Download Controlling the Clots: Current Challenges and Emerging

Controlling the Clots: Current Challenges and
Emerging Champions in Anticoagulation
Pharmacy Practice Update Seminar Series
Monday, October 1, 2012
This activity was developed by the American Pharmacists Association and supported by
an independent educational grant from Janssen Scientific Affairs, LLC.
Controlling the Clots: Current Challenges and Emerging
Champions in Anticoagulation
Activity Description
Caring for patients on anticoagulation therapy is challenging because there is a delicate balance of
maintaining appropriate levels of anticoagulation while minimizing the potential risks associated with
therapy. In addition, health care providers must stay up to date as new information emerges that affects
how they care for their patients. During this activity, the speaker will present patient cases and lead an
engaging discussion about how to interpret emerging information to make appropriate clinical decisions
regarding anticoagulation therapy.
Learning Objectives
At the completion of this application-based activity, participants will be able to:
1. Identify current challenges in clinical practice related to anticoagulation therapy.
2. Explain the mechanism of action of warfarin, direct Factor Xa inhibitors and direct Factor IIa
inhibitor drug therapies.
3. Describe the management and recommendations/suggestions of selected situations requiring
antithrombotic therapy, including atrial fibrillation, deep venous thrombosis and pulmonary
embolism.
4. Evaluate patient cases that address current challenges in clinical practice and selected situations
and provide treatment recommendations based upon current evidence and emerging information.
5. Develop an individualized patient care plan which should include a patient specific dosing
regimen, monitoring parameters, and treatment goals.
Learning Level: Level 3
Target Audience: Pharmacists
Initial Release Date: October 1, 2012
Fee: There is no fee to participate in this activity.
Speaker
James B. Groce III, PharmD, CACP
Professor, Campbell University College of Pharmacy and Health Sciences
Clinical Assistant Professor of Medicine, University of North Carolina School of Medicine
Clinical Pharmacy Specialist–Anticoagulation, Moses Cone Health System, Greensboro, North Carolina
Speaker’s Biography
James B. Groce III, PharmD, CACP, is a Professor at the Campbell University College of Pharmacy and
Health Sciences in Buies Creek, North Carolina; a Clinical Assistant Professor of Medicine at the
University of North Carolina School of Medicine in Chapel Hill; and a Clinical Pharmacy Specialist–
Anticoagulation at Moses Cone Health System in Greensboro, North Carolina.
Dr. Groce manages an anticoagulation clinic serving more than 150 patients; he also supervises training
in anticoagulation management for Pharmacy Practice and Medicine residents at this site. Dr. Groce is
certified by the National Certification Board for Anticoagulation Providers and is a sitting member of the
Certification Board of Directors/Examiners. He has served on The Joint Commission (TJC)/National
Quality Forum (NQF) Technical Advisory Panel for creation of core measures for prevention and
treatment of venous thromboembolism, which were endorsed by TJC/NQF as standards for quality of
hospital care in 2008. Dr. Groce has been named Preceptor of the Year by the Campbell University
College of Pharmacy and Health Sciences graduating classes of 2006 and 2007. He has presented
© 2012 by the American Pharmacists Association. All rights reserved. Printed in the U.S.A.
extensively regarding the interchange of narrow therapeutic index drugs and their impact on efficacy,
safety, and pharmacoeconomics; he gave testimony before the North Carolina Legislature that resulted in
Senate Bill 945—The Prescription Refill Safety Act.
Dr. Groce has been published and cited in peer-reviewed medical and pharmacy journals as well as
pharmacy textbooks. Among his extensive research activities, Dr. Groce was one of 20 principal
investigators for a national cohort study on bridging patients, who required interruption of their chronic
anticoagulant therapy, onto low-molecular-weight-heparins (LMWH). He served as principal investigator
for a pharmacoeconomic evaluation of LMWH for outpatient therapy of deep vein thrombosis (DVT) in a
community teaching hospital setting. He also served as principal investigator at Cone Health for the DVT
FREE national registry trial and was part of the 11-member steering committee for this initiative. He has
conducted clinical evaluations of various heparin weight-based-dosing nomograms and the utility of
heparin level determinations and outcomes analysis.
Disclosures
James B. Groce III, PharmD, CACP, declares he has received fees for non-CME services directly from
the following commercial interests or their agents: Boehringer Ingelheim Pharmaceuticals, Bristol-Myers
Squibb/Pfizer Pharmaceuticals, Janssen Pharmaceuticals, Johnson & Johnson, and The Joint
Commission.
APhA’s editorial staff declares no conflicts of interest or financial interests in any product or service
mentioned in this activity, including grants, employment, gifts, stock holdings, and honoraria. For
complete staff disclosures, please see the Education and Accreditation Information section at
www.pharmacist.com/education.
Accreditation Information
The American Pharmacists Association is accredited by the Accreditation Council for
Pharmacy Education (ACPE) as a provider of continuing pharmacy education (CPE). This
activity, Controlling the Clots: Current Challenges and Emerging Champions in
Anticoagulation, is approved for 1.5 contact hours of CPE credit (0.15 CEUs). The ACPE
Universal Activity Number assigned to this activity by the accredited provider is: 202-000-12-251-L01-P.
To obtain CPE credit for this activity, participants will be required to actively participate in the entire
activity and complete an online assessment and evaluation forms located at
www.pharmacist.com/education by Friday, October 12, 2012.
This activity was developed by the American Pharmacists Association and supported by an independent
educational grant from Janssen Scientific Affairs, LLC.
© 2012 by the American Pharmacists Association. All rights reserved. Printed in the U.S.A.
Controlling the Clots: Current
Challenges and Emerging
Champions in Anticoagulation
James B. Groce III, PharmD, CACP
Professor, Campbell University College of
Pharmacy and Health Sciences
Clinical Assistant Professor of Medicine, UNC
Clinical Pharmacy Specialist-Anticoagulation
Moses Cone Health System, Greensboro NC
Development and Support
This activity was developed by the
American Pharmacists Association
and supported by an independent
education grant from Janssen
Scientific Affairs, LLC.
2
Disclosures
• James B. Groce III, PharmD, CACP, declares he
has received fees for non-CME services directly
from the following commercial interests or their
agents: Boehringer Ingelheim Pharmaceuticals,
Bristol-Myers Squibb/Pfizer Pharmaceuticals,
Janssen Pharmaceuticals, Johnson & Johnson, and
The Joint Commission.
• APhA’s editorial staff declares no conflicts of interest
or financial interests in any product or service
mentioned in this activity, including grants,
employment, gifts, stock holdings, and honoraria.
For complete staff disclosures, please see the
Education and Accreditation Information section at
www.pharmacist.com/education.
