Transcript Anticoagulation - University Health System

Anticoagulation
Debbie L. Cardell, MD
Asst. Clinical Prof of Medicine
Medical Director UHC-D Anticoagulation
Clinic
Debbie L. Cardell, MD
Div Gen Med UTHSCSA
2/29/08
Today’s Topics
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Diagnoses for which anticoagulation is necessary
Duration of therapy
INR goal
Starting warfarin
Sources of evidenced based medicine
Drug/Drug interactions
System wide protocol
Work up of PE/DVT
Debbie L. Cardell, MD
Div Gen Med UTHSCSA
2/29/08
Diagnoses requiring warfarin
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Atrial fibrillation - sometimes
Valvular Heart Disease
Prosthetic heart valves
DVT
PE
Hypercoagulable States - sometimes
THR, TKA, hip fracture repair
Pulmonary Hypertension
Debbie L. Cardell, MD
Div Gen Med UTHSCSA
2/29/08
Antithrombotic therapy for prevention of stroke (ischemic and hemorrhagic) in patients
with nonvalvular AF: adjusted-dose warfarin compared with placebo
Fuster, V. et al. Circulation 2001;104:2118-2150
Debbie L. Cardell, MD
Div Gen Med UTHSCSA
Copyright ©2001 American Heart Association
2/29/08
Case 1
• 46 y.o. male continuity patient with
allergic rhinitis, found on exam to have
irregular pulse. No other medical
problems.
• Pulse irreg. 76 bpm, BP 132/76
• EKG shows a-fib
Debbie L. Cardell, MD
Div Gen Med UTHSCSA
2/29/08
Question 1
• Does the patient need anticoagulation?
Debbie L. Cardell, MD
Div Gen Med UTHSCSA
2/29/08
Answer
• No
• Provide proof for your answer
Debbie L. Cardell, MD
Div Gen Med UTHSCSA
2/29/08
Atrial Fibrillation
• CHADS2 score is an easy to use clinical
tool for determining who needs warfarin
• C – CHF- 1 point
• H – treated HTN - 1 point
• A – age >75 – 1 point
• D – diabetes – 1 point
• S – prior history of stroke or TIA-2 points
Debbie L. Cardell, MD
Div Gen Med UTHSCSA
2/29/08
CHADS2 score and risk of stroke
Score
0
1
2
3
4
5
6MD
Debbie L. Cardell,
Div Gen Med UTHSCSA
Risk of Stroke per 100 patient
years
1.9
2.8
4.0
5.9
8.5
2.5
18.2
2/29/08
Interpreting the CHADS2 score
Score
Risk
Anticoagula Considerati
tion
ons
Therapy
0
Low
Aspirin
325 mg
likely to
offer most
benefit
Moderate
Aspirin or
Warfarin
INR goal 23
High
Warfarin
INR goal 23
1-2
3
Debbie L. Cardell, MD
Div Gen Med UTHSCSA
2/29/08
Exception to CHADS2
• Although a patient with a prior stroke and
no other risk factors would only have a
score of 2 and calculates out as a
moderate risk, they are truly high risk and
should be treated with warfarin in the
absence of contraindications.
Debbie L. Cardell, MD
Div Gen Med UTHSCSA
2/29/08
Case 2
• 54 y.o. man with HTN well controlled on
HCTZ and metoprolol, found to have
irregular pulse
• EKG shows a-fib
• Echo one year ago EF 60%
Debbie L. Cardell, MD
Div Gen Med UTHSCSA
2/29/08
Question 2
• Does this patient need warfarin?
Debbie L. Cardell, MD
Div Gen Med UTHSCSA
2/29/08
Interpreting the CHADS2 score
Score
Risk
Anticoagulation
Therapy
Considerations
0
Low
Aspirin
325 mg
likely to
offer most
benefit
Moderate
Aspirin or
Warfarin
High
Warfarin
INR goal
2-3
INR goal
2-3
1-2
3
Debbie L. Cardell, MD
Div Gen Med UTHSCSA
2/29/08
Valid contraindications to warfarin
• Patient refusal
• Non-compliance with INR monitoring
• Alcohol consumption
• Bleeding diathesis
• History of major bleeding
Debbie L. Cardell, MD
Div Gen Med UTHSCSA
2/29/08
Question 3
• 56 y.o. woman with MVP admitted 4 mos
ago for TIA
• Does she need warfarin?
