Answering the Call: The Role of Health-System Pharmacists ...Answering the Call: The Role of...

Answering the Call: The Role of Health-System Pharmacists to Improve Use of

Target-Specific Oral Anticoagulants

© 2014 Paradigm Medical Communications, LLC, except where noted. All rights reserved.

1

Faculty

Sarah A. Spinler, PharmD, FCCP,

FCPP, FAHA, FASHP, AACC, BCPS

AQ–Cardiology (Chair)

Professor of Clinical Pharmacy

Philadelphia College of Pharmacy

University of the Sciences

Philadelphia, PA

John Fanikos, RPh, MBA

Director of Pharmacy, Business

Brigham and Women’s Hospital

Boston, MA

Denise H. Rhoney, PharmD, FCCP,

FCCM, FNCS

Ron and Nancy McFarlane

Distinguished Professor and Chair

Division of Practice Advancement

and Clinical Education

UNC Eshelman School of Pharmacy

Chapel Hill, NC




2

Agenda

• Welcome and Opportunities for Clinical Pharmacy Action

• Balancing Act: Risk Assessment in Anticoagulation Management

• Clinical Pharmacology of TSOAs: What's Important to Know

• Oral Anticoagulation use in Stroke Prevention in Atrial Fibrillation

• Oral Anticoagulation use in Deep Vein Thrombosis and Pulmonary Embolism

• Addressing Clinical Challenges: Focus on Coagulation Monitoring and Management of Bleeding

• Clinical Pharmacy Call to Action: Ensuring Appropriate Anticoagulation

• Panel Discussion/Interactive Case Review

Welcome and Opportunities for Clinical Pharmacy Action

Sarah Spinler, PharmD, FCCP, FCPP, FAHA, FASHP, AACC,BCPS–AQ Cardiology




3

The Impact of Atrial Fibrillation

• AF will affect ≈6 million

Americans by 20501

• >70% is NVAF

• Leads to 100,000–125,000

embolic strokes/y2

• AF related stroke leads to2:

• Chronic disability

• Bedridden patients

• Constant nursing care

• >20% are fatal

1. Ciervo CA et al. J Am Osteopath Assoc. 2012;112:eS2-eS8. 2. Reiffel JA. Am J Med. 2014;127:e15-e16.

Republished with Permission of Am Osteopathic Assoc, from Ciervo CA et al, Stroke prevention in patients with atrial fibrillation: disease burden and

unmet medical needs, J Am Osteopath Assoc, 2012;112(9 Suppl 2):eS2-eS8; permission conveyed through Copyright Clearance Center.

AF, atrial fibrillation; NVAF, nonvalvular atrial fibrillation

The Impact of Venous Thromboembolism

• > 1 million pts worldwide have unprovoked VTE each year1

• VTE affects up to 900,000 people/y in US1,2

• 1/2 will have long-term complications

• Up to 1/3 will die within 1 mo of diagnosis

• Up to 1/3 will have a recurrence within 10 y

• PE • Leading preventable cause of death in hospitalized patients3

• Sudden death is 1st symptom in 1/4 of patients1

• Mortality rate without treatment ≈30%4

(vs 8% with adequate treatment )

1. Simes J et al. Circulation. 2014;130:1062-1071. 2. Raskob GE et al. Am J Prev Med. 2010;38(4 Suppl):S502-S509. 3. Walter RJ et al. Curr Med

Res Opin. 2014;30(10):1975-1989. 4. Carson JL et al. N Engl J Med 1992;326(19):1240-1245.

MI, myocardial infarction; PE, pulmonary embolism; VTE, venous thromboembolism




4

Opportunities to Achieve Appropriate Anticoagulation

• 57% of patients with NVAF at high risk for stroke receive guideline-recommended anticoagulation1

• 1/3 of AF patients are not on anticoagulation but only 12% have contraindications2

• TTR on VKAs increases from 30%-60% with usual care to up to 60%–90% with anticoagulation management3

• ≈40% of patients taking OACs + aspirin had no documented indication for aspirin4

• Less than half of those with unprovoked VTE remain on long-term anticoagulation5

1. Jacobovitz S. J Am Coll Cardiol. 2014;64:226-228. 2. ACCEL: Probing the ORBIT-AF Registry. www.cardiosource.org/en/News-

Media/Publications/CardioSource-World-News/2013/October/ACCEL-Probing-the-ORBIT-AF-Registry.aspx/ . Accessed July 3, 2014. 3. Ansell JA.

http://excellence.acforum.org/sites/default/files/Patient%20Self%20Testing%20Presentation.pdf. Accessed July 14, 2014. 4. Steinberg BA et al; for the

ORBIT-AF Investigators and Patients. Circulation. 2013;128:721-728. 5. Simes J et al. Circulation. 2014;130:1062-1071.

ORBIT AF, Outcomes Registry for Better Informed Treatment of Atrial Fibrillation; OAC, oral anticoagulant; TTR, time in

therapeutic range; VKAs, vitamin K antagonists

There are clear opportunities for clinical pharmacists to take

an active role to improve anticoagulation management!

Balancing Act: Risk Assessment in Anticoagulation Management




5

BleedingThrombosis

An ideal anticoagulant will provide the greatest reduction

in thromboembolism with the lowest incidence of bleeding.

1. Camm JA et al. Eur Heart J. 2012;33:2719-2747. 2. Ansell J et al. Chest. 2001;119:22S-38S. 3. Fuster V et al. J Am Coll Cardiol. 2001;38:1231-1266.

• Assess bleeding risk1,2

• Identify “red flags”2

• Control modifiable

risk factors2

• Select appropriate

anticoagulant2,3

• Dosage adjustment2,3

• Monitoring/adherence3

• Drug-drug interactions3

• Assess stroke risk1

• Control modifiable

risk factors2

• Evidence-based

anticoagulant regimen2,3

• Monitoring/adherence

• Drug-drug interactions2,3

Optimize Benefits, Minimize Risk

Goal of Anticoagulation Therapy

Risk Factor Score

C Congestive heart failure/LVEF ≤40% /1

H Hypertension /1

A2 Age ≥75 /2

D Diabetes mellitus /1

S2 Previous history of stroke, TIA, TE /2

V

Vascular disease, including prior MI,

peripheral artery disease, aortic

plaque

/1

A Age 65–74 /1

Sc Sex category = female /1

Total score /9

Risk Factor Score

H Hypertension* /1

AAbnormal renal or liver function

(1 point each)/2

S Previous history of stroke /1

BBleeding history or disposition

(anemia)/1

L Labile INRs /1

E Elderly: age >65 /1

DDrugs (antiplatelets or NSAIDs) or

alcohol (1 point each)/2

Total score /9

Assess Stroke Risk: CHA2DS2-VASc1,2 Assess Bleed Risk: HAS-BLED1,3

*Hypertension refers to uncontrolled hypertension

LVEF, left ventricular ejection fraction; TIA, transient ischemic attack; TE, thromboembolic event

Clinical Decision Aid: SPAF

1. Lahaye S et al. Thromb Haemost. 2014;111(3):465-473; online Suppl 2: 111.4. 2. Lip GYH, et al. Chest. 2010; 137: 263-272.3. Pisters R et al. Chest.