3
© 2012 by the American Pharmacists Association. All rights reserved. Printed in the U.S.A.
Accreditation Information
The American Pharmacists Association is accredited
by the Accreditation Council for Pharmacy Education
(ACPE) as a provider of continuing pharmacy education
(CPE). This activity, Controlling the Clots: Current
Challenges and Emerging Champions in Anticoagulation, is
approved for 1.5 contact hours of CPE credit (0.15 CEUs).
The ACPE Universal Activity Number assigned to this activity
by the accredited provider is: 202-000-12-251-L01-P.
To obtain CPE credit for this activity, participants will be
required to actively participate in the entire activity and
complete an online assessment and evaluation forms
located at www.pharmacist.com/education by Friday,
October 12, 2012.
4
Learning Objectives
• At the completion of this application-based activity,
pharmacists will be able to:
– Identify current challenges in clinical practice related to
anticoagulation therapy.
– Explain the mechanism of action of warfarin, direct Factor Xa
inhibitors and direct Factor IIa inhibitor drug therapies.
– Describe the management and recommendations/suggestions
of selected situations requiring antithrombotic therapy, including
atrial fibrillation, deep venous thrombosis and pulmonary
embolism.
– Evaluate patient cases that address current challenges in
clinical practice and selected situations and provide treatment
recommendations based upon current evidence and emerging
information.
– Develop an individualized patient care plan which should
include a patient specific dosing regimen, monitoring
parameters, and treatment goals.
5
Self-Assessment Question
• A patient you see in your pharmacy reports that
“…my INR response is erratic (up and down)…”
• You observe that the patient has been refilling a
•
•
prescription for warfarin based upon an original
prescription by the prescriber—that was marked for
“1 year refill authorization”—the patient is in his
10th month of refills as authorized.
You inquire: “When was the last time you saw your
anticoagulation care provider?”—and the response
was: “I have seen them five times in 10 months…”
What are your thoughts as a pharmacist about to
dispense warfarin?
6
© 2012 by the American Pharmacists Association. All rights reserved. Printed in the U.S.A.
Learning Objectives
• At the completion of this application-based activity,
pharmacists will be able to:
– Identify current challenges in clinical practice related to
anticoagulation therapy.
– Explain the mechanism of action of warfarin, direct Factor
Xa inhibitors and direct Factor IIa inhibitor drug therapies.
– Describe the management and
recommendations/suggestions of selected situations
requiring antithrombotic therapy, including atrial fibrillation,
deep venous thrombosis and pulmonary embolism.
– Evaluate patient cases that address current challenges in
clinical practice and selected situations and provide
treatment recommendations based upon current evidence
and emerging information.
– Develop an individualized patient care plan which should
include a patient specific dosing regimen, monitoring
parameters, and treatment goals.
7
Current Challenges in Clinical Practice Related
to Anticoagulation Therapy
• Essential elements of optimal anticoagulation had not
changed for 60 years
• The successful use of (anticoagulation) depends on
•
an “essential triad,” which includes:
– Vigilant clinician
– Cooperative (well-educated) patient
– Readily available and reliable laboratory
If these factors are present, continuous use of
anticoagulation is practical...and effective; if not, the
use of the drug is dangerous
Foley WT, Wright IS. Am J Med Sci. 1949;217:136-144.
Aske JM, Cherry CB. JAMA. 1950;144:97-100.
8
Current Challenges in Clinical Practice Related
to Anticoagulation Therapy.
• Pharmacist-managed anticoagulation services are the
•
•
most widely utilized case management strategies for
patients with thrombotic disease or its prevention
First Medication Therapy Management services
– Over 40 years of AC clinics
Clinics provide coordinated clinical infrastructures for:
– Patient education
– Therapeutic monitoring
– Dose adjustment to keep warfarin within its narrow
therapeutic window
Johnson SG. J Manag Care Pharm. 2009;15(suppl):S19-S25.
9
© 2012 by the American Pharmacists Association. All rights reserved. Printed in the U.S.A.
Current Challenges in Clinical Practice Related
to Anticoagulation Therapy
10 Year
52.1%
23.8%
24.2%
2.4%
2.0-3.0
<2.0
>3.0
>5.0
Medical Care
43.7%
38.2%
18.2%
2.6%
Anticoagulation clinics improve adherence
SamsaGP. Arch Intern Med. 2000;160:967.
10
Self-Assessment Question
• What is an appropriate quality
marker for anticoagulation
management for patients
maintained on warfarin?
11
Current Challenges in Clinical Practice Related
to Anticoagulation Therapy
• Calculation of time in target range
– What is the TTR for the patient below?
2.5
2
2.3
2.1
2
INR
1.6
1.7
1.5
1
0.5
0
Jan 15, 2011 Feb 15, 2011 Mar 15, 2011 Mar 29, 2011 Apr 29, 2011
Schmitt L, Speckman J, Ansell J. J Thromb Thrombolysis. 2003;15:213-216.
12
© 2012 by the American Pharmacists Association. All rights reserved. Printed in the U.S.A.
Current Challenges in Clinical Practice Related
to Anticoagulation Therapy
• 3 Methods for Calculating TTR:
Percentage of Visits in Range
• For an individual patient, the number of visits “in
range” is divided by the number of visits
3 Patient Visits with INR in Range
60% TTR
=
5 Total Patient Visits
Schmitt L, Speckman J, Ansell J. J Thromb Thrombolysis. 2003;15:213-216.
13
Current Challenges in Clinical Practice Related
to Anticoagulation Therapy
• 3 Methods for Calculating TTR:
Cross Section of Patients in Range
• For a group of patients, a date is selected and all
patients are evaluated on the last reading prior to
that date Feb 28, 2012 is selected to assess TTR for 100 patients
• Patients are evaluated using last INR readings prior to
Feb 28, 2012
• Out of 100 patients, 71 had readings in therapeutic
range
71 Patient with INR in Range
=
100 Total Patients
71% TTR
As of February 2012
Schmitt L, Speckman J, Ansell J. J Thromb Thrombolysis. 2003;15:213-216.
14
Current Challenges in Clinical Practice Related
to Anticoagulation Therapy
• 3 Methods for Calculating TTR:
% Days in Range (Rosendaal Method)
• More complicated methodology which looks at the amount of time
INR Level
between visits to determine how long the patient might have been
within the therapeutic range
– Between measurements on May 1 and May 31, it is assumed that
the patient slowly moved from 2.5 to 3.5 over 30 days
4
3.5
3
2.5
2
1.5
1
0.5
0
– On May 15th, the patient was probably over 3.0
3.5
2.8
2.5
15 days
15 days
In range Out of range
Apr 29, 2011
May 1, 2011
Patient was in range
50% of the time
May 31, 2011
Schmitt L, Speckman J, Ansell J. J Thromb Thrombolysis. 2003;15:213-216.