Debbie L. Cardell, MD
Div Gen Med UTHSCSA
2/29/08
Answer
• Only if she is an ASA failure
• MVP with h/o stroke or TIA –ASA dose of
50-160mg daily
• If fails ASA – then warfarin
Debbie L. Cardell, MD
Div Gen Med UTHSCSA
2/29/08
Valvular Disease
• MVP with h/o stroke or embolization – ASA 50•
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160 mg
MVP with ASA failure – warfarin – long-term
range 2-3
Rheumatic heart disease – mitral valve – with afib and/or prior history of stroke – lifetime use of
warfarin with a goal of 2-3
Rheumatic Mitral Valve disease and NSR with
Left Atrial size >5.5 cm – lifetime warfarin goal
2-3
Debbie L. Cardell, MD
Div Gen Med UTHSCSA
2/29/08
Question 4
• 60 y.o. man with prosthetic aortic valve,
echo shows nl EF. He has never had a
stroke or TIA. He has a bi-leaflet valve.
• What is his INR goal?
Debbie L. Cardell, MD
Div Gen Med UTHSCSA
2/29/08
Prosthetic Heart Valves
• Goals
– Aortic position – NSR, NL LA size, bi-leaflet or tilting
disc prosthesis - INR 2.0-3.0
– Aortic position – other risk factors* INR 2.5-3.5
– Mitral position – 2.5-3.5
• Duration – lifetime if mechanical, 12 weeks post
surgery if bio-prosthetic (porcine)
Debbie L. Cardell, MD
Div Gen Med UTHSCSA
2/29/08
AVR + Other Risk Factors = INR
2.5-3.5
• Atrial Fibrillation
• Myocardial infarction
• Left atrial enlargement > 5.5cm
• Endocardial damage
• Low ejection fraction
• Caged ball or caged disc valve
Debbie L. Cardell, MD
Div Gen Med UTHSCSA
2/29/08
Question 5
• Patient with AVR tells you his brother just
had an MI at 49y.o. He picked up a new
habit, smoking, since you last saw him.
• Would you start ASA for primary
prevention of CV disease?
Debbie L. Cardell, MD
Div Gen Med UTHSCSA
2/29/08
Answer
• Yes
Debbie L. Cardell, MD
Div Gen Med UTHSCSA
2/29/08
Aspirin Plus Warfarin?
• When?
• Only proven benefit is in patients with
Prosthetic Valves and increased CV risk or
previous MI
– WARIS II
– ASPECT 2
• Dose should be 81mg
Debbie L. Cardell, MD
Div Gen Med UTHSCSA
2/29/08
Next Case
• 28 y.o. woman presents to the ER on one
of your call days with a unilateral swollen
leg
• Doppler reveal a DVT
• History reveals she just had breast
reduction surgery 2 weeks ago
Debbie L. Cardell, MD
Div Gen Med UTHSCSA
2/29/08
Question 6
• What is her INR goal?
• How long would you treat her?
Debbie L. Cardell, MD
Div Gen Med UTHSCSA
2/29/08
Deep Vein Thrombosis
• INR goal is 2.0-3.0
• Duration depends on clinical scenario
Debbie L. Cardell, MD
Div Gen Med UTHSCSA
2/29/08
Classifying Patients
• First-episode DVT secondary to a transient risk
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factor
First-episode DVT and concurrent cancer
First-episode idiopathic DVT
First-episode DVT associated with a
prothrombotic genotype
Recurrent DVT
CHEST 2003
Debbie L. Cardell, MD
Div Gen Med UTHSCSA
2/29/08
1st DVT, Transient Risk Factor
• Treat to INR 2-3 for 3 months
• Transient Risk factors include
– Surgery
– Pregnancy
– Hospitalization
– Trauma
– Fracture
Debbie L. Cardell, MD
Div Gen Med UTHSCSA
2/29/08
Next Case
• 67 y.o. male continuity patient seeing you
after hospital discharge, comes to clinic
for follow up. He was admitted for a UE
DVT. During admission he was found to
have widely metastatic liver cancer.
