.8%

)



Serious

adverse

effects

:



Syncope

(1.2%

)



GI

hemorrhage

(3.1%

)



Major

bleeding (a

‐

fib

5.6%;

hip/knee

0.3%

)



Epidural/spinal

hematoma



Anaphylaxis



Cerebrovascular

accident



Patient

Instructions:



Do

not

miss

doses



Take

with

evening

meal

Rivaroxaban. Clinical Pharmacology. Retreived Jan 5, 2013 from clinicalpharmacology.com, http://www.focalpharmacy.com/index.php?main_page=product_info&products_id=13

(10)



Randomized,

multicenter,

double

‐

blind,

double

‐

dummy,

prospective,

noninferior trial

of

rivaroxaban 20

mg

daily

vs warfarin

in

patients

with

nonvalvular AF

& history

of

stroke,

TIA,

or

systemic

embolism

or

≥

2 of

the

following:



LVEF

≤

35%

or

CHF



HTN



Age

≥

75 yo



DM



Primary

efficacy

outcome:

stroke

or

systemic

embolism



Primary

safety

outcome:

major

or

nonmajor clinically

relevant

bleeding

events

Rivaroxaban versus

warfarin

in

nonvalvular atrial

fibrillation

Rivaroxaban Once

daily

oral

direct

factor

Xa inhibition

Compared

with

vitamin

K

antagonism

for

prevention

of

stroke

and

Embolism

Trial

in

Atrial

Fibrillation

(ROCKET

AF)

Patel MR, Mahaffey KW, Garg J, Pan G, et al. Rivaroxaban versus warfarin in nonvalvular atrial fibrillation. N Engl J Med. 2011;365(10):883‐91

Results

listed

as

number

of

events

per

100 patient

‐

years:

*p

<

0.05 compared

to

warfarin

**p

<

0.05 compared

to

rivaroxaban

Rivaroxaban versus

warfarin

in

nonvalvular atrial

fibrillation

Rivaroxaban Once

daily

oral

direct

factor

Xa inhibition

Compared

with

vitamin

K

antagonism

for

prevention

of

stroke

and

Embolism

Trial

in

Atrial

Fibrillation

(ROCKET

AF)

Patel MR, Mahaffey KW, Garg J, Pan G, et al. Rivaroxaban versus warfarin in nonvalvular atrial fibrillation. N Engl J Med. 2011;365(10):883‐91

Events

Warfarin

(n

=

7004)

Rivaroxaban (n

=

6958)

Stroke/systemic

embolism

2.2 1.7*

Ischemic

stroke

1.42

1.34 Hemorrhagic stroke

0.44 0.26*

Major bleed

14.5

14.9 GI

bleed

(listed

as

%)

2.16**

3.15 

FDA

indications

:



Postoperative

thromboprophylaxis



Prevention

of

stroke

& systemic

embolism

in

nonvalvular AF



Dose:

150 mg

twice

daily



Pharmacokinetics

:



Absorption

:

bioavailability

3 ‐

7%;

take

with

or

without

food



Metabolism

:

P

‐

glycoprotein;

converted

to

active

moiety

by

esterase

‐

catalyzed

hydrolysis



Elimination

:

half

‐

life

of

12 ‐

17 h;

80%

(renal)



Avoid

use

in

CrCl <

15 mL/min



Dose

reduction

for

CrCl 15

– 30

mL/min

Dabigatran (Pradaxa®)

Direct

thrombin

inhibitor

Dabigatran. Clinical Pharmacology. Retreived Jan 5, 2013 from clinicalpharmacology.com



Contraindications/Warnings:



Active

bleeding



Prosthetic

heart

valve



Elderly

population



Discontinuation

of

therapy



Concomitant

use

with

strong

P

‐

glycoprotein

inhibitors/inducers



Monitoring:

routine

monitoring

not

required



aPTT

‐

value

2.5 x

normal

may

indicate

over

anticoagulation

Dabigatran (Pradaxa®)

Direct

thrombin

inhibitor

(11)



Common

adverse

effects:



Esophagitis,

GERD,

GI

hemorrhage

(6.1%

)



Bleeding

(16.6%

)



Serious

adverse

effects:



Major

GI

hemorrhage

(1.6%

)



Life

‐

threatening

bleeding

(1.5%

)



Major

bleeding

(3.3%

)



Anaphylaxis

(<

0.1%

)



Intracranial

hemorrhage

(0.3%

)

Dabigatran (Pradaxa®)

Direct

thrombin

inhibitor

Dabigatran. Clinical Pharmacology. Retreived Jan 5, 2013 from clinicalpharmacology.com



Patient

instructions:



Do not miss doses



Do not break capsule



Keep medication in original bottle



Discard medication 120 days after opening bottle

Dabigatran (Pradaxa®)