15
© 2012 by the American Pharmacists Association. All rights reserved. Printed in the U.S.A.
Self-Assessment Question
• How will we develop quality and
assess quality for the new oral
anticoagulants?
16
New Oral Anticoagulants Will Impact Policies
and Processes
• Availability of new oral anticoagulants will impact the
way we think about care delivery and management for
patients with atrial fibrillation
– Clinical management including guidelines/algorithms,
patient education, monitoring, etc.
– Clinical infrastructure and staffing
– Cost management including cost-sharing, benefit
design, formulary structure, etc.
Kirsch B. Manag Care. 2011;20(2):33-36.
17
Future of Anticoagulation Clinics in the Era of
New Oral Anticoagulants
• New oral anticoagulants have many potential
•
•
advantages over warfarin, including predictable
therapeutic effect at fixed doses and limited drug–
drug interactions1
– These features may allow for routine therapy
without monitoring and associated dosage
adjustments
New oral anticoagulants present both an opportunity
and a threat to anticoagulation service providers2
Traditional anticoagulation monitoring services will
have to retool if they are to remain relevant2
1. Ansell J. Hematology. 2010;221-228.
2. Nutescu EA, et al. Pharmacotherapy. 2004;24:199S-202S.
18
© 2012 by the American Pharmacists Association. All rights reserved. Printed in the U.S.A.
Self-Assessment Question
• What is desired in an anticoagulant
that will help us as pharmacists, help
the physician—and ultimately help the
patient?
19
Characteristics of an Ideal Anticoagulant
Predictable dose
response (no need for
monitoring)
High efficacy-tosafety index
Parenteral
and oral
administration
Rapid
onset of
action
Minimal
non-anticoagulant
side effects
Antidote
Minimal
drug-drug interactions
Hirsh J, et al. Blood. 2005;105(2):453-461.
20
Learning Objectives
• At the completion of this application-based activity,
pharmacists will be able to:
– Identify current challenges in clinical practice related to
anticoagulation therapy.
– Explain the mechanism of action of warfarin, direct Factor
Xa inhibitors and direct Factor IIa inhibitor drug therapies.
– Describe the management and
recommendations/suggestions of selected situations
requiring antithrombotic therapy, including atrial fibrillation,
deep venous thrombosis and pulmonary embolism.
– Evaluate patient cases that address current challenges in
clinical practice and selected situations and provide
treatment recommendations based upon current evidence
and emerging information.
– Develop an individualized patient care plan which should
include a patient specific dosing regimen, monitoring
parameters, and treatment goals.
21
© 2012 by the American Pharmacists Association. All rights reserved. Printed in the U.S.A.
Coagulation Cascade
Vitamin K-Dependent Factors
22
Warfarin: Mechanism of Action
Anticoagulant Effect Result of Vitamin K
Inhibition
23
Vitamin K-Dependent Clotting
Factors
Vitamin K
VII
Synthesis
of
X Functional
Coagulation
II
Factors
IX
24
© 2012 by the American Pharmacists Association. All rights reserved. Printed in the U.S.A.
Warfarin Mechanism of Action
Vitamin K
Antagonism
of
Vitamin K
VII
Synthesis of
NonX Functional
Coagulation
II
Factors
IX
Warfarin
25
New Oral Anticoagulants
TF/VIIa
X
IX
VIIIa
IXa
Va
Rivaroxaban
Apixaban
Xa
II
Dabigatran
IIa
Fibrinogen
Fibrin
Adapted from Weitz J, Bates S. Thromb Haemost. 2007;5(8):1607-1609
26
Mechanism of Action of Direct Factor Xa
Inhibitors
• Factor Xa sits at the junction of the extrinsic and
intrinsic pathways
• Factor Xa catalyzes the conversion of prothrombin
to thrombin
• Each molecule of Factor Xa leads to the generation
of several hundred molecules of thrombin
• Factor Xa inhibitors act upstream of initial thrombin
generation to modulate the thrombin burst
• Factor Xa inhibitor inhibits both free and bound
Factor Xa
Turpie AG. Eur Heart J. 2008;29(2):155-165.
27
© 2012 by the American Pharmacists Association. All rights reserved. Printed in the U.S.A.
Mechanism of Action of Direct Factor IIa
(Thrombin) Inhibitor
• Specific and potent direct inhibition of thrombin
• Independent of antithrombin III
• Inhibit thrombin-mediated activation of clotting factors
(V, VIII, XIII) and platelets
• Action against free (soluble) and clot-bound thrombin
• Stable anticoagulant activity
• Unaffected by factors that neutralize heparin
• Do not induce immune-mediated thrombocytopenia
Turpie AG. Eur Heart J. 2008;29(2):155-165.
28
Newer Oral Anticoagulants
Parameter
Manufacturer
Dabigatran1
Rivaroxaban2
Apixaban3
Boehringer Ingelheim
Bayer with Ortho-McNeil
Bristol-Myers Squibb with
Pfizer
Brand Name
Approval Status
Indication
Pradaxa
Xarelto
Eliquis
Approved in U.S. 2010
Approved in U.S. 2011
Approved in the EU 2011
•Stroke prevention in
patients with AF
• Thromboembolism in adult
patients undergoing
elective hip or knee
replacement surgery
• Stroke prevention in
patients with AF
• Not approved in US
• EU indication:
Prevention of venous
thromboembolism in
adult patients
undergoing elective hip
or knee replacement
surgery
150 mg bid
10 mg qd Ortho
15 mg qd Afib (Clcr 1550mL/min)
20 mg qd Afib Clcr > 50
mL/min
5 mg bid
Direct factor IIa inhibitor
Direct factor Xa inhibitor
Direct factor Xa inhibitor
Dosage
Recommendation
Mechanism of
Action
1.
2.
3.
Dabigatran etexilate prescribing information. Boehringer Ingelheim Pharmaceuticals, Inc. March 2011.
Rivaroxaban European Union summary of product characteristics. Bayer Schering Pharma AG. May 2009.
Apixaban European Union summary of product characteristics. Pfizer and Bristol-Myers Squibb. May 2011.
29
Pharmacokinetic Properties of
the New Oral Anticoagulants
Parameter
Dabigatran
Rivaroxaban
Apixaban
T1/2
12-14 hours
5-9 hours
8-15 hours
Conjugation (esterase
catalyzed hydrolysis in
liver or plasma)
Oxidation (mainly
via CYP3A4) and
hydrolysis
70% unchanged;
30% inactive
metabolites
Renal Excretion
80%
36%
30%
Substrate for PGlycoprotein
Yes
Yes
Yes
Metabolized by
CYP3A4
No
Yes
Yes
Metabolism
Wittkowsky AK. J Thromb Thrombolysis. 2010;29:182-191.
