WHY
ANTICOAGULATION?
Jean M. Connors, MD
Assistant Professor of Medicine
Medical Director, Anticoagulation Management Services
Hematology Division
Thrombosis
• Thrombosis (Greek: θρόμβωσις) is the
formation of a blood clot (thrombus; Greek:
θρόμβος) inside a blood vessel, obstructing
the flow of blood through the circulatory
system. When a blood vessel is injured, the
body uses platelets and fibrin to form a blood
clot to prevent blood loss. Even when a blood
vessel is not injured, blood clots may form in
the body under certain conditions. A clot that
breaks free and begins to travel around the
body is known as an embolus
http://en.wikipedia.org/wiki/Main_Page
Hemostasis
Pro-clotting <----------> Anti-clotting
anticoagulation
Virchow's triad
Kyrle P A , Eichinger S Blood 2009;114:1138-1139
©2009 by American Society of Hematology
Upsetting the Balance
• Atrial fibrillation--irregular heart
rhythm
• Blood pools and slows in the atrium and
forms clots
• Clots can travel out of the heart, results in
“thromboembolism” usually arterial
–Mechanical heart valves
• Artificial surface activates clotting factors
and platelets, also a mechanism of arterial
thromboembolism
The Heart
The Heart
Upsetting the Balance
• Atrial fibrillation--irregular heart
rhythm
• Blood pools and slows in the atrium and
forms clots
• Clots can travel out of the heart, results in
“thromboembolism” usually arterial
–Mechanical heart valves
• Artificial surface activates clotting factors
and platelets, also a mechanism of arterial
thromboembolism
The Heart
The Heart
Upsetting the Balance
• Stroke
• Atherosclerosis: carotid artery plaques
• Cardiac thrombosis
– Congestive heart failure
• Arterial thromboembolic events without
obvious cause
Major Veins and Arteries
Major Veins and Arteries
Leg Veins
Upsetting the Balance
• Venous thromboembolism (VTE)
– Deep vein
– Superficial vein
– Pulmonary embolus
• Risks:
– Surgery
– Orthopedic joint replacement surgery
• Hips, knees
– Trauma surgery for fractures
– Bed rest/hospitalization
Upsetting the Balance
• Risks for blood clots
– Cancer
• Certain kinds or certain treatments
• Usually venous but sometimes arterial
– Antiphospholipid syndrome
• Auto-immune disorder, both venous and arterial
clots
– Inherited blood clotting disorders
•
•
•
•
•
Factor V Leiden
Prothrombin gene mutation
Protein S deficiency
Protein C deficiency
Antithrombin deficiency
What
is
Anticoagulation?
What is anticoagulation?
• Use of prescription medications that make
your blood less likely to clot.
• These medications are called
anticoagulants.
• Also known as “blood thinners” or “anticlotting medicines.” They make it harder to
form a clot.
Goals
of
Anticoagulation
Goals of anticoagulation
• Prevent a new blood clot from getting
bigger
• Prevent a recurrent blood clot
• “Prophylaxis”—preventing a blood
clot in someone is who at high risk for
having a blood clot but has never had
one
How
Long?
Goals of anticoagulation
• Depends on the “risk factor” or reason
– Temporary risks or “provoked” blood clots can
be treated with limited duration of
anticoagulation
• After surgery
– Permanent risks, or unprovoked blood clots,
often require “indefinite”, lifelong, continued
anticoagulation
• Atrial fibrillation
ANTICOAGULANTS
OLD
– 1922 Heparin: first anticoagulant developed
for human use
– 1954 Warfarin: first oral anticoagulant
IN BETWEEN
– 1996 LMWH= Lovenox, Fragmin
– 2001 Fondaparinux=Arixtra
NEW ORAL ANTICOAGULANTS
– 2010 Dabigatran=Pradaxa
– 2011 Rivaroxaban=Xarelto
– 2013 Apixaban=Eliquis
What
Kind?