2010; 138: 1093-1100. Reproduced with permission from the American College of Chest Physicians.




6

American College of Cardiology AnticoagEvaluator App for AF

Easy, fast way to assess stroke and bleeding risk and benefits vs risks of antithrombotic therapy

• Combination risk calculator uses CHADS2, CHA2DS2-VASc, HAS-BLED

• Enter patient characteristics at POC; get individualized annual risk of ischemic stroke, thromboembolism with concurrent annual risk of major bleed

• Compare antithrombotic therapy options based on clinical trials (ACTIVE-A, RE-LY, ROCKET-AF, ARISTOTLE)

Available at: https://itunes.apple.com/us/app/anticoagevaluator/id609795286?mt=8. Accessed 11/17/14. Available at:

https://play.google.com/store/apps/details?id=org.acc.AnticoagEvaluator&hl=en. Accessed 11/17/14.

POC, point of care

• Goal: Determine best anticoagulation strategy for individual

patient

• Stroke risk assessment using CHA2DS2-VASc• Most patients with CHA2DS2-VASc score >1 will derive net benefit from

well-managed anticoagulation, irrespective of bleeding risk score

• Patients with low CHA2DS2-VASc score and/or very high bleeding risk

may not be candidates for antithrombotic therapy (cases will be rare)

• Bleeding risk assessment: Performed only to identify

modifiable risk factors for bleeding

• HAS-BLED score NOT recommended (low C-statistic)

• Shared decision making: risk factors, cost, tolerability, patient preference, drug interaction potential, TTR if warfarin

AHA/ACC/HRS Recommendations for Objective Risk Assessment

AHA, American Heart Association; ACC, American College of Cardiology; HRS, Heart Rhythm Society; TTR, time to

response

January CT et al. J Am Coll Cardiol. 2014 Mar 28. pii: S0735-1097(14)01740-9.




7

Risk Factors Risk Measure 95% CI

Patient Features

- Age (per decade increase)

- Male sex

HR = 1.17

HR = 1.56

1.11 – 1.24

1.22 – 2.00

Index Event

- PE

- Isolated distal DVT

HR = 1.19

HR = 0.49

0.87 – 1.63

0.34 – 0.71

Risk Factors

- Surgery

- Trauma-associated VTE*

HR = 0.36

HR = 0.51

0.21 – 0.62

0.32 – 0.87

Residual DVT

- Overall population

- Unprovoked VTE

OR = 1.50

OR = 1.24

1.11 – 2.03

0.90 – 1.71

Increased D-dimer OR = 2.36 1.65 – 3.36

*Compared with unprovoked VTE

Risk Factors for Recurrent VTE with Relative Strength of Association

Agnelli G et al. American Society of Hematology Education Book. 2013;1:471-477. Republished with permission of American Society of Hematology;

permission conveyed through Copyright Clearance Center, Inc.

CI, confidence interval; DVT, deep venous thrombosis; VTE, venous thromboembolism; OR, odds ratio; HR, hazard

ratio; PE, pulmonary embolism

Key Points

• Understand the personal and fiscal impact of stroke and DVT/VTE/PE

• Balanced risk assessment is important to• Identify patients at risk

• Help in treatment selection and planning

• In NVAF• CHA2DS2-VASc is recommended

• Bleeding risk assessment to identify modifiable risk factors

• In VTE• Few available tools

• Evaluate risk factors for recurrent VTE and consider bleeding risks




8

Clinical Pharmacology: What’s Important to Know

Denise Rhoney, PharmD, FCCP,FCCM, FNCS

Dabigatran1 Rivaroxaban2 Apixaban3 Edoxaban4-8

Drug classDirect factor IIa

inhibitorDirect factor Xa inhibitor

Direct factor Xa

inhibitor

Direct factor Xa

inhibitor

Time to Cmax 1 h 2-4 h 3-4 h 1-2 h

CYP metabolism None

CYP3A4/5, CYP2J2, and

hydrolysis are the major

means of

biotransformation

Mainly by

CYP3A4

62% fecal

elimination

Renal excretion80% of absorbed

dose

66% of total dose; 36% as

unchanged drug27% 35% of total dose

Protein binding 35% 92%-95% 87% 40%–59%

Half-life 12-17 h 5-9 h ≈12 h

6–11 h4,5

9–11 h6

10–14 h8

Dosing frequency

NVAFBID QDay BID QDay

1. Pradaxa (dabigatran etexilate mesylate) [prescribing information]. Ridgefield, CT: Boehringer Ingelheim Pharmaceuticals Inc.; 9/2014.

2. Xarelto (rivaroxaban) [prescribing information]. Titusville, NJ: Janssen Pharmaceuticals, Inc.; 9/2014. 3. Eliquis (apixaban) [prescribing information].

Princeton, NJ: Bristol-Myers Squibb Company; 8/2014. 4. Camm AJ et al. Drugs. 2011;71:1503-1526. 5. Ogata K et al. J Clin Pharmacol. 2010;50:743-

753. 6. Eikelboom JW et al. Circulation. 2010;121:1523-1532. 7. Bathala M et al. Drug Metab Dispos. 2012;40:2250-2255. 8. Bounameaux H et al.

Drugs. 2014;74:1209-1231.

TSOAs: Pharmacology

Cmax, time to maximum concentration; PK/PD, pharmacokinetics/pharmacodynamics




9

TSOAs: Dosing

Dabigatran1 Rivaroxaban2,3,4 Apixaban5 Edoxaban6,7

Formulation

Issues

• CANNOT crush

capsules

• Expires 4 mo

after bottle is

opened

• CAN crush

• Mix with applesauce;

for patients with

feeding tube, mix

with water

• CAN crush

• Mix with water and

give via feeding

tube

• No information

Food

Effects5

• Take with or w/o

food

• 10-mg tablet*: take

with or w/o food

• 15-mg and 20-mg

tablets: Take with

largest meal of the

day

• Bioavailability not

affected by food

• Can be

administered

without regard

to food

1. Pradaxa [package insert]. Ridgefield, CT: Boehringer Ingelheim Pharmaceuticals Inc.; 2014. 2. Xarelto [package insert]. Titusville, NJ: Janssen

Pharmaceuticals, Inc.; 2014. 3. Moore KT et al. Pharmacotherapy. 2012;32:e185. 4. Kubitza D et al. J Clin Pharmacol. 2006;46:549-558. 5. Eliquis

[package insert]. Princeton, NJ: Bristol-Myers Squibb Company; 8/2014. 6. Matsushima N et al. Clin Pharmacol Drug Dev. 2013;2:358-366. 7. Mendell

J et al. J Clin Pharmacol. 2011;51:687-694.