Ufer M. Thromb Haemost. 2010;103:572-585.
30
© 2012 by the American Pharmacists Association. All rights reserved. Printed in the U.S.A.
Differences Between New Oral
Anticoagulants and Warfarin
Parameter
Oral Anticoagulants
Warfarin
Rapid
Slow
Onset/Offset of
action
Dose–anticoagulant
effect relationship
Food–drug
interactions
Monitoring for
anticoagulant effect
Linear
Predictable
Low probability
of interaction
Moderate probability of
interaction
Not required
Not available
Required POCT and
PST Available
POCT=point-of-care testing
PST=patient self-testing
Wittkowsky AK. J Thromb Thrombolysis. 2010;29:182-191.
Ufer M. Thromb Haemost. 2010;103:572-585.
31
Potential Drug Interactions With
the New Oral Anticoagulants
Parameter
Drug
Interactions
Dabigatran
•
•
•
•
•
•
•
•
•
•
•
•
Clarithromycin
Quinidine
Amiodarone
Verapamil
Rifampicin
Pantoprazole
Aspirin
Naproxen
Diclofenac
Clopidogrel
Warfarin
Heparin
Rivaroxaban
•
•
•
•
•
•
•
•
•
•
•
•
•
•
•
Ketoconazole
Itraconazole
Voriconazole
Ritonavir
Posaconazole
Clarithromycin
Rifampicin
Phenytoin
Carbamazepine
Aspirin
Naproxen
Diclofenac
Clopidogrel
Warfarin
Heparin
Walenga JM, Adiguzel C. Int J Clin Pract. 2010;64:956-967.
32
PRADAXA (dabigatran)
Drug-Drug Interaction Profile
• Concomitant use with rifampin reduces exposure to
dabigatran and should generally be avoided
• In patients with moderate renal impairment (CrCl
30–50 mL/min), consider reducing the dose of
dabigatran to 75 mg twice daily when concomitantly
administered with the P-gp inhibitor dronedarone or
systemic ketoconazole
Dabigatran etexilate prescribing information. Boehringer Ingelheim Pharmaceuticals, Inc. 2012.
33
© 2012 by the American Pharmacists Association. All rights reserved. Printed in the U.S.A.
XARELTO (rivaroxaban):
Drug-Drug Interaction Profile
Drugs (examples)
PK/PD Effects
Recommendation
Combined P-gp and strong CYP3A4 inhibitors
Ketoconazole, itraconazole,
lopinavir/ritonavir, ritonavir,
indinavir/ritonavir, conivaptan
Concomitant use increases rivaroxaban exposure and
PD effects; significant increases in rivaroxaban exposure
may increase bleeding risk
Avoid concomitant use
Combined P-gp and strong CYP3A4 inducers
Carbamazepine, phenytoin,
rifampin, St. John’s wort
Concomitant use may decrease efficacy of rivaroxaban
Avoid concomitant use if
these drugs must be
coadministered
Combined P-gp and weak or moderate CYP3A4 inhibitor in the presence of renal impairment
(CrCl 15 to 50 mL/min)
Amiodarone, diltiazem,
verapamil, quinidine,
ranolazine, dronedarone,
felodipine, erythromycin,
azithromycin, cimetidine,
chloramphenicol
Based on simulated PK data, patients with renal
impairment receiving rivaroxaban concomitantly with
combined P-gp and weak or moderate CYP3A4 inhibitors
may have significant increases in exposure compared with
patients with normal renal function. While increases in
exposure can be expected, results from ROCKET AF,
which allowed concomitant use of combined P-gp and
weak or moderate CYP3A4 inhibitors, did not show an
increase in bleeding in patients with CrCl 30 to <50 mL/min
Use only if potential
benefit justifies risk
Rivaroxaban prescribing information. Janssen Pharmaceuticals. 2011.
34
Learning Objectives
• At the completion of this application-based activity,
pharmacists will be able to:
– Identify current challenges in clinical practice related to
anticoagulation therapy.
– Explain the mechanism of action of warfarin, direct Factor
Xa inhibitors and direct Factor IIa inhibitor drug therapies.
– Describe the management and
recommendations/suggestions of selected situations
requiring antithrombotic therapy, including atrial fibrillation,
deep venous thrombosis and pulmonary embolism.
– Evaluate patient cases that address current challenges in
clinical practice and selected situations and provide
treatment recommendations based upon current evidence
and emerging information.
– Develop an individualized patient care plan which should
include a patient specific dosing regimen, monitoring
parameters, and treatment goals.
35
Atrial Fibrillation 2012 ACCP
Recommendations/Suggestions
• The CHADS2 score is has been extensively validated and is
easy for clinicians to remember and use:
Risk factor
Points
C
Recent Congestive heart failure exacerbation
1
H
Hypertension
1
A
Age ≥75 years
1
D
Diabetes mellitus
1
S
Prior history of Stroke or transient ischemic attack
2
You JJ, et al. CHEST. 2012;141;e531S-e575S.
36
© 2012 by the American Pharmacists Association. All rights reserved. Printed in the U.S.A.
Atrial Fibrillation 2012 ACCP
Recommendations/Suggestions
For patients with AF, including those with paroxysmal AF, who are at low
risk of stroke (e.g., CHADS2 score = 0), we suggest no therapy rather
than antithrombotic therapy (Grade 2B). For patients who do choose
antithrombotic therapy, we suggest aspirin (75 mg to 325 mg once daily)
rather than oral anticoagulation (Grade 2B) or combination therapy with
aspirin and clopidogrel (Grade 2B).
Remarks: Patients who place an exceptionally high value on stroke
reduction and a low value on avoiding bleeding and the burden
associated with antithrombotic therapy are likely to choose antithrombotic
therapy rather than no antithrombotic therapy.
You JJ, et al. CHEST. 2012;141;e531S-e575S.
37
Atrial Fibrillation 2012 ACCP
Recommendations/Suggestions
Other factors that may influence the choices above are a
consideration of patient-specific bleeding risk and the
presence of additional risk factors for stroke, including age
65 to 74 years and female gender, which have been more
consistently validated, and vascular disease, which has been
less well validated. The presence of multiple non-CHADS2
risk factors for stroke may favor oral anticoagulation therapy.
You JJ, et al. CHEST. 2012;141;e531S-e575S.