• What is your anticoagulant of choice?
• How long do you treat him?
Debbie L. Cardell, MD
Div Gen Med UTHSCSA
2/29/08
DVT in the setting of Cancer
• LMWH is recommended the in CHEST guidelines
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for the first 3-6 months of long term therapy
LMWH is recommended for advanced and
metastatic cancers
LMWH is recommended during chemotherapy
In select patients with localized disease, warfarin
can be considered
Debbie L. Cardell, MD
Div Gen Med UTHSCSA
2/29/08
Next Case
• 37 y.o. man in your clinic comes in acutely
complaining of leg pain and swelling.
• He denies, travel, recent surgery,
hospitalization, prolonged immobilization.
• You are able to obtain dopplers.
• He has a DVT
Debbie L. Cardell, MD
Div Gen Med UTHSCSA
2/29/08
Question 7
• What is his INR goal?
• How long do you treat him?
Debbie L. Cardell, MD
Div Gen Med UTHSCSA
2/29/08
First Idiopathic VTE
• At least 6 months (6-12 months)
– PREVENT trial – after 3 months of anticoagulation,
508 patients randomized to continuation of warfarin
(INR 1.5-2.0) vs. placebo. Trial stopped after 4.3
years when there was a significantly lower rate of
recurrent VTE in the warfarin group (2.6 versus 7.2
per 100 patient-years, hazard ratio [HR] 0.36, 95% CI
0.19-0.67)
– ELATE – after 3 months of INR 2.0-3.0, 738 patients
randomized low dose warfarin INR 1.5-1.9 vs. 2.03.0. f/u 2.4 yrs. Recurrent VTE was significantly
lower in the higher dose warfarin group (1.9 versus
0.7 per 100 patient-years, HR 2.8, 95% CI 1.1-7.0).
Debbie L. Cardell, MD
Div Gen Med UTHSCSA
2/29/08
After six months
• Risks and benefits need to be reviewed with the
patient
– Risk of minor bleeding with continued anticoagulation
12.8 per 100 pt years, major bleeding is 2.7 per 100
patient-years, with a case fatality rate of 9.1 percent
(95% CI 2.5-22) Ann Intern Med 2003 Dec 2;139(11):893-900.
– Risk of recurrent VTE on no warfarin 7.2-8.4 per 100
pt years in PREVENT and THRIVE III trials, low dose
warfarin 1.9-2.6 per 100 pt years (ELATE and
PREVENT), and .7 episodes per 100 pt years on full
dose warfarin (ELATE)
Debbie L. Cardell, MD
Div Gen Med UTHSCSA
2/29/08
Case Continued
• His 6 months of warfarin therapy are over
• You discuss the risks and benefits of
treating him for a year vs. stopping now
• He opts to stop the warfarin
• Should you test him for acquired and
hereditary thrombophilias?
• Are there any other tests to determine his
individual risk?