Goals of anticoagulation
• Different types depending on need:
• Intravenous
– Heparin
– Bivalirudin
– argatroban
• Subcutaneous injections
– Enoxaparin, dalteparin
– fondaparinux
• Oral
– Warfarin
– “new” oral anticoagulants
The End
• Talk to your health care providers:
– Physician
– Nurse, nurse practitioner, physician assistant
– BWH Anticoagulation Management Service
clinician
Importance of INR
Monitoring
Laura Hill RPh, Pharm D
Anticoagulation Clinic
Brigham and Women’s Hospital
Objectives
Define INR and how it relates to warfarin
Understand the importance of warfarin therapy and
the need for close INR monitoring
Appreciate what factors affect your INR level
Review the different ways to monitor your INR
What is an INR?
The International Normalized Ratio (INR) is a
measurement of how long it takes blood to form
a clot.
For most people, the INR result that provides
the best balance between the risk of bleeding
and clotting is between 2.0 and 3.0 – this is
called the “target INR range.”
How Does Warfarin Work?
Your body uses vitamin K to produce
some of the clotting factors that helps
blood to clot
Warfarin (Coumadin) works by
interfering with how your body uses
vitamin K
Goals of Warfarin Therapy
Decrease the time it takes the body to
form a clot
Fluctuations in INR
Prescription medications
Herbal supplements and vitamins
Medications you buy 'over the counter'
Diet
Health
Alcohol intake and/or smoking
Activity level
Target INR Ranges
Therapeutic Recommendations For Warfarin
Target INR Ranges
As your INR
increases your
risk of clotting
decreases
As your INR
increases your
risk for bleeding
increases
Critical INR values
INR > 4.0
risk of bleeding
INR < 1.5
risk of developing a clot
How Often to Test INR
How often you test your INR will vary from person
to person.
Extra tests may be required in certain situations.
For instance, a change in medication may affect
your warfarin metabolism and alter your INR.
Warfarin Dosage Requirements
Your target warfarin dose depends on many
factors, including genetics, and is unique to
each individual.
For one person, a small warfarin dose may be
enough to reach their target INR, while another
person may need to take 2-3 times (or more) as
much to achieve the same effect.
Options for Testing INR
Lab Testing:
Doctor’s office
Outpatient lab
VNA/Home draw services
Options for testing INR
Point-of-care testing:
Roche CoaguChek® XS INR system
Alere INRatio®2 PT/INR monitor
Travel and INR Monitoring
Test your INR before leaving on your trip
Keep your activity and eating habits as close
to your regular routine as possible
It may be possible to send an INR order to
the lab while you are away
Missed Doses and INR
Avoid missing doses of warfarin
Make warfarin a part of your daily routine
NEVER take a double dose!
Keeping INR Stable
Your keys to success:
Take your warfarin exactly as
prescribed.
Have your INR checked regularly.
Keep your vitamin K intake and activity
consistent from day to day.
Key Points in INR Monitoring
INR tests are conducted for your safety.
Take your warfarin exactly the way your
warfarin manager tells you.
Report any changes in medications, and any
significant changes in your daily routines and
diet, to your warfarin manager.
References
Ageno W, Gallus AS, Wittkowsky A, et al, “Oral Anticoagulant Therapy: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed:
American College of Chest Physicians Evidence-Based Clinical Practice Guidelines,” Chest, 2012, 141(2 Suppl):e44-88.
Optimal oral anticoagulant therapy in patients with nonrheumatic atrial fibrillation and recent cerebral ischemia. The European Atrial Fibrillation
Trial Study Group. N Engl J Med 1995; 333:5.
Jones M, McEwan P, Morgan CL, et al. Evaluation of the pattern of treatment, level of anticoagulation control, and outcome of treatment with
warfarin in patients with non-valvar atrial fibrillation: a record linkage study in a large British population. Heart 2005; 91:472.