38
Atrial Fibrillation 2012 ACCP
Recommendations/Suggestions
For patients with AF, including those with paroxysmal AF, who are at
intermediate risk of stroke (e.g., CHADS2 score = 1), we recommend oral
anticoagulation rather than no therapy (Grade 1B). We suggest oral
anticoagulation rather than aspirin (75 mg to 325 mg once daily) (Grade
2B) or combination therapy with aspirin and clopidogrel (Grade 2B). For
patients who are unsuitable for or choose not to take an oral
anticoagulant (for reasons other than concerns about major bleeding), we
suggest combination therapy with aspirin and clopidogrel rather than
aspirin (75 mg to 325 mg once daily) (Grade 2B).
Remarks: Patients who place an exceptionally high value on stroke
reduction and a low value on avoiding bleeding and the burden
associated with anticoagulant therapy are likely to choose oral
anticoagulation rather than antiplatelet therapy.
You JJ, et al. CHEST. 2012;141;e531S-e575S.
39
© 2012 by the American Pharmacists Association. All rights reserved. Printed in the U.S.A.
Atrial Fibrillation 2012 ACCP
Recommendations/Suggestions
Other factors that may influence the choice among
antithrombotic therapies are a consideration of bleeding risk
and the presence of additional risk factors for stroke,
including age 65 to 74 years and female gender, which have
been more consistently validated, and vascular disease,
which has been less well validated. The presence of multiple
additional non-CHADS2 risk factors for stroke may favor oral
anticoagulation therapy.
You JJ, et al. CHEST. 2012;141;e531S-e575S.
40
Atrial Fibrillation 2012 ACCP
Recommendations/Suggestions
For patients with AF, including those with paroxysmal AF,
who are at high risk of stroke (e.g., CHADS2 score = 2), we
recommend oral anticoagulation rather than no therapy
(Grade 1A), aspirin (75 mg to 325 mg once daily) (Grade
1B), or combination therapy with aspirin and clopidogrel
(Grade 1B). For patients who are unsuitable for or choose
not to take an oral anticoagulant (for reasons other than
concerns about major bleeding), we recommend combination
therapy with aspirin and clopidogrel rather than aspirin (75
mg to 325 mg once daily) (Grade 1B).
You JJ, et al. CHEST. 2012;141;e531S-e575S.
41
Atrial Fibrillation 2012 ACCP
Recommendations/Suggestions
For patients with AF, including those with paroxysmal AF, for
recommendations in favor of oral anticoagulation (excluding
recommendations for patients with mitral stenosis, stable
coronary artery disease, intracoronary stents, and acute
coronary syndrome), we suggest dabigatran 150 mg twice
daily rather than adjusted-dose vitamin K antagonist (VKA)
therapy (target INR range, 2.0-3.0) (Grade 2B).
You JJ, et al. CHEST. 2012;141;e531S-e575S.
42
© 2012 by the American Pharmacists Association. All rights reserved. Printed in the U.S.A.
VTE Treatment 2012 ACCP
Recommendations/Suggestions
• In patients with acute DVT of the leg, we recommend
early initiation of VKA (e.g., same day as parenteral
therapy is started) over delayed initiation, and
continuation of parenteral anticoagulation for a minimum
of 5 days and until the international normalized ratio (INR)
is 2.0 or above for at least 24 h (Grade 1B).
In patients with a high clinical suspicion of acute VTE, we
suggest treatment with parenteral anticoagulants
compared with no treatment while awaiting the results of
diagnostic tests (Grade 2C).
•
Guyatt GH, et al. CHEST. 2012;141(2 Suppl):7S–47S.
43
VTE Treatment 2012 ACCP
Recommendations/Suggestions
• In patients with acute DVT of the leg, we suggest
•
LMWH or fondaparinux over IV UFH (Grade 2C) and
over SC UFH (Grade 2B for LMWH; Grade 2C for
fondaparinux).
In patients with acute DVT of the leg treated with
LMWH, we suggest once- over twice-daily
administration (Grade 2C).
Guyatt GH, et al. CHEST. 2012;141(2 Suppl):7S–47S.
44
VTE Treatment 2012 ACCP
Recommendations/Suggestions
• In patients with acute DVT of the leg and whose home
•
circumstances are adequate, we recommend initial
treatment at home over treatment in hospital (Grade 1B).
In patients with acute DVT of the leg, we recommend
against the use of an IVC filter in addition to
anticoagulants (Grade 1B) .
Guyatt GH, et al. CHEST. 2012;141(2 Suppl):7S–47S.
45
© 2012 by the American Pharmacists Association. All rights reserved. Printed in the U.S.A.
VTE Treatment 2012 ACCP
Recommendations/Suggestions
• In patients with acute proximal DVT of the leg and
•
contraindication to anticoagulation, we recommend the
use of an IVC filter (Grade 1B).
In patients with acute proximal DVT of the leg and an
IVC filter inserted as an alternative to anticoagulation,
we suggest a conventional course of anticoagulant
therapy if their risk of bleeding resolves (Grade 2B).
Guyatt GH, et al. CHEST. 2012;141(2 Suppl):7S–47S.
46
VTE Treatment 2012 ACCP
Recommendations/Suggestions
• In patients with a proximal DVT of the leg provoked by
surgery, we recommend treatment with anticoagulation
for 3 months over (i) treatment of a shorter period
(Grade 1B), (ii) treatment of a longer time-limited
period (e.g., 6 or 12 months) (Grade 1B), or (iii)
extended therapy (Grade 1B regardless of bleeding
risk).
Guyatt GH, et al. CHEST. 2012;141(2 Suppl):7S–47S.
47
VTE Treatment 2012 ACCP
Recommendations/Suggestions
• In patients with a proximal DVT of the leg provoked by
a nonsurgical transient risk factor, we recommend
treatment with anticoagulation for 3 months over (i)
treatment of a shorter period (Grade 1B), (ii) treatment
of a longer time-limited period (e.g., 6 or 12 months)
(Grade 1B),and (iii) extended therapy if there is a high
bleeding risk (Grade 1B). We suggest treatment with
anticoagulation for 3 months over extended therapy if
there is a low or moderate bleeding risk (Grade 2B).
Guyatt GH, et al. CHEST. 2012;141(2 Suppl):7S–47S.
48
© 2012 by the American Pharmacists Association. All rights reserved. Printed in the U.S.A.
VTE Treatment 2012 ACCP
Recommendations/Suggestions
• In patients with an unprovoked proximal DVT of the leg,
we recommend treatment with anticoagulation for at least
3 months over treatment of a shorter duration (Grade
1B). After 3 months of treatment, patients with
unprovoked DVT of the leg should be evaluated for the
risk-benefit ratio of extended therapy.
In patients with a first VTE that is an unprovoked
proximal DVT of the leg and who have a low or moderate
bleeding risk, we suggest extended anticoagulant
therapy over 3 months of therapy (Grade 2B).