Debbie L. Cardell, MD
Div Gen Med UTHSCSA
2/29/08
Screening for Thrombophilias
• Controversial – there is no consensus
• Arguments against screening –
– excessive, not cost effective, does not impact
treatment
• Arguments for screening –
– some patients (1-2%) have very high risk profiles,
knowledge could help manage risky situations such as
surgery and pregnancy
– Helps in screening of family members
Debbie L. Cardell, MD
Div Gen Med UTHSCSA
2/29/08
Inherited Thrombophilias
• Require life long anticoagulation only in the following
cases:
– Two or more spontaneous thromboses or one spontaneous
thrombosis in the case of antithrombin deficiency or the
antiphospholipid syndrome
– One spontaneous life-threatening thrombosis (e.g., near-fatal
pulmonary embolism; cerebral, mesenteric, or portal vein
thrombosis)
– One spontaneous thrombosis at an unusual site (e.g., mesenteric
or cerebral vein)
– One spontaneous thrombosis in the presence of more than a
single genetic defect predisposing to a thromboembolic event
UpToDate
Debbie L. Cardell, MD
Div Gen Med UTHSCSA
2/29/08
Consider screening
• In Strongly Thrombophilic patients –
– First idiopathic VTE prior to 50 y.o.
– History of recurrent thrombotic episodes
– First-degree relative with thrombotic episode
prior to the age of 50
Debbie L. Cardell, MD
Div Gen Med UTHSCSA
2/29/08
When not to screen
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Recent major surgery, trauma, or immobilization
Active malignancy
Systemic lupus erythematosus
Inflammatory bowel disease
Myeloproliferative disorders
Heparin-induced thrombocytopenia with
thrombosis
Preeclampsia at term
Retinal vein thrombosis
Debbie L. Cardell, MD
Div Gen Med UTHSCSA
2/29/08
Individual Risk Assessment
• D-dimer testing – 4 studies have shown an
increased risk of recurrent VTE in patients
with elevated D-dimers after 3 months of
anticoagulation HR 2-2.5
– One of the studies showed only 5 patients out
of 186 with a normal D-dimer with a recurrent
VTE, this give a negative predictive value of
>96%.
Thromb Haemost 2002 Jan;87(1):7-12.
Debbie L. Cardell, MD
Div Gen Med UTHSCSA
2/29/08
Recurrent VTE
• Trials are ongoing to determine the
optimal duration of treatment, but for now
recommendations say “indefinite” unless
there is a reversible cause
• If reversible cause – then treat until the
risk factor is no longer an issue
Debbie L. Cardell, MD
Div Gen Med UTHSCSA
2/29/08
Upper Extremity Thrombosis
• General consensus is that this represents a
more thrombogenic patient
• No randomized controlled trials to
determine the most appropriate length of
therapy
• If a reversible cause – can treat for 3-6
months
• If not – long term anticoagulation
Debbie L. Cardell, MD
Div Gen Med UTHSCSA
2/29/08
Next Case
• You are called to the ER to see one of your clinic
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patients. She is 42 y.o. c/o SOB for 1 day, she is
breathing rapidly and is tachycardic, her O2 sats
are 88%. CXR is negative. WBCs are normal.
She is not hypotensive.
You order a PE protocol CT. It is positive.
How long will this patient need to be treated for
her PE?
Debbie L. Cardell, MD
Div Gen Med UTHSCSA
2/29/08
Treatment for PE
• Treatment goals are the same as DVT
• Duration the same as DVT
• Exception is “massive PE” which is defined
as “shock” or requiring pressors – this
would constitute a reason for lifelong
anticoagulation
Debbie L. Cardell, MD
Div Gen Med UTHSCSA
2/29/08
Other Considerations
• Compression Stockings should be prescribed at
30-40mm Hg at the ankle in all patients with
DVT within a month after Dx and continued for
1-2 years. This has been proven to reduce the
incidence of post-thrombotic syndrome by 50%
Lancet 1997;349,759-762
• Patients should be on “ambulation as tolerated”
• NSAIDs are not recommended during the acute
treatment of DVT
Debbie L. Cardell, MD
Div Gen Med UTHSCSA
2/29/08
Total Hip Replacement
• Low Molecular Weight Heparin (LMWH)
or
• Warfarin with a target INR of 2.0-3.0
or
• Fondaparinux 2.5 mg daily
• Duration: 28-35 days
Debbie L. Cardell, MD
Div Gen Med UTHSCSA
2/29/08
Hip Fracture Surgery
• Same recommendations as Total Hip
Replacement
Debbie L. Cardell, MD
Div Gen Med UTHSCSA
2/29/08
Total Knee Arthroplasty (TKA)
• LMWH at high risk doses
or
• Warfarin with INR goal 2.0-3.0
or
• Fondaparinux
• Duration: 10 days
Debbie L. Cardell, MD
Div Gen Med UTHSCSA
2/29/08
Next Case
• 62 y.o. female with Pulmonary
Hypertension secondary to COPD
• She is in NSR
• Her last echo showed an EF of 50%
Debbie L. Cardell, MD
Div Gen Med UTHSCSA
2/29/08
Question 8
• Does she need warfarin?
