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ANTICOAGULATION ISSUES
In Geriatric Population
Ann McBride, M.D.
UW Anticoagulation Service
• No financial disclosures
• Underuse of Anticoagulation for Atrial
Fibrillation
– Balance of Stroke vs. Bleeding Risks
– Alternatives
• Warfarin Initiation and Maintenance
• Bridging Therapy
Seventh ACCP Conference on Antithrombotic
and Thrombolytic Therapy:
Evidence Based Guidelines
• CHEST Supplement, September 2004
• Overall CVA Risk for AF 4.5% per year
• Risk increases with Age
– 1.5% per year 50-59 yo
– 10% per year 80-89 yo
– 20% per year 90 yo
C
H
A
D
S2
Gage et al, Circulation 2004
Congestive Heart Failure
Hypertension
-Treated; untreated >140/90 mmHg
Age
-Older than 75
Diabetes
Stroke - 2
CHADS2
CVA risk/yr on ASA
Low = 0
0.8
Med = 1-2
2.7
High = 3 or more
5.3
• Adjusted dose warfarin—Target INR 2.5—
reduces CVA risk 60%
• ASA reduces CVA risk 20%
Warfarin Also Decreases Severity
• INR 2.0-3.0
• Associated with reduced severity of stroke
• Greater likelihood of survival
INR Intensity & CVA Severity
• 596 strokes/13,559 pts w/ NVAF
– 32% warfarin
– 27% ASA
– 42% neither
Hylek, et al, N Engl J Med 2003
1. Risk for CVA sharply increased INR < 2
2. CVA severity & fatality
with INR 1.5 – 1.9 ~ INR < 1.5
3. With INR 2-3, CVA more likely to be
“minor”
Bleeding Risk
• Warfarin increases risk of major
hemorrhage
1.7 x risk associated with ASA
Bleeding Risk
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65 yo and older
Hx of noncardioembolic CVA
Hx of GI Bleed
> 1 Comorbid Conditions
– Recent MI
– Hct less than 30
– Creatinine > 1.5
– Diabetes
Beyth et al. Am J Med 1998
250 Patients with AF or VTE
SCORE
Low = 0
MAJOR BLEED
Less than 3%
Moderate = 1-2
12%
High = 3
48%
(First 12 mos)
• Overall incidence of major bleed 6.5%
• Greatest risk for bleed first 30 days
• Most were avoidable maintaining
therapeutic INR range and avoiding
NSAIDs
Other Risk Factors
Excess Warfarin Anticoagulation
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APAP intake 9100 mg/wk or more
New medication known to increase warfarin effect
(Note: antibiotic, PPI, amiodarone, SSRI)
Bleed vs. CVA risk
Recent diarrheal illness
Decreased oral intake
Incorrectly taking higher dose of warfarin than
prescribed
Hylek et al. JAMA 1998
STROKE RISK
-CHF
vs. Bleeding Risk
Hx GI Bleed
-Hypertension
-75 yo & Older
65 yo & Older
-DM
-Stroke
Hx CVA
Comorbid > 1
Recent MI
Hct 30 or less
Cr > 1.5
DM
• 145 pts w/ ICH on warfarin
• 870 pts on warfarin w/o ICH
• Increasing Age (especially > 85)
• Increasing INR (especially > 3.5)
Fang et al. Annals of Internal Medicine 2004
• Risk of ICH was NOT lower in elderly pts
w/ AF when INR < 2.0 compared to INR
2.0-3.0
• EVEN FOR PTS OLDER THAN 75
ACCP Recommendations
No Risk Factors
0-1 risk factor
More than 1 risk factor
ASA 325 mg/day
Warfarin (INR=2.5) or
ASA 325 mg/day
Warfarin (INR = 2.5)
Atrial Flutter & Paroxysmal AF recommendations
same as for sustained NVAF
Bottom Line
• Stroke Risk
• Bleeding Risk
• Patient Functional & Cognitive Status
•
incl. falls risk
Patient Compliance
• Patient Preference
Suggest:
1. INR 2.5 (2.0 - 3.0)
2. Attention to risk factors for bleeding
If bleed occurs, target INR 2.2 (1.8 - 2.5)
3. More frequent monitoring
4. Attention to Rx med or OTC med change
•
Role of Anticoagulation Clinic
Patient Sample #1
Initiating Warfarin
Elderly
Frail
Malnourished
CHF
Liver Disease
Concurrent Medications
(cytochrome P450 isoenzymes mutation)
Lower Dose In Elderly
• “…starting dose of less than 5 mg might be
appropriate in the elderly…”
• Nomograms available, but few geriatric
patients represented
Daily Warfarin Dose
(in AF)
Age
Male
Female
50-59
5.4 mg
5.0 mg
60-69
4.6 mg
4.0 mg
70-79
4.3 mg
3.5 mg
80-89
3.9 mg
3.0 mg
> 90
3.6 mg
3.0 mg
Garcia et al, CHEST June 2005
• In each age group, median daily dose for
afib pts less than for VTE pts
• Older women require lowest doses
• When warfarin initiated, 5 mg/day will
lead to overanticoagulation for many
geriatric patients
• Lower initiation and maintenance doses for
elderly patients
Warfarin Initiation (hospitalized*)
• 4 mg daily x 3 days @ dinnertime
• INR – Morning 4th Day
• INR 1.0 to < 1.3
5 mg
1.3 to < 1.5
4 mg
1.5 to < 1.7
3 mg
1.7 to < 1.9
2 mg
1.9 to < 2.5
1 mg
> 2.5
daily INR hold until INR < 2.5
resume @ 1 mg/day
• Otherwise, INR repeated every 2-3 days
Siguret et al. Am J Med 2005;118:137-142
Other Options ???
• For NVAF pts – ACTIV Study
– Warfarin vs. ASA/Clopidigrel
• Ximelagatran
Ximelegatran
• Oral Direct Thrombin Inhibitor
• Fixed Dose
• Fast onset and offset activity
• Very few food/drug interactions
• No laboratory monitoring
Ximelegatran, cont.
•
Adverse Effects
1. Liver enzyme elevation
2. Risk for CAD
AstraZeneca EXANTA® (ximelagatran) Tablets NDA 21-686 FDA
Advisory Committee Briefing Document 10 September 2004 pg. 109
Bridging Therapy
Anticoagulation Perioperative
Interruption of Warfarin
VTE Risk vs. Hemorrhage Risk
Chest 2001, September Supplement
Cleveland Clinic Journal of Medicine, 2005;72(Suppl 1)
Chest 2004;126(3):September 2004 Supplement, pg. 215S