White HD, Gruber M, Feyzi J, et al. Comparison of outcomes among patients randomized to warfarin therapy according to anticoagulant
control: results from SPORTIF III and V. Arch Intern Med 2007; 167:239.
Oake N, Jennings A, Forster AJ, et al. Anticoagulation intensity and outcomes among patients prescribed oral anticoagulant therapy: a
systematic review and meta-analysis. CMAJ 2008; 179:235.
http://www.mayoclinic.org/tests-procedures/prothrombin-time/basics/results/prc-20013300
http://www.ptinr.com/
Blann AD, Fitzmaurice DA, Lip GY; Anticoagulation in hospitals and general practice.; BMJ. 2003 Jan 18;326(7381):153-6.
Shalansky S, Lynd L, Richardson K, et al; Risk of warfarin-related bleeding events and supratherapeutic international normalized ratios
associated with complementary and alternative medicine: a longitudinal analysis. Pharmacotherapy. 2007 Sep;27(9):1237-47.
Brigham and Women’s Hospital
Anticoagulation Management Service
Living with Warfarin: What Affects your INR?
Gina Dube, PharmD, CACP, RPh
October 25, 2014
Objectives
 Identify the factors that influence the INR
 Understand ways to improve warfarin
therapy with lifestyle changes
 Identify disease states which may influence
warfarin therapy
What is Warfarin?
 Anticoagulant
– Medication that is used
to reduce the formation
of blood clots
 Commonly referred
to as a“blood
thinner”
– Increasing the time it
takes for blood clot
How Does Warfarin Work?
 Blocks a process
that uses Vitamin Kto make clotting
factors, therefore
reducing the body’s
ability to make blood
clots
Holmes, 2012
What Affects your INR?










Diet
Missed doses
Alcohol
Other Medications
Exercise
Illness/Infection
Dietary supplements
Vitamins
Smoking
Holding for procedures
44
Diet and Vitamin K
 Foods rich in Vitamin K can cause a decrease in your INR
You do not need to
eliminate Vitamin K
containing foods from your
diet
 Vitamin K foods have been shown to keep your
INR levels more stable
45
Vitamin K Content of Selected Vegetables
Description
Serving
Vitamin K
(mcg/measure)
VERY HIGH (>500mcg/serving)
Kale – cooked
1 cup
1062
Collards – frozen, cooked
1 cup
1059
Spinach – frozen, cooked
1 cup
1027
Beet greens – cooked
1 cup
697
Dandelion greens – cooked
1 cup
579
Turnip Greens – frozen,
cooked
1 cup
851
HIGH (200-500 mcg/serving)
Mustard greens – cooked
1 cup
419
Brussels sprouts – cooked
1 cup
300
Broccoli – cooked
1 cup
220
Onion – scallions, raw
1 cup
207
Diet and Vitamin K
Eating more Vitamin K foods than
usual can decrease your INR
Vitamin K
=
INR
Eating less Vitamin K foods than usual
can increase your INR
47
Diet and Vitamin K
 Consistency is the key!
– Your INR levels are based
on your current vitamin K
intake
– Call your warfarin
manager to report any
drastic changes in your
diet
48
What if I Forget to Take My Warfarin?
 If you remember later
the same day, take it
as soon as you
remember.
 If you don’t remember
until the next day, call
your warfarin manager.
 DO NOT TAKE
EXTRA DOSES
TO CATCH UP
49
Alcohol

Alcohol interferes with the liver’s ability to
breakdown warfarin
Alcohol

INR
Drinking more than 2 alcoholic drinks in one day
can increase your risk of serious bleeding while
taking warfarin
Alcohol
One alcoholic drink =
51
Drug Interactions
 Warfarin interacts with many medications
and supplements including:
– Prescription (e.g. Antibiotics, steroids….)