*Not FDA approved for AF

AUC, area under the curve; GI, gastrointestinal

TSOAs: Drug-Drug Interactions

Drug Interactions/Recommendations

Dabigatran1

NVAF

• P-gp inducers (rifampin) reduce exposure to dabigatran – avoid

• Use with P-gp inhibitors in impaired renal function increases exposure

• Concomitant use of dronedarone or systemic ketoconazole:

- CrCl 30-50 mL/min–reduce dose of dabigatran to 75 mg po BID

- CrCl 15-30 mL/min–avoid use of dabigatran

Treatment and prevention of VTE/PE

• Avoid dabigatran with P-gp inhibitors if CrCl <50 mL/min

Rivaroxaban2

• Combined P-gp and CYP3A4 inhibitors (ketoconazole, ritonavir, clarithromycin,

erythromycin and fluconazole) - significant increase in rivaroxaban exposure

may increase bleeding risk

• Coadministration with a combined P-gp and strong CYP3A4 inducer (e.g.,

rifampicin, phenytoin) may decrease efficacy

• Avoid concomitant use with combined P-gp and strong CYP3A4 inducers (e.g.,

carbamazepine, phenytoin, rifampin, St. John’s wort)

• Anticoagulants – avoid concomitant use

• Aspirin, NSAIDS – may increase bleeding risk

1. Pradaxa (dabigatran etexilate mesylate) [prescribing information]. Ridgefield, CT: Boehringer Ingelheim Pharmaceuticals Inc; 9/2014. 2. Xarelto

(rivaroxaban) [prescribing information]. Titusville, NJ: Janssen Pharmaceuticals, Inc; 9/2014

CrCl, creatinine clearance




10

TSOAs: Drug-Drug Interactions

Drug Interactions/Recommendations

Apixaban1• Strong dual inhibitors of CYP3A4 and P-gp (ketoconazole, itraconazole,

ritonavir, or clarithromycin) increase blood levels of apixaban–for

patients on doses greater than 2.5 mg BID, reduce the dose by 50%; if

on 2.5 mg BID avoid concomitant use

• Simultaneous use of strong dual inducers of CYP3A4 and P-gp

(rifampin, carbamazepine, phenytoin, St. John’s wort) reduces blood

levels of apixaban–avoid concomitant use

Edoxaban2• Concomitant use of potent P-gp inhibitors (quinidine, verapamil,

dronedarone)–halve dose of edoxaban

1. Eliquis (apixaban) [prescribing information]. Princeton, NJ: Bristol-Myers Squibb Co; 8/2014. 2. Giugliano RP et al. N Engl J Med. 2013; 369:2093-

2104.

CrCl, creatinine clearance

*For dabigatran, rivaroxaban, edoxaban, patients with CrCl <30 mL/min were excluded from clinical trials; for

apixaban, patients with CrCl <25 mL/min were excluded †The 75-mg dose of dabigatran was not evaluated in clinical trials, but is an FDA-approved dose‡Dose used in clinical trials

ESRD, end stage renal disease

Drug*† Dose

Dabigatran1

• CrCl >30 mL/min: 150 mg orally BID

• CrCl 15-30 mL/min: 75 mg orally BID†

• CrCl <15 mL/min or on dialysis: dosing recommendations cannot be provided

• Dronedarone or ketoconazole in patients with CrCl 30-50 mL/min: consider reducing dose to

75 mg bid or avoid use

• P-gp inhibitors in patients with CrCl <30 mL/min: not recommended

Rivaroxaban2

• CrCl >50 mL/min: 20 mg orally QDay

• CrCl 15-50 mL/min: 15 mg orally QDay

• CrCl <15 mL/min: not recommended

Apixaban3

• 5 mg orally BID

• 5 mg orally BID in patients with NVAF and ESRD maintained on hemodialysis

• Dose adjusted to 2.5 mg orally BID for patients with ≥2 of the following: age ≥80 y, weight ≤60

kg, or SCr ≥1.5 mg/dL

Edoxaban4‡• Both doses (30 mg and 60 mg) halved if CrCl 30-50 mL/min, body weight ≤60 kg, or taking

concomitant verapamil, quinidine, or dronedarone

• Patients with CrCL <30 mL/min were excluded from ENGAGE-AF TIMI 48

TSOA: Dosing for SPAF

1. Pradaxa (dabigatran etexilate mesylate) [prescribing information]. Ridgefield, CT: Boehringer Ingelheim Pharmaceuticals Inc; 9/2014. 2. Xarelto

(rivaroxaban) [prescribing information]. Titusville, NJ: Janssen Pharmaceuticals, Inc; 9/2014. 3. Eliquis (apixaban) [prescribing information]. Princeton,

NJ: Bristol-Myers Squibb Co; 8/2014. 4. Giugliano RP et al. N Engl J Med. 2013;369:2093-2104.




11

Drug* Dose

Dabigatran1

Treatment and reduction in the risk of recurrence of DVT and PE

• CrCl >30 mL/min, 150 mg orally BID after 5-10 d of parenteral anticoagulation

• CrCl < 30 mL/min or on dialysis, dosing recommendations cannot be provided

• CrCl <50 mL/min with a P-gp inhibitor, avoid use

Rivaroxaban2

Treatment of DVT, PE, and reduction in the risk of recurrence of DVT and PE

• Take 15-mg and 20-mg tablets with food; take 10-mg tablets with or without food

• 15 mg orally BID with food for the first 21 d for initial treatment of acute DVT or

PE; after the initial treatment period 20 mg orally QDay with food for remaining

treatment and long-term reduction in the risk for recurrence of DVT or PE

• 10 mg orally QDay with or without food to prevent DVT following hip or knee

replacement surgery

• CrCl <30 mL/min, avoid use

• Hip replacement surgery: recommended duration is 35 d

• Knee replacement surgery: recommended duration is 12 d

TSOA: Dosing for Recurrent DVT and PE

1. Pradaxa (dabigatran etexilate mesylate) [prescribing information]. Ridgefield, CT: Boehringer Ingelheim Pharmaceuticals Inc; 9/2014.

