Transcript Stroke Prevention in AF

Primary Care Education Progam
Steering Committee
FAMILY PRACTITIONERS:
Dr. Carl Fournier, Montreal, QC
Dr. Peter Lin, Toronto, ON
Dr. Vinod Patel, St. John’s, NFLD
Dr. Kevin Saunders, Winnipeg, MB
Dr. Richard Ward, Calgary, AB
SPECIALISTS:
Dr. Paul Dorian, Toronto, ON
Dr. Victor Huckell, Vancouver, BC
Dr. Mukul Sharma, Ottawa, ON
Dr. Jeffrey Weitz, Hamilton, ON
Incidence of AF: Expected to Increase as
Population Ages
Projected Number of Persons With
AF in the US: 2000- 2050
Millions
Age- and Sex-Adjusted
Incidence of AF in 1995-2000
Year
Circulation 2006;114:119
Perspectives on Stroke
• About 80% of all strokes are ischemic1
• Effect of first ischemic stroke in patients with AF:
60% are disabling, 20% are fatal2
• ICH has a 30-day mortality rate of 35% to 52%3
• Severe strokes are viewed by many patients as
equal to or worse than death4,5
1Heart
and Stroke Foundation; 2 Gladstone Stroke 2009;40:235; 3AHA Stroke 1999;30:905-15; 4Gage
Arch Intern Med 1996;156:1829; 5Solomon Stroke 1994;25:1721
Embolic Stroke
• Noncontrast CT brain scan
showing two discrete areas of
infarction (arrows) within the right
middle cerebral artery
Kelley RE & Minagar A. Southern Medical Journal 2003;96(4):343-349
Stroke Severity in Patients with AF
Effect of first ischemic stroke in patients with AF (n=597)
60%
% of patients
50%
40%
30%
20%
10%
0%
AF=atrial fibrillation
Disabling
Fatal
Gladstone DJ et al. Stroke 2009; 40:235-240
Warfarin in Atrial Fibrillation:
• Warfarin reduces stroke in non-valvular AF by
64%
- Significant increase in intracranial and other hemorrhage
• Registries show 50-60% of eligible patients
receive warfarin
• In clinical trials, time in therapeutic range (TTR)
is 60-68%
• In general practice, TTR is typically <50%
1Hart
Ann Int Med 2007;146:857; 2Hylek Stroke 2006;37:1075; 3Singer Chest 2008;13;3:546S
4Gladstone
Stroke 2009;40:235; 5Matchar Am J Med 2002;113:42; 6Bungard Pharmacotherapy 2000;20:1060
CCS 2012 Update to AF Guidelines
Assess Thromboembolic Risk (CHADS2)
CHADS2 = 0
CHADS2 = 1
CHADS2 ≥ 2
Increasing stroke risk
No antithrombotic
No
additional
risk factors
for stroke
ASA
Either
female
sex or
vascular
disease
OAC*
Age ≥ 65 yrs
or combination
of female sex
and vascular
disease
OAC = Oral anticoagulant
ASA = Aspirin
1. Skanes AC, et al. Can J Cardiol 2012;28:125-136.
OAC*
*Aspirin is a reasonable
alternative in some as
indicated by risk/benefit
OAC
Consider stroke risk vs. bleeding risk
Only when the stroke risk is low and
bleeding risk is high does the risk/benefit
ratio favour no antithrombotic therapy
CCS 2012 Update to AF Guidelines
When oral anticoagulant therapy is indicated, most patients
should receive dabigatran, rivaroxaban, or apixaban*, in
preference to warfarin
• Dabigatran and apixaban have greater efficacy and rivaroxaban has similar
efficacy for stroke prevention
• Dabigatran and rivaroxaban have no more major bleeding and apixaban has
less
• All three new oral anticoagulants have less intracranial hemorrhage and are
much simpler to use
*Not yet approved in Canada
1. Skanes AC, et al. Can J Cardiol 2012;28:125-136.
Prevention of Stroke
Cross-trial comparisons must be interpreted with caution due to differing methodologies and patient
populations.
Superiority
p-value
Stroke or Systemic Embolism
Dabigatran 110 mg BID
Dabigatran 150 mg BID
0.90
0.29
0.65
Rivaroxaban 20 mg QD
Apixaban 5 mg BID
0.88
Dabigatran 150 mg BID
0.01
1.11
0.35
0.76
0.03
0.94
Rivaroxaban 20 mg QD
0.59
0.92
Apixaban 5 mg BID
0.50
0.12
0.79
Ischemic Stroke
Dabigatran 110 mg BID
<0.001
0.75
1.00
0.42
1.25
HR (95% CI)
Comparator better
1.50
Warfarin better
Connolly N Engl J Med 2010;363:1876; Patel N Engl J Med 2011;365:883; Granger N Engl J Med 2011;365:981
Boehringer Ingelheim (Canada) Ltd. cannot recommend the use of products outside the Canadian approved Product Monograph.