– Over-the -Counter Medications (e.g. Tylenol,
Advil, Aleve, Motrin…)
– Vitamins
– Herbal Supplements
– Dietary Supplements
52
Dietary Supplements
 Many supplements can interact with warfarin
 Some multi-vitamins and meal replacement shakes
contain vitamin K
 Consult your healthcare provider prior to starting
any supplements
Other Interactions
 Read all labels
 Nutritional
Supplements
– Bars
– Drinks
54
Drug Interactions
 Your current INR level is based on the
medications that you currently take.
 Notify your warfarin manager before you
START, STOP or CHANGE ANY
MEDICATIONS
 Warfarin can also interfere with the way other
medications work
55
Exercise and INR
 Increase or decrease in physical activity can alter
the INR level
  activity = INR
  activity =  INR
 BE CONSISTENT!
Illness
 Let your warfarin manager know if you experience
– vomiting
– diarrhea or constipation
– Cold, fever, flu
– Infection
– other serious illness
These symptoms may affect your INR and require a
warfarin dosage adjustment
57
Disease States and Warfarin
 Increased effect
 Decreased effect
– Hyperthyroidism
– Liver disease
– Crohn’s disease
– Congestive heart
failure
– Hypothyroidism
– Fat malabsorption
58
Smoking and INR
Cigarette smoking = INR
Cigarette smoking = INR
Notify your warfarin manager if you start
smoking or decide to quit smoking.
59
Procedures
 Communication with all providers
(doctors, dentists, pharmacists,
physical therapists, chiropractors)
60
Take Home Points
 Call your warfarin manager if you
– START, STOP or CHANGE ANY MEDICATIONS
– Experience any illnesses
– MISSED doses
– Schedule a procedure
 Be CONSISTENT with
– Vitamin K intake
– Alcohol consumption (Don’t drink in excess)
– Physical activity
61
References
 Holmes M, et al. The Role of Dietary Vitamin K in
the Management of Oral Vitamin K Antagonists.
Blood Reviews. 2012; 26: 1-14
 Shibata Y, et al. Influence of Physical Activity on
Warfarin Therapy. Thromb Haemost, 1998; 80:
203-4
 National Institutes of Health
– http://www.ods.od.nih.gov/factsheets/cc/coumadin1pdf
62
Brigham and Women’s Hospital
Anticoagulation Management Service
Thank you!
63
Patient Advocacy
Kathryn Mikkelsen
Director, NATF
Chair, NATF Patient Advocacy Committee
September 20, 2014
Need
• PE, stroke, and ACS are the top three
cardiovascular killers in the United States
Other
16.2%
Disease of the Arteries
3.4%
Coronary Heart Disease
49.0%
High Blood Pressure
7.8%
Heart Failure
7.2%
Stroke
16.4%
Need
NATF PAC Mission Statement
• The goal of the North American Thrombosis Forum (NATF)
Patient Advocacy Committee (PAC) is to provide education
and advocacy in support of patients with heart disease and
clotting disorders in alignment with NATF's vision to improve
patient care, outcomes, and public health. PAC strives to
bridge the gap in knowledge and understanding of these
disease states so patients can make informed decisions about
their health. Our membership is comprised of patients,
healthcare professionals, and industry leaders with the
mutual goal of improving patient outcomes through
awareness and education.
Committee Members
Current Initiatives
•
•
•
•
•
Patient Resources Redevelopment Project
Women’s Health Initiative
Minority Outreach Program
Support Groups
Speakers Bureau
Patient Resources Redevelopment
Project
Women’s Health Initiative
Minority Outreach Program
Support Groups
•Develop a micro-site on the NATF website specifically for women.
•Begin planning a live educational program
•Participate in community outreach events, such as health fairs, to promote the Women’s Health Initiative
Speakers Bureau
•Develop a micro-site on the NATF website specifically for women.
•Begin planning a live educational program
•Participate in community outreach events, such as health fairs, to promote the Women’s Health Initiative
Conclusion
• NATF is a unique organization that brings together
healthcare providers and patients.