•
Guyatt GH, et al. CHEST. 2012;141(2 Suppl):7S–47S.
49
Technical Advisory Panel to TJC/NQF
•
•
•
•
•
•
•
•
•
•
•
•
•
•
•
Dale Bratzler, DO, MPH*
Stephen V. Cantrill, MD
Joseph A. Caprini, MD, MS, RVT*
Vanessa K. Dalton, MD, MPH
John A. Heit, MD*
William H. Geerts, MD*
Samuel Z. Goldhaber, MD*
James B. Groce III, PharmD
Scott Kaatz, DO*
Nicolas Labropoulos, PhD, DIC, RVT
Franklin A. Michota Jr., MD
Ruth Morrison, BSN, CVN
Victor F. Tapson, MD*
Alexander G. Turpie, MB*
Suresh Vedantham, MD
50
VTE Treatment 2012 ACCP
Recommendations/Suggestions
Core Measure
Description
VTE Prophylaxis
Upon admission, patients are to be
given prophylaxis or have
documentation why NO prophylaxis
was given within 24 hours of
admission or surgery end time
ICU Prophylaxis
Receive or show documentation why
NO prophylaxis was given within 24
hours of admission or transfer to ICU
Incidence of potentially preventable
VTE
Patients who are diagnosed with
VTE during hospitalization (not
present on admission) that did not
receive prophylaxis
Members Eight ACCP Conference on Antithrombotic and Thrombolytic Therapy.
CHEST.2008
51
© 2012 by the American Pharmacists Association. All rights reserved. Printed in the U.S.A.
VTE Prophylaxis 2012 ACCP
Recommendations/Suggestions
• For acutely ill hospitalized medical patients at
increased risk of thrombosis, we recommend
anticoagulant thromboprophylaxis with lowmolecular-weight heparin [LMWH], low-dose
unfractionated heparin (LDUH) bid, LDUH tid,
or pentasaccharide (Grade 1B).
Kahn SR, et al. CHEST. 2012;141;e195S-e226S.
52
VTE Prophylaxis 2012 ACCP
Recommendations/Suggestions
• For acutely ill hospitalized medical patients at
increased risk of thrombosis who are bleeding or are at
high risk for major bleeding, we suggest the optimal
use of mechanical thromboprophylaxis with graduated
compression stockings (GCS) (Grade 2C) or
intermittent pneumatic compression (IPC) (Grade 2C),
rather than no mechanical thromboprophylaxis. When
bleeding risk decreases, and if VTE risk persists, we
suggest that pharmcologic thromboprophylaxis be
substituted for mechanical thromboprophylaxis (Grade
2B).
Kahn SR, et al. CHEST. 2012;141;e195S-e226S.
53
VTE Prophylaxis 2012 ACCP
Recommendations/Suggestions
• For general and abdominal-pelvic surgery patients at
moderate risk for VTE (~ 3.0%; Rogers score, >10; Caprini
score, 3-4) who are not at high risk for major bleeding
complications, we suggest LMWH (Grade 2B), LDUH
(Grade 2B), or mechanical prophylaxis, preferably with IPC
(Grade 2C), over no prophylaxis.
• Remarks: Three of the seven authors favored a strong
(Grade 1B) recommendation in favor of LMWH or LDUH
over no prophylaxis in this group.
Kahn SR, et al. CHEST. 2012;141;e195S-e226S.
54
© 2012 by the American Pharmacists Association. All rights reserved. Printed in the U.S.A.
VTE Prophylaxis 2012 ACCP
Recommendations/Suggestions
• For general and abdominal-pelvic surgery patients at
moderate risk for VTE (3.0%; Rogers score, >10;
Caprini score, 3-4) who are at high risk for major
bleeding complications or those in whom the
consequences of bleeding are thought to be
particularly severe, we suggest mechanical
prophylaxis, preferably with IPC, over no prophylaxis
(Grade 2C).
Kahn SR, et al. CHEST. 2012;141;e195S-e226S.
55
VTE Prophylaxis 2012 ACCP
Recommendations/Suggestions
• For general and abdominal-pelvic surgery patients at
high risk for VTE (~ 6.0%; Caprini score, ≥5) who are
not at high risk for major bleeding complications, we
recommend pharmacologic prophylaxis with LMWH
(Grade 1B) or LDUH (Grade 1B) over no prophylaxis.
We suggest that mechanical prophylaxis with elastic
stockings or IPC should be added to pharmacologic
prophylaxis (Grade 2C).
Kahn SR, et al. CHEST. 2012;141;e195S-e226S.
56
VTE Prophylaxis 2012 ACCP
Recommendations/Suggestions
• For high-VTE-risk patients undergoing abdominal or
•
pelvic surgery for cancer who are not otherwise at high
risk for major bleeding complications, we recommend
extended-duration pharmacologic prophylaxis (4
weeks) with LMWH over limited-duration prophylaxis
(Grade 1B).
Remarks: Patients who place a high value on
minimizing out-of-pocket health-care costs might prefer
limited-duration over extended-duration prophylaxis in
settings where the cost of extended-duration
prophylaxis is borne by the patient.
Kahn SR, et al. CHEST. 2012;141;e195S-e226S.
57
© 2012 by the American Pharmacists Association. All rights reserved. Printed in the U.S.A.
Learning Objectives
• At the completion of this application-based activity,
pharmacists will be able to:
– Identify the current challenges in clinical practice related to
anticoagulation therapy.
– Explain the mechanism of action of warfarin, direct Factor
Xa inhibitors and direct Factor IIa inhibitor drug therapies.
– Describe the management and
recommendations/suggestions of selected situations
requiring antithrombotic therapy, including atrial fibrillation,
deep venous thrombosis and pulmonary embolism.
– Evaluate patient cases that address current challenges in
clinical practice and selected situations and provide
treatment recommendations based on current evidence and
emerging information.
– Develop an individualized patient care plan which should
include a patient specific dosing regimen, monitoring
parameters, and treatment goals.
58
Case 1
• NG is a 58 year-old woman seen in the outpatient
clinic with the following documented problems:
–
–
–
–
–
–
–
History of cellulitis, recurring (ICD-682.7)
History of blood in stool (ICD-578.1)
History of URI, acute (ICD-465.9)
History of rectal bleeding (ICD-569.3)
History of pulmonary embolism (ICD-V415.11)
History of atrial fibrillation, paroxysmal (ICD-427.31)
History of COPD (ICD-496)
URI=upper respiratory infection.
COPD=chronic obstructive pulmonary disease.