2. Xarelto (rivaroxaban) [prescribing information]. Titusville, NJ: Janssen Pharmaceuticals, Inc; 9/2014.

*Patients with CrCl <30 mL/min were excluded from all trials

Drug* Dose

Apixaban1

Treatment of DVT, PE, reduction in risk of recurrent DVT and PE following 6 mo of

initial therapy; prophylaxis of DVT following hip or knee replacement surgery

• 10 mg orally BID for 7 d, followed by 5 mg BID for treatment of DVT, PE

• 2.5 mg BID to prevent DVT following surgery; initial dose should be taken 12-24 h

after surgery

• 2.5 mg BID to reduce risk of recurrent DVT, PE after initial therapy

• Hip replacement surgery: recommended duration is 35 d

• Knee replacement surgery: recommended duration is 12 d

Edoxaban2†

Treatment and prevention of recurrence of VTE

• 60 mg orally QDay, taken with or without food

• 30 mg orally QDay (CrCl 30 to 50 mL/min or a body weight of 60 kg or less or in

patients who were receiving concomitant treatment with potent P-gp inhibitors)

1. Eliquis (apixaban) [prescribing information]. Princeton, NJ: Bristol-Myers Squibb Co; 8/2014. 2. Büller HR et al; Hokusai-VTE Investigators. N Engl J

Med. 2013;369:1406-1415.

TSOA: Dosing for Recurrent DVT and PE (continued)

*Patients with CrCl <30 mL/min were excluded from edoxaban trials; patients with CrCl <25 mL/min were excluded

from apixaban trials†Not currently approved by the US FDA for this indication.




12

Key Points

• All 3 approved TSOAs have rapid onset and

offset

• No bridging requirement*

• Important consideration for management of

bleeding, periprocedural management

• Extent of renal clearance important

differentiator

• Dosing dependent upon renal clearance, drug-

drug interactions

*Based upon the Hokusai-VTE trial and the RE-COVER trials at least 4 days of injectable anticoagulation are required

for VTE treatment.

Oral Anticoagulation use in Stroke Prevention in Atrial Fibrillation




13

TSOAs vs Adjusted-Dose Warfarin for SPAF

RE-LY1 ROCKET AF2 ARISTOTLE3 ENGAGE AF4

Drug Dabigatran Rivaroxaban Apixaban Edoxaban

# Randomized 18,113 14,264 18,201 21,105

Dose and

Frequency

150 mg BID

110 mg BID20 mg QD 5 mg BID

60 mg QD

30 mg QD

Dose

AdjustmentNo 20 mg – 15 mg 5 mg – 2.5 mg

60 mg – 30 mg

30 mg – 15 mg

Target INR 2.0 – 3.0 2.0 – 3.0 2.0 – 3.0 2.0 – 3.0

Design PROBE Double blind Double blind Double blind

PROBE, prospective, randomized, open-label, blinded end point evaluation

1. Connolly SJ et al. N Engl J Med. 2009;361:1139-1151. 2. Patel MR et al. N Engl J Med 2011;365:883-891. 3. Granger CB et al. N Engl J Med.

2011;365:981-992. 4. Giugliano RP et al. N Engl J Med. 2013;369:2093-2104.

Overview of Phase 3 Trials

TSOAs vs Adjusted-Dose Warfarin for SPAF

HR, hazard ratio

1. Connolly SJ et al. N Engl J Med. 2010;363:1875-1876. 2. Patel MR et al. N Engl J Med 2011;365:883-891. 3. Granger CB et al. N Engl J Med.

2011;365:981-992. 4. Giugliano RP et al. N Engl J Med. 2013;369:2093-2104.

0.5 21

Dabigatran 150 mg BID1

Rivaroxaban 20 mg QDay2*

Apixaban 5 mg BID3

Favors TSOA

Favors Warfarin

HR=0.79

HR=0.66

HR=0.88

Edoxaban 60 mg QDay4 HR=0.79


All S

tro

ke o

r S

E

0.5 21


Rivaroxaban 20 mg QDay2

Apixaban 5 mg BID3

Favors TSOA Favors Warfarin

HR=0.92

HR=0.94

HR=0.76

Edoxaban 60 mg QDay4HR=1.00


Isch

em

ic S

troke

0.1 21



Apixaban 5 mg BID3

HR=0.26

HR=0.51

HR=0.59



Favors TSOA Favors WarfarinHem

orr

hag

ic S

tro

ke



Apixaban 5 mg BID3

0.5 21Favors TSOA Favors Warfarin

HR=0.93

HR=1.04

HR=0.69



0.0

Majo

r Ble

ed

ing

Favors Warfarin

All TSOAs as effective as adjusted-dose warfarin to decrease stroke or systemic

embolism with lower risk for hemorrhagic stroke




14

TSOAs vs Adjusted-Dose Warfarin for SPAF (continued)

Outcome

(RR ±95% CI)

RE-LY1,2

(dabigatran

150 mg BID)

ROCKET-AF3

(rivaroxaban

20 mg QDay)

ARISTOTLE4

(apixaban

5 mg BID)

ENGAGE-AF5

(edoxaban

60 mg QDay)

Stroke/SE 0.65 (0.52-0.81) 0.88 (0.75-1.03) 0.79 (0.66-0.95) 0.79 (0.63-0.99)

Ischemic stroke 0.76 (0.59-0.97) 0.94 (0.75-1.17) 0.92 (0.74-1.13) 1.00 (0.83-1.19)

Hemorrhagic

stroke0.26 (0.14-0.49) 0.59 (0.37-0.93) 0.51 (0.35-0.75) 0.54 (0.38-0.77)

Major bleeding 0.94 (0.82-1.08) 1.04 (0.90-1.20) 0.69 (0.60-0.80) 0.80 (0.71-0.91)

ICH 0.40 (0.27-0.60) 0.67 (0.47-0.93) 0.42 (0.30-0.58) 0.47 (0.34 -0.63)

GI 1.50 (1.19–1.89) 1.39 (1.19–1.61) 0.89 (0.70–1.15) 1.23 (1.02–1.50)

CV mortality 0.85 (0.72-0.99) 0.89 (0.73-1.10) 0.89 (0.76-1.04) 0.86 (0.77-0.97)

All-cause

mortality0.88 (0.77-1.00) 0.85 (0.70-1.02) 0.89 (0.80-0.99) 0.92 (0.83-1.01)

1. Connolly SJ et al. N Engl J Med. 2009;363:1139-1151. 2. Connolly SJ t al. N Engl J Med. 2014;371:1464-1465. 3. Patel MR et al. N Engl J Med

2011;365:883-891. 4. Granger CB et al. N Engl J Med. 2011;365:981-992. 5. Giugliano RP et al. N Engl J Med. 2013;369:2093-2104.

