Practical Cardiovascular Review

1. Debbie L. Cardell, MD
Div Gen Med UTHSCSA 2/29/08
Anticoagulation
Debbie L. Cardell, MD
Asst. Clinical Prof of Medicine
Medical Director UHC-D Anticoagulation
Clinic

2. Debbie L. Cardell, MD
Div Gen Med UTHSCSA 2/29/08
Today’s Topics
• 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

3. Debbie L. Cardell, MD
Div Gen Med UTHSCSA 2/29/08
Diagnoses requiring warfarin
• Atrial fibrillation - sometimes
• Valvular Heart Disease
• Prosthetic heart valves
• DVT
• PE
• Hypercoagulable States - sometimes
• THR, TKA, hip fracture repair
• Pulmonary Hypertension

4. Debbie L. Cardell, MD
Div Gen Med UTHSCSA 2/29/08
Copyright ©2001 American Heart Association
Fuster, V. et al. Circulation 2001;104:2118-2150
Antithrombotic therapy for prevention of stroke (ischemic and hemorrhagic) in patients
with nonvalvular AF: adjusted-dose warfarin compared with placebo

5. Debbie L. Cardell, MD
Div Gen Med UTHSCSA 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

6. Debbie L. Cardell, MD
Div Gen Med UTHSCSA 2/29/08
Question 1
• Does the patient need anticoagulation?

7. Debbie L. Cardell, MD
Div Gen Med UTHSCSA 2/29/08
Answer
• No
• Provide proof for your answer

8. 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

9. Debbie L. Cardell, MD
Div Gen Med UTHSCSA 2/29/08
CHADS2 score and risk of stroke
Score Risk of Stroke per 100 patient
years
0 1.9
1 2.8
2 4.0
3 5.9
4 8.5
5 2.5
6 18.2

10. Debbie L. Cardell, MD
Div Gen Med UTHSCSA 2/29/08
Interpreting the CHADS2 score
Score Risk Anticoagula
tion
Therapy
Considerati
ons
0 Low Aspirin 325 mg
likely to
offer most
benefit
1-2 Moderate Aspirin or
Warfarin
INR goal 2-
3
3 High Warfarin INR goal 2-
3

11. 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.

12. 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%

13. Debbie L. Cardell, MD
Div Gen Med UTHSCSA 2/29/08
Question 2
• Does this patient need warfarin?

14. Debbie L. Cardell, MD
Div Gen Med UTHSCSA 2/29/08
Interpreting the CHADS2 score
Score Risk Anticoag-
ulation
Therapy
Considera-
tions
0 Low Aspirin 325 mg
likely to
offer most
benefit
1-2 Moderate Aspirin or
Warfarin
INR goal
2-3
3 High Warfarin INR goal
2-3

15. 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

16. 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?

17. 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

18. Debbie L. Cardell, MD
Div Gen Med UTHSCSA 2/29/08
Valvular Disease
• MVP with h/o stroke or embolization – ASA 50-
160 mg
• MVP with ASA failure – warfarin – long-term
range 2-3
• Rheumatic heart disease – mitral valve – with a-
fib 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

19. 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?

20. 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)

21. 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

22. 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?

23. Debbie L. Cardell, MD
Div Gen Med UTHSCSA 2/29/08
Answer
• Yes

24. 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

25. 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

26. Debbie L. Cardell, MD
Div Gen Med UTHSCSA 2/29/08
Question 6
• What is her INR goal?
• How long would you treat her?

27. 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

28. Debbie L. Cardell, MD
Div Gen Med UTHSCSA 2/29/08
Classifying Patients
• First-episode DVT secondary to a transient risk
factor
• First-episode DVT and concurrent cancer
• First-episode idiopathic DVT
• First-episode DVT associated with a
prothrombotic genotype
• Recurrent DVT
CHEST 2003

29. 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

30. 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?

31. Debbie L. Cardell, MD
Div Gen Med UTHSCSA 2/29/08
DVT in the setting of Cancer
• LMWH is recommended the in CHEST guidelines
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

32. 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

33. Debbie L. Cardell, MD
Div Gen Med UTHSCSA 2/29/08
Question 7
• What is his INR goal?
• How long do you treat him?

34. 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. 2.0-
3.0. 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).

35. 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)

36. 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?

37. 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

38. 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

39. 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

40. Debbie L. Cardell, MD
Div Gen Med UTHSCSA 2/29/08
When not to screen
• 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

41. 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.

42. 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

43. 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

44. 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
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?

45. 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

46. 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

47. 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

48. Debbie L. Cardell, MD
Div Gen Med UTHSCSA 2/29/08
Hip Fracture Surgery
• Same recommendations as Total Hip
Replacement

49. 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

50. 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%

51. 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%?

52. 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

53. 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

54. 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

55. Debbie L. Cardell, MD
Div Gen Med UTHSCSA 2/29/08
Kovacs, M. J. et. al. Ann Intern Med 2003;138:714-719
5-mg Warfarin Initiation Nomogram

56. 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

57. 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?

58. 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

59. 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?

60. 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

61. 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

62. 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?

63. 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

64. 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.

65. 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

66. Debbie L. Cardell, MD
Div Gen Med UTHSCSA 2/29/08
Common Bad Actors
• Acetataminophen
• Trimethoprim/sulfamethoxazole
• Fluoroquinolones
• Antibiotics in general
• Gemfibrozil
• Aspirin
• Clopidogrel
• Prednisone

67. 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

68. 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

69. 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

70. Debbie L. Cardell, MD
Div Gen Med UTHSCSA 2/29/08

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Div Gen Med UTHSCSA 2/29/08

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Div Gen Med UTHSCSA 2/29/08

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Div Gen Med UTHSCSA 2/29/08

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Div Gen Med UTHSCSA 2/29/08

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Div Gen Med UTHSCSA 2/29/08

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Div Gen Med UTHSCSA 2/29/08

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Div Gen Med UTHSCSA 2/29/08

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Div Gen Med UTHSCSA 2/29/08

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Div Gen Med UTHSCSA 2/29/08

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Div Gen Med UTHSCSA 2/29/08

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Div Gen Med UTHSCSA 2/29/08

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Div Gen Med UTHSCSA 2/29/08

83. 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

84. 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

85. Debbie L. Cardell, MD
Div Gen Med UTHSCSA 2/29/08
Questions