• We are always looking for new members to join
NATF and the PAC.
• We would be happy to work with you to host an
educational event in your community.
• Visit the NATF website for reliable and up-to-date
information.
Need
• PE, stroke, and ACS are the top three
cardiovascular killers in the United States
Other
16.2%
Disease of the Arteries
3.4%
Coronary Heart Disease
49.0%
High Blood Pressure
7.8%
Heart Failure
7.2%
Stroke
16.4%
Brigham and Women’s Hospital
Anticoagulation Management Service
Home Testing and Self
Dosing
David DeiCicchi, Pharm.D, CACP, RPh
October 25th, 2014
Objectives
 Review different patient care models of
anticoagulation management and supporting data
 Introduce patient home testing and self dosing:
– definition
 Describe our education and training sessions for
patients
 Discuss how you can begin home testing and self
dosing
Patient Care Models
 Routine Medical Care (Usual Care)
– Anticoagulation management by a physician or staff
– Typically without systematic policies and follow up
 Anticoagulation Management Service (AMS)
– Managed by personnel dedicated to anticoagulation with
systematic policies in place to manage and dose patients
 Patient Self Testing (PST): Home Testing
– Use of point of care monitor to measure INR at home
– Dose managed by usual care or AMS
Patient Care Models
 Patient Self Management (PSM): Self dosing
– Testing your own INR and managing your own warfarin
dose based on your result
Van Walraven C et al. Effect of study setting on anticoagulation control: a
systematic review and metaregression. Chest. 2006;129(5):1155.
Home Testing
 Patient self-testing is an alternative to traditional
testing at a laboratory or physician’s office
 You will be supplied with a point of care device and
supplies to test your INR at home
 A small drop of blood from your finger is applied to
a test strip and the machine will generate an INR
within minutes
 BWH AMS will still manage your warfarin dosing
Why test at home?
 Improves quality of life and independence
 Promotes active involvement in your healthcare
 Alternative for patients with poor venous access
 More frequent monitoring leads to better control of
your anticoagulation therapy
 May decrease clotting and bleeding events by
increasing time spent in therapeutic range
Disadvantages of Home
Testing
 Potentially high cost of devices and test strips
 Difficulty performing the test
 Correlation with venipuncture varies from patient
to patient
 Decreased accuracy with some disease states
– Antiphospholipid antibody syndrome
Are home monitors accurate?
VP = 4.5
FS = 6.5
 Home results
correlate well with
laboratory results
 Any observed
difference is
reproducible
 Accuracy
decreases as the
INR increases
What machines are
available?
ProTime
INRatio 2
CoaguChek XS
• Analysis time: 3
to 5 minutes
• Test strips require
refrigeration
• Memory: 50 tests
• Plug or
rechargeable
battery
• Size: 9x4.5x3 in.
• Weight: 1.6 lbs.
• 15 µL blood
sample
• Analysis time: 1
minute
• Test strips at
room temperature
• Memory: 120
tests
• (4) AA batteries
• Size: 6x3x2 in.
• Weight: 9.3 oz.
with batteries
CoaguChek XS
• 27 µL blood
sample
INRatio2
PROtime
What are the differences?
• 8 µL blood
sample
• Analysis time: 1
minute or less
• Test strips at
room temperature
• Memory: 100
tests
• (4) AAA batteries
• Size: 5x3x1 in.
• Weight: 4.5 oz.
without batteries
* Only CoaguChek XS is insensitive to therapeutic doses of heparin/LMWH
How do I get a home INR
monitor?
 Discuss home testing with your warfarin manager
 Complete the online interactive training session
and fill out an application
 AMS physician prescribes meter and testing
supplies
 Monitor is delivered and training is scheduled
within 2 – 4 weeks
Education Session
Home Testing Process
What is patient self
dosing?