Black text indicates noninferior findings

CV, cardiovascular; ICH, intracranial hemorrhage; SE, systemic embolism

SUPERIOR INFERIOR NONINFERIOR

Selecting Among Available TSOAs

Savelieva I et al. Clin Cardiol. 2013 Nov 19. [Epub ahead of print].

ACS, acute coronary syndromes; CAD, coronary artery disease

Match Specific Patient Characteristics to a TSOA with a Complementary Profile

IF the patient has… THEN consider a TSOA with…

High bleeding risk (HAS-BLED >3) Lowest bleeding risk

Previous GI bleed or high risk Lowest reported incidence of GI bleed

High risk of ischemic stroke with

low bleeding riskLowest risk for ischemic stroke

Previous stroke (secondary prevention)Evidence of greatest reduction of

secondary stroke

CAD, previous MI, or high risk for ACS/MI Positive effect in ACS

Renal impairment Less dependence on renal function

GI upset/disorders No reported GI side effects

A preference for convenient dosing Once-daily dosing




15

Key Points

• All TSOAs • Equivalent to standard warfarin based on primary outcome of

stroke or systemic embolic event

• Decreased risk for ICH, lower rates of other types of bleeding

• Strategies for selection among TSOAs based on PK/PD, comorbidities, patient preferences

Clinical pharmacists can take

an active role in selection of

the most appropriate TSOA for

individual patients, provide

patient education, and provide

ongoing management.

Oral Anticoagulation use in Deep Vein Thrombosis and Pulmonary Embolism

John Fanikos, RPh, MBA




16

Design of TSOA VTE Trials: Acute and Chronic

Initiation

Extended

Treatment

Extended

Treatment

Initiation and Early Maintenance

Early Maintenance

DVT/PE

1. Fontana P et al. Eur Heart J. 2014;35:1836-1843. 2. Dobesh PP et al. Drugs. 2014;74:2015-2032. By permission of Oxford University Press.

A

Dabigatran

Edoxaban

B

Apixaban

Rivaroxaban

RE-COVER, RE-COVER II, HOKUSAI

EINSTEIN-DVT, EINSTEIN-PE, AMPLIFY

RE-MEDY,

RESONATE

EINSTEIN-EXT

AMPLIFY-EXT

Study DrugDuration,

mo# Pts

PE or

PE & DVT,

n (%)

Isolated

DVT,

n (%)

Unprovoked,

n (%)

Previous

VTE,

n (%)

TTR on

VKA,

%

RE-COVER

Dabigatran6 2539 786 (31) 1749 (69) Not reported 649 (26) 60

RE-COVER II

Dabigatran6 2568

815–819

(32)

1748-

1750 (68)Not reported (17.5) 57

EINSTEIN-

DVT

Rivaroxaban

3/6/12* 3449 23 (1) 3405 (99) 2138 (62) 666 (19) 58

EINSTEIN-PE

Rivaroxaban3/6/12* 4832 4832 (100) 0 (0) 3117 (65) 944 (20) 63

AMPLIFY

Apixaban6 5395 1836 (34) 3532 (65) 4845 (90) 872 (16) 61

HOKUSAI

Edoxaban3/6/12* 8240 3319 (40) 4921 (60) 5410 (66)

1520

(18)64

Efficacy/Safety for Treatment of Acute Symptomatic VTE: A Meta-Analysis

*Treatment duration defined by treating physician

TTR, time in therapeutic range; VKA, vitamin K antagonist1. van der Hulle T et al. J Thromb Haemost. 2014;12:320-328. 2. Dobesh PP et al. Drugs. 2014;74:2015-2032. © 2014 John Wiley and Sons.

Used with permission.




17

OutcomePooled Absolute Risk

Difference, % (95% CI)

NNT with TSOAs to Prevent

One Event (95% CI)

Recurrent VTE -0.24 (-0.60–0.11) 417 (167–909)

Fatal PE 0.01 (-0.06–0.08) 10 000 (1667–1250)

Overall Mortality -0.10 (-0.47–0.28) 1000 (213–357)

Major Bleeding -0.67 (-1.13 to -0.21) 149 (88–476)

Non-fatal Bleeding at a

Critical Site-0.38 (-0.65 to -0.10) 263 (153–1000)

CRNM Bleeding -1.77 (- 0.340 to -0.15) 56 (29–667)

Non-Fatal ICH -0.14 (-0.31–0.03) 714 (323–3333)

Major GI Bleeding -0.16 (-0.42–0.11) 625 (238–909)

Fatal Bleeding -0.09 (-0.17–0.00) 1111 (588–0)

Efficacy/Safety for Treatment of Acute Symptomatic VTE: A Meta-Analysis (continued)

van der Hulle T et al. J Thromb Haemost. 2014;12:320-328. © 2014 John Wiley and Sons. Used with permission.

TSOAs decrease the risk for recurrent VTE and major bleeding compared to VKAs

Extended Treatment Trials for VTE Prevention

Study# Pts

Duration

Drug and

Treatment

Duration

Recurrent

VTE, %,

TSOA vs

Comparator

Major

Hemorrhage

No. Fatal

Major Bleeds

(Case Fatality

rate, %)

AMPLIFY-

Extension1*

2482

1 y

Apixaban 5 mg BID

Apixaban 2.5 mg BID

Placebo

1.7

1.7

8.8

0.1

0.2

0.5

0

0

0

EINSTEIN-

Extension2a

1196

6 or 12

mo

Rivaroxaban 20 mg

QD

Placebo

1.3

7.1

0.7

0

0

0

RE-SONATE3†1343

≥6 mo

Dabigatran 150 mg

BID

Placebo

0.4

5.6

0.3

0

0

0

RE-MEDY3†2856

6-36 mo

Dabigatran 150 mg

BID

Warfarin (INR 2-3)

1.8

1.3

0.9

1.8

0

1(4)

1. Agnelli G et al; AMPLIFY-EXT Investigators. N Engl J Med. 2013; 368:699-708. 2. The EINSTEIN-DVT Investigators. N Engl J Med.

2010;363:2499-2510. 3. Schulman S et al; RE-MEDY and RE-SONATE Trial Investigators. N Engl J Med. 2013; 368:709-718.