Reducing the Bleeding Risk
Cross-trial comparisons must be interpreted with caution due to differing methodologies and patient
populations.
Intracranial Hemorrhage
Dabigatran 110 mg BID
Dabigatran 150 mg BID
Rivaroxaban 20 mg QD
Apixaban 5 mg BID
Superiority
p-value
0.30
<0.001
0.41
<0.001
0.67
0.02
0.42
ISTH Major Bleeding
Dabigatran 110 mg BID
<0.001
0.80
0.003
0.93
Dabigatran 150 mg BID
0.31
1.04
Rivaroxaban 20 mg QD
0.58
0.69
Apixaban 5 mg BID
0.25 0.50
<0.001
0.75 1.00 1.25
HR (95% CI)
Comparator better
Warfarin better
Boehringer Ingelheim (Canada) Ltd. cannot recommend the use of products outside the Canadian approved Product Monograph.
Connolly N Engl J Med 2010;363:1876; Patel N Engl J Med 2011;365:883; Granger N Engl J Med 2011;365:981
New OAC vs. warfarin in moderate CKD
(eGFR <50 ml/min)
Stroke or Systemic Embolism
RR (95% CI)
Dabigatran 110 mg BID
0.77 (0.51-1.18)
Dabigatran 150 mg BID
0.55 (0.40-0.81)
Rivaroxaban 15 mg QD
0.86 (0.63-1.17)
Apixaban 2.5/5 mg BID
0.79 (0.57-1.20)
0.50
0.75
1.00
1.25
1.50
HR (95% CI)
New Agent Better
Warfarin Better
Hart RG, et al. Nat Rev Nephrol 2012 (on line)
Connolly SJ, et al. N Engl J Med. 2009; 361:1139
Fox KAA et al. Euro Heart J 2011; 32: 2387
Granger C, et al. N Engl J Med. 2011; 365: 981
New OAC vs. warfarin in moderate CKD
(eGFR <50 ml/min)
Major bleeding
RR (95% CI)
Dabigatran 110 mg BID
0.99 (0.76-1.28)
Dabigatran 150 mg BID
1.03 (0.80-1.34)
Rivaroxaban 15 mg QD
0.95 (0.72-1.26)
Apixaban 2.5/5 mg BID
0.50 (0.38-0.66)
0.50
0.75
1.00
1.25
1.50
HR (95% CI)
New Agent Better
Warfarin Better
Hart RG, et al. Nat Rev Nephrol 2012 (on line)
Connolly SJ, et al. N Engl J Med. 2009; 361:1139
Fox KAA et al. Euro Heart J 2011; 32: 2387
Granger C, et al. N Engl J Med. 2011; 365: 981
Safety Outcomes: RELY
D 110 mg vs. W
RR
95% CI
P
D 150 mg vs. W
RR
95% CI
P
D 110mg
Annual rate
D 150mg
Annual rate
W
Annual rate
Major or Minor
Bleeding
14.62%
16.42%
18.15%
0.78
0.73-0.83
<0.001
0.91
0.85-0.96
0.002
Intracranial
Bleeding
0.23 %
0.32 %
0.76 %
0.30
0.19-0.45
<0.001
0.41
0.28-0.60
<0.001
Major Bleeding
2.87 %
3.32 %
3.57%
0.80
0.70-0.93
0.003
0.93
0.81-1.07
0.32
Life-Threatening
Major Bleed
1.24 %
1.49 %
1.85 %
0.67
0.54-0.82
<0.001
0.80
0.66-0.98
0.03
Fatal Bleed*
0.19 %
0.23 %
0.33 %
0.58
0.35-0.97
0.039
0.70
0.43-1.14
0.15
GI Major Bleed
1.15 %
1.56 %
1.07 %
1.08
0.85-1.38
0.52
1.48
1.18-1.85
0.001
Connolly NEJM 2010;363:1876; *Eikelboom Circulation 2011;123:2363
Safety Outcomes*: ROCKET AF
Rivaroxaban
Warfarin
Event Rate (per
100
patient/years)
Event Rate (per
100
patient/years)
HR (95% CI)
P-value
Primary: Major and Non-Major
Clinically Relevant Bleeding
14.9
14.5
1.03 (0.96, 1.11)
0.44
Major:
3.6
3.4
1.04 (0.90, 1.20)
0.58
>2 g/dL Hgb drop
2.8
2.3
1.22 (1.03, 1.44)