59
Case 1
Medication
Start Date
End Date
Jul 10, 2009
Jul 12, 2009
Ciprofloxacin
Nov 16, 2009
Nov 19, 2009
Phytonadione
Nov 16, 2009
Doxycycline
Nov 19, 2009
Prednisone
Jan 4, 2010
Jan 19, 2010
Moxifloxacin
Jan 4, 2010
Jan 19, 2010
Doxycycline
May 21, 2010
May 26, 2010
Moxifloxacin
Jul 8, 2010
Jul 18, 2010
Ciprofloxacin
Jul 26, 2010
Jul 30, 2010
Nitrofurantoin
Aug 13, 2010
Aug 15, 2010
Doxycycline
Aug 13, 2010
Aug 23, 2010
Azithromycin
Sep 13, 2010
Sep 18, 2010
Metronidazole
Nov 24, 2009
60
© 2012 by the American Pharmacists Association. All rights reserved. Printed in the U.S.A.
Case 1
INR Graph for NG: Target range is 2.0-3.0
9
8
INR
7
6
5
4
3
2
1
Nov 1
Jan 1
Mar 1
May 1
Jul 1
Sept 1
Nov 1
INR Measurement Date
INR=international normalized ratio.
Jan 1
61
Case 1
• January 17, 2011 patient with INR <2.0 was
•
•
converted from warfarin to oral direct thrombin
inhibitor-dabigatran
Patient has been followed weekly via telemanagement as well as follow-up OPC visits
Patient is doing well
OPC=outpatient clinic.
62
Learning Objectives
• At the completion of this program, participants will be
able to:
– Identify the current challenges in clinical practice related to
anticoagulation therapy.
– Explain the mechanism of action of warfarin, direct Factor
Xa inhibitors and direct Factor IIa inhibitor drug therapies.
– Describe the management and
recommendations/suggestions of selected situations
requiring antithrombotic therapy, including atrial fibrillation,
deep venous thrombosis and pulmonary embolism.
– Evaluate patient cases that address current challenges in
clinical practice and selected situations and provide
treatment recommendations based on current evidence and
emerging information.
– Develop an individualized patient care plan which should
include a patient specific dosing regimen, monitoring
parameters, and treatment goals.
63
© 2012 by the American Pharmacists Association. All rights reserved. Printed in the U.S.A.
Case 2
•
•
•
•
•
Date of visit: Jan 9, 2012
Primary Care Provider: Jessica Watson, MD
CC: vaginal bleeding and lower abdominal pain.
History of Present Illness:
50 yo African American woman with Past Medical History of asthma, and
bipolar disorder who presents for follow-up of R ovarian vein thrombosis
and ongoing vaginal bleeding. She was seen in Wesley Long ED last night
with pelvic/lower abdominal pain and vaginal bleeding that has been
ongoing since 12/23/2011. She was found to have R ovarian vein
thrombosis on CT. Was started on warfarin and enoxaparin. Seen by Dr
Groce earlier this afternoon for management of anticoagulation. Vaginal
bleeding has persisted unchanged since starting anticoagulation; soaking
through a feminine pad in 1 hour at its worst and merely spotting at its best.
Hb in the ED last night was 14. However, patient reports feeling weaker and
more fatigued which she attributes to this long period of bleeding. She is
very frustrated and worried about the persistent bleeding and is anxious for
it to resolve.
64
Case 2
•
•
•
•
•
•
•
•
•
•
•
Impression & Recommendations:
Problem # 1: ABNORMAL VAGINAL BLEEDING (ICD-626.9)
Assessment: New
Ongoing since 12/23/2011 and quite heavy at times. Increasingly concerned about
ongoing bleeding in setting of anticoagulation for ovarian vein thrombosis. Not a
candidate for esterogen therapy b/c of active thrombosis. Will order transvaginal
ultrasound and refer to GYN for further evaluation -- patient will need to be seen
ASAP. She also will need close monitoring because of ongoing blood loss on
anticoagulation.
Orders:
Ultrasound (Ultrasound)
Gynecologic Referral (Gyn)
Problem # 2: DVT (ICD-453.40)
Assessment: New
On warfarin and enoxaparin for treatment of ovarian vein thrombosis. Followed by
Dr. Groce in anticoagulation clinic. Will refer to GYN as above. Will give Toradol
(ketorolac) injection in clinic to help manage pain.
The patient was commenced upon warfarin 5 mg po qd and concomitant enoxaparin
at treatment dose(s) 1 mg/kg sq q12h. The following warfarin dose(s)/dosing and
subsequent INR determinations were observed in reverse chronologic order. 65
Case 2
Date
INR
*Mg in/tablet
strength
01/24/2012
11:48AM
0.9
01/17/2012
01:52PM
Variables
Actions
*Mg
out/tablet
strength
15 mg/ (5 mg) Factor X clotting factor assay
daily as
77% (normal 72% -134%)
3x5mg tablets
Warfarin assay 1.3 mcg/mL
(normal 1.0–10.0 mcg/mL)
[indicative of compliance]
Increase
dose,
Continue
LMWH
20 mg/(5
01/30/12
mg) daily
as 4x5 mg
tablets
0.9
12.5 mg (5
mg) daily as
2&1/2 x 5 mg
tablets
Increase
dose,
Continue
LMWH
15 mg/ (5 01/24/12
mg) daily
as 3x5 mg
tablets
01/12/12
11:45AM
1.0
10 mg (5 mg)
daily as 2x5
mg tablets
Increase
dose,
Continue
LMWH
12.5 mg
01/17/09
(5 mg)
daily as
2&1/2 x 5
mg tablets
01/09/12
9:30AM
1.0
10 mg; 7.5
mg/5 mg on
1st/2nd/3rd day
First INR as an OP having
been just discharged from ED
as outpatient on warfarin +
LMWH 1 mg/kg sq q12h
Next INR
Increase
dose,
Continue
LMWH
66
© 2012 by the American Pharmacists Association. All rights reserved. Printed in the U.S.A.
Genetic Polymorphisms and Warfarin
Therapy
Caucasians
Native Canadians
African Americans
Asians
CYP2C9*1
CYP2C9*2
CYP2C9*3
79%-89%
91%
98%
95%-98%
8%-19%
3%
1.5%-3.6%
0%
6%-10%
6%
0.5%-1.5%
1.7%-5%
KORC1 Haplotypes2
H1H2
H8H9
37%
58%
14%
49%
89%
10%
Euro Americans
African Americans
Asian Americans
1Takahashi
2Rieder.
H, et al. Clin Pharmacokinet. 2001;40:587-603.
MJ, et al. N Engl J Med. 2005;352:2285-2293.
67
Dosing Recommendations With
Consideration of Genotype
•If the patient’s CYP2C9 and/or VKORC1 genotype are known,
consider these ranges in choosing the initial dose.