 PSM is the process of monitoring your
anticoagulation which includes:
– Testing your own international normalized ratio (INR)
with a point of care monitor
– Interpreting the blood result
– Managing your warfarin (Coumadin) dose based on your
(INR)
A medical facility trains the patient and oversees the
quality of anticoagulation using active surveillance
Why self dose?
 Improves quality of life and further achieves
independence
 Alternative for patients with limited time or
laboratory access
 Eliminates time for provider to patient contact with
dosing recommendations
 Promotes active involvement in your own health
care
PST With Or Without PSM
• Meta-analysis of 22
studies
•Compared to usual
care
• > 8,400 patients
Bloomfield et al. Annals of Internal Medicine. 2011;154:472-482.
Limitations
 Self monitoring requires proper identification and
education of suitable candidates
30-50% of patients chosen to self manage opted
out or were not able to self manage
How do I begin self
managing?
 You must be enrolled in BWH AMS
– Have a reliable mode of communication with AMS
 It is preferred that you utilize PST
– For at least 3 months time
 Discuss your candidacy with your warfarin manager
– PSM is not for everyone
 Sign up for a PSM workshop
– Receive self management training by an AMS clinician
PSM Workshop
 Dosing practice scenarios
 Documentation
– Recording INRs and dosing recommendations
 Identifying issues related to your anticoagulation
– Bleeding and clotting events
 Appropriate actions to take when an issue arises
– Reporting events and changes to AMS
– Present to the ED
Example of Dosing Card
Dosing Card
INR
Action
Less than 1.5
Call AMS
1.5 – 1.7
Increase 2 levels
1.8 – 1.9
Increase 1 level
2.0 – 3.0
Maintain level
3.1 – 3.5
Decrease 1 level
3.5 – 4.0
Decrease 2 levels
Greater then 4.0
Call AMS
Example of Dosing Card
Dosing Card
Level
Dose
Example
1
35mg/wk
5mg daily
2
36mg/wk
6mg Mon and 5mg others
3
38mg/wk
6mg Mon Wed Fri; 5mg rest of week
4
40mg/wk
5mg Mon Fri; 6mg rest of week
5
42mg/wk
6mg daily
6
44mg/wk
7mg Mon Fri; 6mg rest of week
7
46mg/wk
6mg Mon Wed Fri; 7mg rest of week
8
48mg/wk
6mg Sun; 7mg rest of week
9
51mg/wk
8mg Mon Fri, 7mg rest of week
Final Exam
 Once you have completed your workshop, you will
be required to give 4 consecutive approved dosing
recommendations prior to self managing.
 You will still need to:
–
–
–
–
report INRs to AMS
be available if AMS has questions or concerns
report any changes in your health or medications
inform us of any suspected bleeding or clotting events
Your Role In PSM
 You would be asked to:
– test your INR with a home machine at least twice
a month and report all results
– adjust your warfarin dose using your dosing card
– document INRs and dosing
– report any major changes that can affect your
INR
– report bleeding or clotting events
Our Role in PSM
 We are still fully responsible for your anticoagulation
management
 Your warfarin manager will always practice active
surveillance
 We are still available for any questions or dosing
consults if needed
 AMS will continue to write prescriptions
Summary
 Patient home testing and self dosing is a safe
alternative to warfarin management
 These patient care models can increase your
time spent in your therapeutic range and
decrease complications of anticoagulation
therapy
 You can become more reliant on yourself and
experience greater independence while on
warfarin
 Become PRO-active in your warfarin therapy
Brigham and Women’s Hospital
Main Anticoagulation Management Service
Thank you!
Questions?
Alternative Oral Anticoagulants
Nicholas Feola, PharmD, CACP, RPh
Brigham and Women’s Hospital Anticoagulation Service
Patient Seminar
October 25, 2014
Objectives
 Discuss the benefits and challenges of warfarin
 Identify the properties of “ideal” anticoagulants
 Compare the efficacy and safety of new oral
anticoagulants (NOACs) with warfarin
 Choose the best anticoagulant based on
specific patient characteristics
What is an Anticoagulant?