0.02
Transfusion (> 2 units)
1.6
1.3
1.25 (1.01, 1.55)
0.04
Critical Bleeding
0.8
1.2
0.69 (0.53, 0.91)
0.007
Fatal Bleeding
0.2
0.5
0.50 (0.31, 0.79)
0.003
0.5
0.7
0.67 (0.47, 0.93)
0.02
3.2 % of pts
2.2% of pts
Not reported
<0.001
11.8
11.4
1.04 (0.96, 1.13)
0.35
10.1% of pts
8.6 % of pts
Not reported
<0.05
Intracranial Hemorrhage
Major GI Bleeding
Non-Major Clinically Relevant
Bleeding
Epistaxis
*Based on Safety On-Treatment Population
Patel N Engl J Med 2011;365:883
Bleeding and Net Clinical Outcomes:
ARISTOTLE
Apixaban
Warfarin
Event Rate (per
Event Rate
100
patient/years)
(per 100
patient/years)
Primary: Major
Bleeding
2.13
Intracranial
Hemorrhage
HR (95% CI)
Pvalue
3.09
0.69 (0.60, 0.80)
<0.001
0.33
0.80
0.42 (0.30, 0.58)
<0.001
Other Location
1.79
2.27
0.79 (0.68, 0.93)
0.004
Major GI Bleeding
0.76
0.86
0.89 (0.70, 1.15)
0.37
Major or Clinically
Relevant Non-Major
4.07
6.01
0.68 (0.61, 0.75)
<0.001
Net Clinical Outcome*
6.13
7.20
0.85 (0.78, 0.92)
<0.001
*Net Clinical Outcome: Stroke, systemic embolism, death, or major hemorrhage
Boehringer Ingelheim (Canada) Ltd. cannot recommend the use of products outside the Canadian approved Product Monograph.
Similarities Across the 3 Novel Oral Anticoagulants:
Comparing Dabigatran 150 mg, Rivaroxaban, and Apixaban
Vs. Warfarin
• All 3 agents were non-inferior to warfarin in
reducing the risk of stroke / systemic embolism
• All 3 agents reduced ICH
• The 3 agents seem to demonstrate a consistent
trend towards mortality reduction
Cross-trial comparisons must be interpreted with caution due to differing methodologies and patient
populations.
Connolly N Engl J Med 2010;363:1876; Patel N Engl J Med 2011;365:883; Granger N Engl J Med 2011;365:981
Boehringer Ingelheim (Canada) Ltd. cannot recommend the use of products outside the Canadian approved Product Monograph.
Differences:
Comparing Dabigatran 150 mg, Rivaroxaban, and Apixaban Vs. Warfarin
• Dabigatran and apixaban demonstrated
superiority over warfarin in reducing
stroke/systemic embolism
• Dabigatran reduced ischemic stroke
• Apixaban reduced major bleeding
• Rivaroxaban is dosed once daily
Cross-trial comparisons must be interpreted with caution due to differing methodologies and
patient populations.
Connolly N Engl J Med 2010;363:1876; Patel N Engl J Med 2011;365:883; Granger N Engl J Med 2011;365:981
Boehringer Ingelheim (Canada) Ltd. cannot recommend the use of products outside the Canadian approved Product Monograph.
Patients unsuitable for new anticoagulants
AF patients not recommended for therapy with new
anticoagulant agents approved for stroke prevention include:
• Patients with valvular heart disease
• Patients with mechanical valves
• Patients with advanced renal impairment (CrCl<30
mL/min)