Direct

thrombin

inhibitor

Dabigatran. Clinical Pharmacology. Retrieved Jan 5, 2013 from clinical pharmacology.com,

http://keepyourhearthealthy.wordpress.com/tag/dabigatran/



FDA

approved

indication:



Prevention

of

stroke

or

systemic

embolism

in

nonvalvular AF



Dose:

5 mg

twice

daily



2.5 mg

twice

daily

if

≥

2 of

the

following:

age

≥

80 yo,

weight

≤

60 kg,

SCr

≥

1.5 mg/dL



Pharmacokinetics:



Absorption

:

bioavailability

~50%;

take

with

or

without

food



Metabolism

:

P

‐

glycoprotein;

CYP3A4

substrate

(minor)



Elimination

:

half

‐

life

12 h;

25%

(renal),

55%

(feces)



Avoid

use

in

CrCl <

15 mL/min

Apixaban (Eliquis®)

Direct Factor Xa inhibitor

Apixaban. Clinical Pharmacology. Retreived Jan 5, 2013 from clinicalpharmacology.com



Contraindications/Warnings:



Active

bleeding



Prosthetic

heart

valve



Hepatic

disease



Body

weight

<

50 kg

or

>

120 kg



Neuraxial anesthesia



Monitoring:

routine

monitoring

not

required



PT/INR

‐

prolonged



aPTT

‐

prolonged



Anti

‐

factor

Xa

‐

linear

relationship

with

plasma

concentrations

Apixaban (Eliquis®)

Direct Factor Xa inhibitor

(12)



Common

adverse

effects:



Bleeding

(6%)



Nausea

(7%)



Vomiting

(5%)



Constipation

(5%)



Serious

adverse

effects:



Major

bleeding

(2.1%

)



Anaphylaxis

(<

1%

)



Intracranial

hemorrhage

(0.3%

)

Apixaban (Eliquis®)

Direct Factor Xa inhibitor

Apixaban. Clinical Pharmacology. Retrieved Jan 5, 2013 from clinicalpharmacology.com, http://www.dicardiology.com/article/fda‐receives‐ resubmission‐apixaban‐drug‐application‐reduce‐stroke‐patients‐atrial‐fibrillati



Patient

Instructions:



Do

not

miss

doses



Randomized,

multicenter,

double

‐

blind,

double

‐

dummy,

prospective,

noninferior trial

of

apixaban 5

mg

bid

vs warfarin

in

patients

with

nonvalvular AF

and

≥

1 of

the

following:



stroke,

TIA,

or

systemic

embolism



LVEF

≤

40%

or

symptomatic

CHF

w/n

3mos



HTN

requiring

medication

management



Age

≥

75 yo



DM



Primary

efficacy

outcome:

stroke

or

systemic

embolism



Primary

safety

outcome:

major

bleed

Apixaban versus

warfain in

patients

with

atrial

fibrillation

Apixaban for

Reduction

In

STroke and

Other

ThromboemboLic Events

in

atrial

fibrillation

trial

(ARISTOTLE)

Granger CB, Alexander JH, McMurray JJ, Lopes RD, et al. Apixaban versus warfarin in patients with atrial fibrillation. N Engl J Med. 2011;365(11):981‐92

Results

listed

as

%

of

patients

per

year:

*p

<

0.05 compared

to

warfarin

Apixaban versus

warfain in

patients

with

atrial

fibrillation

Apixaban for

Reduction

In

STroke and

Other

ThromboemboLic Events

in

atrial

fibrillation

trial

(ARISTOTLE)

Granger CB, Alexander JH, McMurray JJ, Lopes RD, et al. Apixaban versus warfarin in patients with atrial fibrillation. N Engl J Med. 2011;365(11):981‐92

Events

Warfarin

(n

=

9081)

Apixaban (n

=

9120)

Stroke/systemic

embolism

1.6 1.27*

Ischemic

stroke

1.05

0.97 Hemorrhagic stroke

0.47 0.24*

Major bleed

3.09 2.13*

GI

bleed

0.86

0.76 

Which

of

the

new

oral

anticoagulants

must

be

taken

with

food?



A)

Rivaroxaban



B)

Dabigatran



C)

Apixaban



D)

All

of

the

above

(13)



Dabigatran should

be

dispensed

in

the

original

bottle

and

should

be

discarded

after

how

many

months?



A)

1 

B)

2 

C)

3 

D)

4 Question

Comparison

of

Oral

Anticoagulants

Rivaroxaban. Clinical Pharmacology. Retreived Jan 5, 2013 from clinicalpharmacology.com, Dabigatran. Clinical Pharmacology. Retreived Jan 5, 2013 from clinicalpharmacology.com, Apixaban. Clinical Pharmacology. Retreived Jan 5, 2013 from clinicalpharmacology.com