*Patients had undergone 6 to 12 mo of anticoagulation prior to study entry †Patients had undergone ≥3 mo of anticoagulation therapy prior to study entry

TSOAs decrease the risk for recurrent VTE vs placebo or VKA with a low risk of major hemorrhage




18

TSOA Selection for VTE Prevention and Treatment

Co-morbidity or Characteristic Agent Rationale

Initial parenteral therapyDabigatran, rivaroxaban,

apixaban, edoxaban

Allowance of 48-72 h initial

treatment before randomization

Renal dysfunction (CrCl ≥ 25 mL/min to

≤ 30 mL/min)Apixaban Trial exclusion criteria

Low body weight, < 60 kg Edoxaban Trial dosing adjustment

Cancers and thrombophilia None Limited trial data

AffordabilityNone, aspirin, or

preference Similar costs

Concurrent clopidogrel Rivaroxaban Concomitant use allowed

Chronic NSAID use Apixaban Concomitant use allowed

PE with elevated biomarkers Edoxaban High-risk trial sub-populations

Compliance challenges Rivaroxaban, edoxaban Once daily dosing

Prior myocardial infarctionRivaroxaban, apixaban,

edoxaban

MI events associated with

dabigatran

Propensity for bleeding Rivaroxaban, apixaban Clinical reductions in major bleeding

Multiple meds (drug interactions) Edoxaban, apixaban Allow for dose reduction

Dobesh PP et al. Drugs. 2014;74:2015-2032.

Key Points

• Pharmacists play an important role in preventing and managing VTE

• Work with other clinicians to ensure patients receive therapies demonstrated to provide best outcomes

• Provide patient education:

• Risks for thromboembolism and bleeding and what to do in

case these events occur

• Oral and injectable anticoagulant therapy and how to

maximize outcomes with these agents




19

Addressing Clinical Challenges: Focus on Coagulation Monitoring and Management of Bleeding

Periprocedural Management of Patients on OACs

• ~250,000 pts/y in North America1,2

• ~1 in 10 pts on chronic VKAs2

• Successful use of OAC therapy in this setting requires a balance that minimizes risk for TE, risk for bleeding3

• Clinical pharmacy interventions include4:• Proper anticoagulant selection, dosage before, during,

after procedure• Pre-procedure timing of discontinuation • Careful monitoring for early bleeding signs, symptoms

• Laboratory monitoring when applicable

• Determining when to reinitiate

1. Spyropoulos AC et al. Blood. 2012;120:2954-2962. 2. Douketis JD et al. Chest. 2008;133 6 Suppl:299S-339S. 3. Nutescu EA. Am J Health-Syst Pharm.

2013;70(Suppl 1):S3-S11. 4. Dager WE. Am J Health-Syst Pharm. 2013; 70 (Suppl 1):S21-S31.




20

Managing TSOAs Before Surgery or Invasive Procedures

1. Nutescu EA. Am J Health-Syst Pharm. 2013;70(Suppl 1):S3-S11. 2. Schulman S et al. Blood. 2012;119:3016-3023. 3. Pradaxa (dabigatran etexilate

mesylate) [prescribing information]. Ridgefield, CT: Boehringer Ingelheim Pharmaceuticals Inc.; 03/2014.

Calculated CrCl, mL/min

Half-life1

Timing of Last Dose Before Surgery2,3

Standard Risk of Bleeding*

High Risk of Bleeding†

Dabigatran

≥80 11–22 h 24 h

2 d(PI: Consider longer times if major surgery, spinal puncture, spinal or epidural catheter, patients in whom complete hemostasis may

be required

50-79 12–34 h24 h

(PI: Discontinue 1-2 d before if CrCl ≥50 mL/min)

2 d

30-49 13–23 h2 d

(PI: Discontinue 3-5 d before if CrCl <50 mL/min)

4 d

<30 22–35 h 4 d 6 d

*Examples: cardiac catheterization, ablation therapy, colonoscopy without removal of large polyps, uncomplicated

laparoscopic procedures†Examples: major cardiac/cancer/urologic/vascular surgery, insertion of pacemakers/defibrillators, neurosurgery,

large hernia surgery

PI, prescribing information

Managing TSOAs Before Surgery or Invasive Procedures (continued)

Calculated CrCl, mL/min Half-life, hTiming of Last Dose Before Surgery1-4

Standard Risk of Bleeding* High Risk of Bleeding†

Rivaroxaban PI: Discontinue ≥24 h before PI: Discontinue ≥24 h before

≥80 8 24 h 2 d

50-79 9 24 h 2 d

30-49 9 1–2 d 3–4 d

<30 10 2 d 4 d

Apixaban PI: Discontinue ≥24 h before PI: Discontinue ≥48 h before

≥80 15 24 h 2 d

50-79 15 24 h 2 d

30-49 18 1–2 d 3–4 d

<30 17 2 d 4 d

Edoxaban

>80 (other data not available) 9–11 N/A N/A

1. Nutescu EA. Am J Health-Syst Pharm. 2013;70(Suppl 1):S3-11. 2. Schulman S et al. Blood. 2012;119:3016-3023. 3. Xarelto (rivaroxaban) [prescribing information]. Titusville, NJ: Janssen Pharmaceuticals, Inc.; 3/2014. 4. Eliquis (apixaban) [prescribing information]. Princeton, NJ: Bristol-Myers Squibb Company; 8/2014.

*Examples: cardiac catheterization, ablation therapy, colonoscopy without removal of large polyps, uncomplicated

laparoscopic procedures†Examples: major cardiac/cancer/urologic/vascular surgery, insertion of pacemakers/defibrillators, neurosurgery,

large hernia surgery




21

Resuming TSOAs After Procedures or Surgery • Depends solely on postoperative risk for bleeding1,2

• Risk for major bleeding clearly outweighs risk for TE1

• Major abdominal, urologic surgery: Delay TSOAs until no drainage or signs of active bleeding

• Procedures with good hemostasis shortly afterward: Resume TSOAs a minimum of 4–6 h postsurgery

• Bowel paralysis, bridging with a parenteral anticoagulant may be required

• Dabigatran, rivaroxaban, apixaban: Generally resume 24–48 h

after minor procedure; 48–72 h after major surgery if

hemostasis achieved2

• Dabigatran: Resume with half-dose (75 mg) for 1st dose, then

usual maintenance dose1

• Rivaroxaban: Resume with 10 mg, then usual maintenance

dose1

TE, thromboembolism

1. Schulman S et al. Blood. 2012;119:3016-3023. 2. Nutescu EA. Am J Health-Syst Pharm. 2013;70(Suppl 1)S2-S11.

Managing Bleeding Events:Timing of Last Dose and Renal Function

Property Dabigatran1,2 Rivaroxaban1,3 Apixaban1,4 Edoxaban5

Renal clearance of

absorbed dose, %80 36 27 35

Half-life in renal impairment, h

CrCl ≥80 mL/min 11–22 8 15

10–14CrCl 50-79 mL/min 12–34 9 15

CrCl 30-49 mL/min 13–23 9 18

CrCl <30 mL/min 22–35 10 17

“Dialyzable”

Yes

49%–57%

cleared from

plasma*

Not expected

Unlikely

(14% decrease

in exposure)

Minimal effect

1.Nutescu EA. Am J Health-Syst Pharm. 2013;70(Suppl 1):S3-11. 2. Pradaxa® (dabigatran etexilate mesylate) [prescribing information]. Ridgefield, CT:

Boehringer Ingelheim Pharmaceuticals Inc.; 9/2014. 3. Xarelto® (rivaroxaban) [prescribing information]. Titusville, NJ: Janssen Pharmaceuticals, Inc.;

9/2014. 4. Eliquis® (apixaban) [prescribing information]. Princeton, NJ: Bristol-Myers Squibb Company; 8/2014.