 Anticoagulant
– Medication that affects the blood’s ability to
form a blood clot
 Stops an existing clot from becoming
worse and prevents future clots from
forming
 Delay clotting time by targeting different
enzymes within clotting cascade
Types of Anticoagulants
 Oral
–
–
–
–
–
Warfarin
Rivaroxaban
Apixaban
Edoxaban
Dabigatran
 Intravenous
– Unfractionated heparin
– Bivalirudin
– Argatroban
 Subcutaneous
–
–
–
–
Unfractionated heparin
Enoxaparin
Daltaparin
Fondaparinux
Benefits of Warfarin
 Long track record
– First used in 1954
 Rapid turnaround
genetic testing
 Proven efficacy
 Point-of-care testing
 Centralized
anticoagulation
clinics
 Low cost
– Time in Therapeutic
Range (TTR) >60%
Challenges with Warfarin
 Requires frequent monitoring due to:
– Narrow therapeutic window
– Unpredictable pharmacology
 Multiple drug–drug and food–drug
interactions
 Increased risk of major and minor bleeds
Properties of an Ideal
Anticoagulant
Properties
Benefit
Oral, once daily dosing
Ease of administration
Rapid onset of action
No need for overlapping injectable
anticoagulant
Minimal food or drug interactions
Simplified dosing
Predictable anticoagulant effect
No coagulation monitoring
Extra renal clearance
Safe in patients with renal disease
Rapid offset of action
Simplifies management in case of
bleeding or intervention
Antidote
For emergencies
Eikelboom 2010
Properties of an Ideal
Anticoagulant
Properties
Dabigatran
(Pradaxa®)
Rivaroxaban
(Xeralto®)
Apixaban
(Eliquis®)
Edoxaban
(Savaysa®)
Oral, once
daily dosing
NO
YES/NO
(depends on
indication)
NO
YES
Rapid onset of
action
YES
YES
YES
YES
Minimal
interactions
YES
YES
YES
YES
Predictable
effect
YES
YES
YES
YES
Extra renal
clearance
NO
NO
NO
NO
Rapid offset of
action
YES
YES
YES
YES
Antidote
NO
NO
NO
NO
FDA Approved Indications
Indication
Dabigatran
(Pradaxa®)
Post-op Orthopedic
Prevention
Treatment of Deep Vein
Thrombosis (DVT)
√
(2014)
Rivaroxaban
(Xeralto®)
Apixaban
(Eliquis®)
√
(2011)
√
(2013)
√
(2012)
√
(2014)
Treatment of Pulmonary
Embolism (PE)
√
(2014)
√
(2012)
√
(2014)
Non-Valvular Atrial
Fibrillation
√
(2010)
√
(2011)
√
(2012)
Prevention of recurrence
DVT/PE
√
(2014)
√
(2012)
√
(2014)
Edoxaban
(Savaysa®)
Pending
FDA
Approval
Who Should NOT Use NOACs
 DO NOT use if you have a prosthetic heart
valve
– Increased risk of thromboembolic and bleeding
events with dabigatran
– Other medications not tested
 DO NOT use if you:
– Have severe kidney dysfunction
Measuring Anticoagulant
Effect
 Not required for routine dose adjustment
 None of the current tests are suitable for
quantifying anticoagulant effect
 Can determine if medication present
–
–
–
–
Prior to emergency procedures
In case of bleeding
In case of potential drug interaction
To verify compliance
Options for Reversing Effects
 No specific antidote at this time
 Activated charcoal within 2-3 hours if
overdose
 General supportive care
– Fluids, PRBCs, local measures, surgical
intervention
 Discontinue and allow effects to wear off
 Dialysis
 Various blood products
How effective and safe are the
NOACs compared to warfarin?