•Patients with CYP2C9 *1/*3, *2/*2, *2/*3, and *3/*3 may
require more prolonged time (>2 to 4 weeks) to achieve
maximum INR effect for a given dosage regimen than patients
without these CYP variants.
http://packageinserts.bms.com/pi/pi_coumadin.pdf Accessed Feb 18, 2012.
68
Reimbursement of Genetic Testing
• Reimbursement depends upon the
patient’s coverage—patient is
responsible for any uncovered
balance(s)
• As of April 2010, Medicare is only
reimbursing for the warfarin genetic
testing for those patients enrolled in a
clinical trial
https://www.cms.gov/MLNMattersArticles/downloads/MM6715.pdf.
Accessed Feb 17, 2012.
69
© 2012 by the American Pharmacists Association. All rights reserved. Printed in the U.S.A.
Anticoagulant Pipeline and Anticipated
Indications (Projected)
MOA
2010
2011
2012
2013
Hip & knee
AF
Med ill
ACS
VTE
Med ill, VTE
(2Q)
AF (3Q)
Hip & knee (4Q)
ACS
Rivaroxaban
Xa
Dabigatran
DTI
Apixaban
Xa
Betrixaban
Xa
Hip & knee
Edoxaban
Xa
AF, VTE
Ticagrelor
ADP
TRA-SCH
TRA
Clopidogrel*
ADP
AF
2014
Hip & knee
AF
ACS
ACS
ACS/NSTEMI
AF
ACS=acute coronary syndrome.
ADP=adenosine diphosphate.
AF=atrial fibrillation.
DTI=direct thrombin inhibitor.
MOA=mechanism of action.
NSTEMI=non-ST segment elevation
myocardial infarction.
TRA=thrombin-receptor antagonists.
VTE=venous thromboembolism.
Xa=direct factor Xa inhibitors.
*Patent expiry: November 2011.
Adapted from Weitz JI. Thromb Haemost. 2007;5 suppl 1:65-7.
70
Case 3
• Your patient who has been on warfarin
comes to your pharmacy with a new
prescription for a new oral
anticoagulant—dabigatran.
• The patient asks for your advice
regarding when to stop the warfarin—
and when to commence the new oral
anticoagulant
• Your response/advice?
71
Individualized Patient Care Plan
• Converting from warfarin to dabigatran
– Discontinue warfarin
– Start with dabigatran when INR <2.0
INR=international normalized ratio.
Dabigatran etexilate prescribing information. Boehringer Ingelheim Pharmaceuticals, Inc. January 2012.
72
© 2012 by the American Pharmacists Association. All rights reserved. Printed in the U.S.A.
Case 4
• Your patient who has been on
dabigatran comes to your pharmacy
with a new prescription for a warfarin
• The patient asks for your advice
regarding when to stop the
dabigatran—and when to commence
warfarin
• Your response/advice?
73
Individualized Patient Care Plan
• Converting from dabigatran to warfarin
Creatinine Clearance Recommended Starting Time of Warfarin
>50 mL/min
3 days before discontinuing dabigatran
31-50 mL/min
2 days before discontinuing dabigatran
15-30 mL/min
1 day before discontinuing dabigatran
<15 mL/min
No recommendations can be made
INR=international normalized ratio.
Dabigatran etexilate prescribing information. Boehringer Ingelheim Pharmaceuticals, Inc. January 2012.
74
Case 5/6
• Your patient who has been on warfarin comes to
•
your pharamcy indicating that he has elected to
commence rivaroxaban
– He asks your advice about “…how to
transition… do I just stop the warfarin and start
rivaroxaban?”
Your patient who has been on rivaroxaban comes
to your pharmacy indicating that he has elected to
go back on warfarin therapy
– He asks your advice about “…how to
transition… do I just stop the rivaroxaban and
start warfarin?”
75
© 2012 by the American Pharmacists Association. All rights reserved. Printed in the U.S.A.
Individualized Patient Care Plan
rivaroxaban  warfarin
warfarin rivaroxaban
Discontinue warfarin
Initiate rivaroxaban
when the INR is below
3.0 to avoid
inadequate
anticoagulation
There are no clinical trial data
to guide converting from
rivaroxaban to warfarin
One approach is to discontnue
rivaroxaban and begin both a
parenteral anticoagulant and
warfarin when the next
rivaroxaban dose would have
been taken*
*The recommendation to use a parenteral anticoagulant together with warfarin after discontinuing
rivaroxaban
is analogous to the bridging protocol recommended for starting moderate- to high-risk patients on warfarin.
Fuster V, et al. J Am Coll Cardiol. 2011;57(11):e101-e198.
76
Individualized Patient Care Plan
discontinuation was not
stipulated in ROCKET AF
• Warfarin patients who
completed the study were
generally maintained on
warfarin
• Rivaroxaban patients were
generally switched to
warfarin
No. of Strokes
• Anticoagulation after
– There was no
coadministration of warfarin
and rivaroxaban
– This resulted in inadequate
anticoagulation after
stopping rivaroxaban until
attaining a therapeutic INR
Rivaroxaban
(n=4637)
Patel MR, et al. N Engl J Med. 2011;365(10):883-891.
Warfarin
(n=4691)
77
Key Points
• Short half-life of oral anticoagulants makes
adherence important
• No coagulation testing
• Less time and travel
• No finger stick or venipuncture
• Fixed dose: no dose finding
– Primary Care or Cardiology
• Simplifies responsibility
• Fewer strengths
• Possible decease in dosing errors
• Diet
• Less effect
78
© 2012 by the American Pharmacists Association. All rights reserved. Printed in the U.S.A.
Self-Assessment Question
• What is an appropriate quality
marker for anticoagulation
management for patients
maintained on warfarin?
79
Self-Assessment Question
• How will we develop quality and
assess quality for the new oral
anticoagulants?
80
Self-Assessment Question
• What is desired in an
anticoagulant that will help us, as
pharmacists, help the physician—
and ultimately help the patient?
81
© 2012 by the American Pharmacists Association. All rights reserved. Printed in the U.S.A.
Self-Assessment Questions
• When you dispense an oral anticoagulant—
•
•
do you know the indication for which it has
been prescribed?
When you dispense an oral anticoagulant—
do you know the patient’s renal function?
When you dispense an oral anticoagulant—
do you know the seriousness of the
potential for drug-drug interaction(s)?
82
QUESTIONS AND ANSWERS
83
© 2012 by the American Pharmacists Association. All rights reserved. Printed in the U.S.A.
Notes
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© 2012 by the American Pharmacists Association. All rights reserved. Printed in the U.S.A.