*High-flux dialyzer, blood flow rate 200 mL/min, dialysate flow rate 700 mL/min, ~49% of total dabigatran cleared

from plasma over 4 hours and 57% with blood flow rate 300 mL/min




22

Managing Bleeding Events:Risk Stratification• Minor bleeding (eg, epistaxis, ecchymosis, menorrhagia)

• Withdraw TSOA for ≥1 d; provide definitive interventions

• Restart TSOA at lower dose for short period

• Moderate bleeding (eg, upper or lower GI bleeding) • Stop anticoagulant and monitor carefully

• Consider activated charcoal* if bleeding detected w/in 2 h of TSOA ingestion

• Identify and definitively treat bleeding source

• Consider extended TSOA withdrawal • Consider low dose parenteral anticoagulant for patients at high risk of

thrombosis to allow healing

• Provide transfusion therapy (RBCs) for symptomatic anemia

• Ensure renal function stable*Dabigatran and apixaban absorption will be reduced by administration of activated charcoal; the use of activated

charcoal to reduce absorption in case of rivaroxaban overdose may be considered

GI, gastrointestinal; RBC, red blood cells

Schulman S et al. Blood. 2012;119:3016-3023.

Managing Bleeding Events:Risk Stratification (continued)

• Immediate withdrawal of anticoagulant, antiplatelet drugs

• Verify timing of last dose

• Consider activated charcoal* if bleeding detected within 2 h of TSOA ingestion1-6

• Consider offset of anticoagulant effect and renal function

• Aggressive clinical monitoring

• Transfuse packed RBCs in response to proven/anticipated severe anemia

• Consider 4-factor PCC

• Prior to administration of PCC or rVIIa, document TSOA effect and do not treat if normal values

• PT for direct factor Xa inhibitors

• aPTT for dabigatran

• Aggressively identify and treat bleeding source

• Supportive therapies

• Inotropes, ventilation, and ICU admission as needed

aPTT, activated partial thromboplastin time; ICU, intensive care unit; PCC, prothrombin complex concentrate; rVIIa,

recombinant factor VIIa

*Dabigatran and apixaban absorption will be reduced by administration of activated charcoal; the use of activated

charcoal to reduce absorption in case of rivaroxaban overdose may be considered

1. Schulman S et al. Blood. 2012;119:3016-3023. 2. Weitz JI et al. Circulation. 2012:126;2428-2432. 3. Nutescu EA. Am J Health-Syst Pharm.

2013;70(Suppl 1):S3-11. 4. Pradaxa [package insert]. Ridgefield, CT: Boehringer Ingelheim Pharmaceuticals Inc.; 9/2014. 5. Xarelto [package insert.

Titusville, NJ: Janssen Pharmaceuticals, Inc.; 9/2014. 6. Eliquis [package insert]. Princeton, NJ: Bristol-Myers Squibb Company; 8/2014.

Major and life-threatening bleeding1,2




23

Recommended Dosing of Concentrated Clotting Factor Products*

Repletion

Agent

Clotting

Factors

Replaced1,2

Dose(s) for Repletion of Specific OAC†

Warfarin1 Dabigatran1 Rivaroxaban1/Apixaban2¶

PCC3II, IX and X

(inactivated)25-50 units/kg … 50 units/kg

PCC4II, VII, IX and X

(inactivated)25-50 units/kg 25-50 units/kg 25-50 units/kg

aPCC

II, IX, X

(inactivated)

and VII

activated -

FEIBA)

500 units for INR <5 and

1000 units for INR ≥5

Up to 25 units/kg

initially with

subsequent doses

based on response1

FEIBA: 50 IE /kg up

to a max of 200

IE/kg/day3

Up to 25 units/kg initially;

no data available in

patients with active

bleeding; 80 units/kg1

FEIBA: 50 IE /kg up to a

max of 200 IE/kg/day3

rFVIIa VII (activated) 17.7-53.4 μg/kg 20-120 μg/kg 20-120 μg/kg

*None of the PCCs are indicated for the urgent reversal of anticoagulation. †Experience with doses listed in this table is limited; consult

current references and product label for most current information. ¶Limited data are available for apixaban reversal; however, it may be

rational to apply information from rivaroxaban b/c of their similar mechanisms of action.

FFP, fresh frozen plasma; PCC3, 3-factor PCC; PCC4, 4-factor PCC

1. Nutescu EA et al. Am J Health Syst Pharm. 2013;70:1914-1929. ©2013, American Society of Health-System Pharmacists, Inc. All rights reserved.

Reprinted with permission. 2. Babilonia K et al. Thromb J. 2014; Apr 17;12:8. doi: 10.1186/1477-9560-12-8. eCollection 2014. 3. Heidbuchel H et al.

Europace. 2013;15:625-651.

4-Factor PCC: Individualize Dosing

Pre-treatment INR 2–<4 4–6 >6

Dose* (units of Factor

IX)/kg body weight 25 35 50

Maximum dose† (units of

Factor IX)

Not to exceed

2500

Not to exceed

3500

Not to

exceed 5000

Dosing is based on body weight. Dose based on actual potency as stated on the carton, which will vary

from 20-31 Factor IX units/mL after reconstitution. Nominal potency is 500 or 1000 units per vial,

approximately 25 units per mL after reconstitution.

*Units refer to international units†Dose is based on body weight ≤100 kg. For patients weighing >100 kg, maximum dose should not be exceeded.

KCentra (Prothrombin Complex Concentrate [Human]) [prescribing information]. Kankakee, IL: CSL Behring LLC; Dec. 2013.