Effectiveness: Stroke
Prevention
• Decrease incidence of strokes or embolic events with NOACs
compared to warfarin
Re-ly = dabigatran; Rocket-AF= rivaroxaban; Aristotle = apixaban; Engage AF = edoxaban
Ruff 2014
Safety: Stroke Prevention
Major Bleeding
• Decreased incidence of major bleeding events with NOACs
•Higher incidence of Gastrointestinal bleeding with NOACs
Re-ly = dabigatran; Rocket-AF= rivaroxaban; Aristotle = apixaban; Engage AF = edoxaban
Ruff 2014
Efficacy: Treatment of DVT/PE
• Similar incidence of recurrent VTE, fatal PE or overall
mortality with NOACs compared to warfarin
Van der Hulle 2014
Safety: Treatment of DVT/PE
• Decreased incidence of major/fatal bleeding events with NOACs
•Similar incidence of Gastrointestinal bleeding with NOACs
Van der Hulle 2014
Which Anticoagulant to
Choose?
 Should be based on patient specific criteria
Patient Characteristic
Anticoagulant
Mechanical valve
Warfarin
Poor Compliance
Warfarin
Stroke while on warfarin
Dabigatran or apixaban
Stable on warfarin
Warfarin/consider switch to NOAC
Kidney problems
Warfarin
Dyspepsia/GI upset
Any except dabigatran
Recurrent GI bleeding
Apixaban
Once daily dosing
Warfarin or Rivaroxaban
Weitz 2012
Switching between
Anticoagulants
• Always consult warfarin manager or
physician
• High risk for clotting and bleeding during
transition
Limit time without
anticoagulation
Limit overlapping
effects
Switching Between
Anticoagulants
 Important to check INR result prior to switch
INR
<2.0
Dabigatran
Warfarin
INR
<3.0
Rivaroxaban
INR
<2.0
Apixaban
Limitations of NOACs
 No reversal agent
 Narrow scope compared to warfarin
 No long-term data
– Only 4-5years of information versus decades
with warfarin
 Cost
– Higher co-pays for insurance
Take Home Points
 Warfarin remains an effective treatment option, but
challenges include frequent monitoring and multiple
interactions with drugs, disease states, and lifestyle
 The NOACs provide alternative anticoagulation options with
minimal interactions and no need for laboratory monitoring
 The NOACs have equal or superior effectiveness compared
with warfarin with a favorable safety profile
 Discuss with your physician if you will benefit from
switching to NOAC
References
 Eikelboom JW, Weitz JI. New Anticoagulants. Circulation 2010; 121:
1523-1532
 Weitz JI, Gross PL. New Oral Anticoagulants: Which One Should my
Patient Use?. American Society of Hematology. 2012. 536-540
 Ruff CT, Giugliano RP, et al. Comparison of the efficacy and safety of
new oral anticoagulants with warfarin in patients with atrial fibrillation: a
meta-analysis of randomised trials. Lancet. 2014; 383:955-962
 Van der Hulle T, Kooiman P, et al. Effectiveness and safety of novel
oral anticoagulants as compared with vitamin K antagonists in the
treatment of acute symptomatic venous thromboembolism: a systematic
review and meta-analysis. J Thromb Haemost. 2014; 12:320-8
Brigham and Women’s Hospital
Main Anticoagulation Management Service
Thank you!
Questions?
FDA Approved Indications
Indication
Dabigatran
(Pradaxa®)
Post-op Orthopedic
Prevention
Treatment of Deep Vein
Thrombosis (DVT)
√
(2014)
Rivaroxaban
(Xeralto®)
Apixaban
(Eliquis®)
√
(2011)
√
(2013)
√
(2012)
√
(2014)
Treatment of Pulmonary
Embolism (PE)
√
(2014)
√
(2012)
√
(2014)
Non-Valvular Atrial
Fibrillation
√
(2010)
√
(2011)
√
(2012)
Prevention of recurrence
DVT/PE
√
(2014)
√
(2012)
√
(2014)
Edoxaban
(Savaysa®)
Pending
FDA
Approval