• Does your recommendation change if her
EF was 20%?
Debbie L. Cardell, MD
Div Gen Med UTHSCSA
2/29/08
Pulmonary Hypertension
• INR goal of 2.0 for
– Pulmonary Hypertension secondary to chronic
thromboembolic disease
– PulmHTN with afib
– Idiopathic Pulmonary Hypertension
– Familial Pulmonary Hypertension
– Pulmonary Hypertension with severe left heart
failure
Debbie L. Cardell, MD
Div Gen Med UTHSCSA
2/29/08
Starting Dose
• Start with 5mg of warfarin (CHEST)
• Consider a lower dose in very elderly
• Get a baseline INR
• Follow a nomogram
Debbie L. Cardell, MD
Div Gen Med UTHSCSA
2/29/08
Nomogram
• One can be found in the Annals
– Annals of Internal Medicine 2003;138:714
Debbie L. Cardell, MD
Div Gen Med UTHSCSA
2/29/08
5-mg Warfarin Initiation Nomogram
Kovacs, M. J. et. al. Ann Intern Med 2003;138:714-719
Debbie L. Cardell, MD
Div Gen Med UTHSCSA
2/29/08
Initiation Case
• Your previous DVT patient is started on
5mg warfarin (following CHEST guidelines)
• His baseline INR is 1.1
• You start him on 1mg/kg of enoxaparin
BID
• He comes back on day three with an INR
of 1.4
Debbie L. Cardell, MD
Div Gen Med UTHSCSA
2/29/08
Question 9
• What dose do you tell him to take?
• When do you tell him to come back?
Debbie L. Cardell, MD
Div Gen Med UTHSCSA
2/29/08
Follow up
• Arrange for appointments as per the
nomogram
• INR check on days 3,4,5,6,
• Then twice weekly for two weeks
• Weekly for two more weeks
• If stable, then every 4 weeks
Debbie L. Cardell, MD
Div Gen Med UTHSCSA
2/29/08
Initiation of anticoagulation
• How many days of enoxaparin should you
write for?
• What are the instructions for stopping the
enoxaparin?
Debbie L. Cardell, MD
Div Gen Med UTHSCSA
2/29/08
Answer
• Write for a minimum of five days of
enoxaparin
• INR should be therapeutic for two days in
a row before stopping enoxaparin
Debbie L. Cardell, MD
Div Gen Med UTHSCSA
2/29/08
Monitoring
• After the initial 2 weeks, INRs usually
become more stable
• Maintenance nomograms may be utilized
to help in decision making
• An experienced clinician is equivalent to a
nomogram
Debbie L. Cardell, MD
Div Gen Med UTHSCSA
2/29/08
Maintenance Case
• 65 y.o. woman with A-fib, DM and
hyperlipidemia had to switch her statin
from atorvastatin to simvastatin for
insurance coverage purposes.
• Her repeat INR after med change shows
the INR is 3.6
• What adjustment do you make?
• When should she follow up?