24

TSOAs: Antidotes in Development1

Target Mechanism of ActionInvestigation

Status

Idarucizumab Dabigatran

Humanized Fab: specifically binds dabigatran

(binding affinity ~350 x higher than binding of dabigatran to thrombin)

Bleeding patients and surgical

patients2

Andexanet alfa (PRT064445)

FXa inhibitors

Recombinanthuman FXa variant: competitive affinity for direct FXa inhibitors

Healthy volunteers3,4

Aripazine (PER977)

UniversalSynthetic small molecule:

charge-charge interactions (heparin); hydrogen bonds (TSOAs)5

Phase I6

1. Lauw M et al. Can J Cardiol. 2014; doi: 10.1016/j.cjca.2014.01.015; 2. Clinicaltrials.gov: NCT02104947. 3. Clinicaltrials.gov: NCT02220725. 4. Clinicaltrials.gov: NCT02207725. 5. Bakhru S et al. AHA 2013; abstr 11395. 6. Perosphere. Latest News:Perosphere and Daiichi Sankyo Enter into a Clinical Trial Agreement to Evaluate the Efficacy and Safety of PER977 to Reverse the Anticoagulant Activity of the Investigational, Oral, Once-Daily Factor XA Inhibitor Edoxaban. www.perosphere.com/content/news/httpwww.perosphere.comcontentnewsreleases042513.htm. Accessed 11/17/14.

Clinical Pharmacy Call to Action: Ensuring Appropriate Anticoagulation

Sarah Spinler, PharmD, FCCP, FCPP, FAHA, FASHP, AACC,BCPS–AQ Cardiology




25

Clinical Pharmacy Call to Action:ASHP Statement 2012

Pharmacist’s Leadership Role in Anticoagulation

Therapy Management

• Advocate for role in development, implementation,

monitoring, and assurance of continuity of care

• Coordinate individualized care within anticoagulation

management programs

• Encourage pharmacist programs to educate stakeholders on

anticoagulant medication use, drug interactions, adverse

events, importance of adherence, and monitoring

ASHP. Medication Therapy and Patient Care: Organization and Delivery of Services–Positions.

www.ashp.org/DocLibrary/BestPractices/OrganizationPositions.aspx. Accessed 11/12/14.

ASHP Anticoagulation Resource Center

“Anticoagulation is high risk therapy involving complex dosing, monitoring, and ensuring patient adherence with outpatient therapy. Regulations have demonstrated the need for pharmacist involvement with anticoagulation patient management.”

http://www.ashp.org/anticoagulation

American Society of Health-System Pharmacists. Anticoagulation Resource Center. www.ashp.org/anticoagulation. Accessed 11/14/14.




26

The Anticoagulation Forum

• Mission

• To offer insight and expertise to those of you on the front lines

• Goals

• To have a community where physicians, pharmacists, and nurses can come to find the latest research, engage in educational programs, and find tools to evaluate and enhance their practice

• Ultimate goal, to provide a resource where practice changing, evidence-based information is readily available

• Anticoagulation Forum Centers of Excellence Resources

• Quality improvement organizations dedicated to reducing anticoagulation adverse events – eg, The New York Anticoagulation Coalition

http://acforum.org/

The Anticoagulation Forum. http://acforum.org/#&panel1-2. Accessed 11/14/14.

Take-Home Points

• Take an active role in anticoagulation management

• Remember how to use anticoagulants

• Consider trial design, drug-drug, drug-food interactions when selecting a TSOA

• Understand strategies for the management of bleeding events

• Keep up with current product labeling and data

Remember, you are the medication experts!




27

Interactive Case Review and Panel Discussion

JB, 71-Year-Old White Female With NVAF

• Presents to cardiologist for annual follow-up

• Past medical history• NVAF x 4 years• Hypertension x 18 years• Osteoarthritis

• Lives alone but still drives and is active volunteering in the community

• Medications• Warfarin 2.5 mg alternating with 5 mg every other day• Hydrochlorothiazide 50 mg po q day• Diltiazem XR 120 mg po BID• Dofetilide 500 mcg po BID• Calcium and vitamin D po BID• Multivitamin po q day• Ibuprofen 400 mg po tid prn pain

• INR variable, ranging from 1.4 to >3 on 2 occasions in last 6 mo

• Current labs:• Renal function normal• INR: 2.8




28

Panel Discussion• What are the risks/benefits of continuing warfarin?

• What are JB’s modifiable risk factors for bleeding? Falling?

• Which TSOA would you choose for this patient? Why?

• What is the appropriate dose of the selected agent for JB?



• 9 mos later JB presents to ED (driven by daughter) fainting and falling at home

• Patient in AF, no acute distress, but significant bleeding from a deep forehead laceration

• Vital signs:

• T: 98.9°F

• P: irregular, 92

• BP: 132/76 mm Hg

• RR: 18/min

• Pertinent laboratory values

• Hg: 14.4 g/dL

• SCr: 1.1 mg/dL (est CrCl = 63 ml/min)

• INR: 1.6

• Her daughter says JB’s last dose of TSOA was about 4 hours ago

ED, emergency department




29

Panel Discussion

• What is JB’s CHA2DS2-VASc score?

• HAS-BLED = 3

• How would you manage this bleeding episode?

• What are JB’s modifiable risk factors for bleeding? Falling?

• Would you continue treatment with a TSOA in this patient?


1. Lahaye S et al. Thromb Haemost. 2014;111(3):465-473; online Suppl 2: 111.4. 2. Lip GYH, et al. Chest. 2010; 137: 263-272.Reproduced with

permission from the American College of Chest Physicians.

1,2


• JB presents for follow-up visit at the outpatient anticoagulation clinic 3 mo later

• Taking dabigatran 150 mg PO BID

• Denies problems and any bleeding events

• Reports adherence to dabigatran; this is confirmed by Rx refill history

• Note that she is having a cardiac ablation in 2 weeks, wants to know if she should keep taking her dabigatran




30

GJ, 52-Year-Old Woman With Post-op Calf Pain

Medical History

• Longstanding hypertension

Clinical Course

• Extensive L medial meniscus injury requiring arthroscopic surgical repair

• Postop day #3: New L calf discomfort and presented to ED at 04:00 AM Monday complaining of severe L calf pain

• Ultrasound performed at 8:00 AM Monday morning; isolated L calf vein thrombosis was detected

• Pertinent laboratory values

• SCr: 0.9 mg/dL

• BUN: 12 mg/dL

Clinical Course (continued)

• Two days later GJ collapsed at work, transported to ED via ambulance

• ECG showed new onset AF with a rapid ventricular response of 130/m

• BP: 94/62 mm Hg

• T: 97.8°F

• Arterial oxyhemoglobin saturation: 88%

• Massive PE confirmed on chest CT scan

• Unfractionated heparin 10,000 U IV bolus, then continuous infusion of 1250 units/h

• Follow-up ECG showed reversion from AF to sinus tachycardia, at 115/m

• Heparin infusion rate decreased by 50%

• Catheter-directed thrombolysis performed successfully cardiac cath lab

• No bleeding complications


ECG, electrocardiograph; CT, computed tomography; TPA, tissue plasminogen activator




31

Panel Discussion• How would you transition treatment with a goal of

hospital discharge on day 3?

• How long should oral anticoagulation be continued?

• What ongoing monitoring is important in this case?


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