Debbie L. Cardell, MD
Div Gen Med UTHSCSA
2/29/08
INR changes while on maintenance
• Worsening CHF
• New medication
• Stopped a medication
• Stopped or started smoking
• Increased or decreased physical activity
• Infection
This is why an experienced clinician performs as well as a nomogram or
calculator
Debbie L. Cardell, MD
Div Gen Med UTHSCSA
2/29/08
Anticoagulation Clinic vs. PCP
• Anticoagulation Clinic saves money
• Decreases hospitalizations (related to
anticoagulation)
• Decreases INRs outside of range
• Decreases anticoagulation related
complications
• Am J Hosp Pharm 985:42,304-308, Pharmacotherapy
10=995:15,732-739, Drug Intell Clin Pharm 1985;19,575-580, Arch
Intern Med 1998:158,1641-1647, Chest 2005:127,1515-1522.
Debbie L. Cardell, MD
Div Gen Med UTHSCSA
2/29/08
Drug Interactions
• Safest to assume all drugs interact with
warfarin
• Check all new medications in epocrates or
a similar program
• Don’t forget about herbals and over the
counter meds
Debbie L. Cardell, MD
Div Gen Med UTHSCSA
2/29/08
Common Bad Actors
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Acetataminophen
Trimethoprim/sulfamethoxazole
Fluoroquinolones
Antibiotics in general
Gemfibrozil
Aspirin
Clopidogrel
Prednisone
Debbie L. Cardell, MD
Div Gen Med UTHSCSA
2/29/08
When Forced
• If you must use one of these medications,
recheck the INR in 3 days
• OR look on MicroMedex and see how
strong the interaction is
• For Bactrim, decrease weekly warfarin
dose by 30% and recheck in 3 days
Debbie L. Cardell, MD
Div Gen Med UTHSCSA
2/29/08
System Based Protocol Goals
• Uniformity of treatment
• Encourage the use of evidence based
guidelines
• Create a patient registry
• Uniformity of dose adjustment and follow
up
• Provide seamless care
Debbie L. Cardell, MD
Div Gen Med UTHSCSA
2/29/08
Resources
• CHADS2 score
• Wells score for DVT and PE
• Warfarin initiation nomogram
• Warfarin maintenance calculator
• CHEST guidelines
• Patient information in English and Spanish
Debbie L. Cardell, MD
Div Gen Med UTHSCSA
2/29/08
Debbie L. Cardell, MD
Div Gen Med UTHSCSA
2/29/08
Debbie L. Cardell, MD
Div Gen Med UTHSCSA
2/29/08
Debbie L. Cardell, MD
Div Gen Med UTHSCSA
2/29/08
Debbie L. Cardell, MD
Div Gen Med UTHSCSA
2/29/08
Debbie L. Cardell, MD
Div Gen Med UTHSCSA
2/29/08
Debbie L. Cardell, MD
Div Gen Med UTHSCSA
2/29/08
Debbie L. Cardell, MD
Div Gen Med UTHSCSA
2/29/08
Debbie L. Cardell, MD
Div Gen Med UTHSCSA
2/29/08
Debbie L. Cardell, MD
Div Gen Med UTHSCSA
2/29/08
Debbie L. Cardell, MD
Div Gen Med UTHSCSA
2/29/08
Debbie L. Cardell, MD
Div Gen Med UTHSCSA
2/29/08
Debbie L. Cardell, MD
Div Gen Med UTHSCSA
2/29/08
Debbie L. Cardell, MD
Div Gen Med UTHSCSA
2/29/08
Referring Patients
• From inpatient setting – use Consult upon
discharge option
• Anticoagulation referral
• Tell patient to go to ExpressMed at the
hospital in 2-3 days (follow protocol)
• Order INR in Sunrise
– Stat patient waiting
– Give paper to patient
Debbie L. Cardell, MD
Div Gen Med UTHSCSA
2/29/08
Referring Patients
• From Outpatient setting
– Use Outpatient Consult or Anticoagulation
Consult
– In pull down menu, select anticoagulation
– Tell patient to go to ExpressMed clinic in 2-3
days (follow protocol)
– Order INR from within Sunrise
• Stat patient waiting
• Hand the paper to the patient
Debbie L. Cardell, MD
Div Gen Med UTHSCSA
2/29/08
Questions
Debbie L. Cardell, MD
Div Gen Med UTHSCSA
2/29/08