• Patients with active bleeding
1. Pradax™ (Dabigatran Etexilate Capsules) Product Monograph, 2012, Boehringer Ingelheim Canada Ltd.
2. Xarelto™ (Rivaroxaban tablet) Product Monograph, February 2012, Bayer Inc.
Case: Patient with hypertension,
diabetes, prior TIA
Patient Profile:
Jack
Jack
• Jack is a 64-year old Caucasian man
• Married, lives with wife
• Works from home but frequently travels
to the US for work
• Goes to the gym twice/week
• He is 5’ 11” tall (180 cm)
• Weighs 187 lb (85 kg),
• BMI is 26.1
• “I’m here only because of my wife
… she thinks I had a stroke”
Medical History
• Jack’s medical conditions are as follows:
- Diagnosed with atrial fibrillation 3 years ago - on warfarin
- His INR has been stable although he admits this is difficult
because of his lifestyle and work-related activities
- Hypertension – on ramipril and thiazide
- Diabetes – on metformin
• Jack smokes 5-6 cigarettes/day, especially when he is
travelling
• Jack also drinks 1-2 glasses of wine or beer/day
- This increases to 2-3 glasses of wine or beer/day when he is
travelling (about once/month)
Medical History
• About 3 weeks ago Jack had a “spell”
-
While eating dinner he suddenly stopped speaking
The right side of his mouth drooped
The fork fell from his hand
It lasted 20 min
• Jack did not go the emergency department
- “I felt fine and was about to go on a trip”
• His INR one week ago was 1.5
Discussion Questions
1. What was the “spell”?
- Do you need any other clinical information
or investigations?
2. What are the options for
management?
Important Points
• The episode was focal, abrupt in onset and brief
- It meets the clinical diagnosis of TIA
- New criteria require the exclusion of tissue damage with brain
imaging
• The physical examination is directed toward excluding a
deficit which would suggest stroke
- Speech, motor function, facial strength, visual fields
- BP ( correlates with risk of hemorrhage)
• Investigations are directed toward exclusion of other
causes of TIA and excluding rare mimics
- CT head, carotid Doppler or CTA/MRA
1. Lindsay MP et al. Canadian Best Practice Recommendations for Stroke Care (Update 2010)
Canadian Stroke Network. www.hsf.sk.ca/siss/documents/2010
What-if Scenarios
• Jack wants to know when he can travel
- “They really need me in Peoria next week”
• What if his Doppler shows:
- < 50% carotid artery stenosis?
- 50-69% carotid artery stenosis?
• What if Jack’s CT report reads:
- Small area of hypodensity in the right centrum semiovale
consistent with infarction
Key Evidence
Most recent guidelines for stroke prevention in patients with AF
(CCS, 2012)
TIA / minor disabling ischemic stroke is associated with a high early
risk of recurrent stroke.
TIA is defined as a transient episode of neurologic dysfunction caused
by focal brain, spinal or retinal ischemia without infarction while
ischemic stroke is defined as an infarction [tissue injury] of central
nervous system tissue.
1. Skanes AC, et al. Can J Cardiol 2012;28:125-136.
2. Lindsay MP et al. Canadian Best Practice Recommendations for Stroke Care (Update 2010)
Canadian Stroke Network. www.hsf.sk.ca/siss/documents/2010
The Definition of Stroke/TIA
A clinical syndrome characterized by the
sudden onset of a focal neurological deficit
presumed to be on a vascular basis
1. Lindsay MP et al. Canadian Best Practice Recommendations for Stroke Care (Update 2010)
Canadian Stroke Network. www.hsf.sk.ca/siss/documents/2010
2. Johnston et al. Ann Neurol 2006; 60: 301–313.
Tissue Based TIA Definition
• Brief episode (typically <1h) caused by focal brain or retinal
ischemia without evidence of infarction
• Indicates risk
• Encourages neurodiagnostic tests
• Facilitates rapid intervention
Albers GW et al. N Engl J Med 2002;347:1713-1716.
Early risk of stroke after discharge from the
emergency department among patients with a
first-ever TIA
1. Gladstone D et al. CMAJ. 2004 Mar 30;170(7):1099-104.
Key Evidence
CHA2DS2- Vasc performed better when patients were categorized
as low [score = 0] moderate [score=1] or high [score = >2] risk
principally because of more precise estimates of thromboembolic risk
in patients with CHADS2 score of 0 or 1.
2 points for age >75 yrs and 1 point for age 65-74 yrs.
1 point each for vascular disease [prior MI, peripheral arterial disease
or aortic plaque] or female sex
1. Lip GY et al. Chest 2010;137:263-272.
2. Skanes AC, et al. Can J Cardiol 2012;28:125-136.
CHADS2 Score
(Simple prediction tool for assessing stroke risk)
• 1 point for Congestive Heart Failure
• 1 point for Hypertension
• 1 point for Age ≥ 75 years
• 1 point for Diabetes Mellitus
• 2 points for Prior Stroke or TIA
CHADS2 Score*
Stroke Rate, %/yr
(95 %CI)
0
1.9 (1.2 – 3.0)
1
2.8 (2.0 – 3.8)
2
4.0 (3.1 – 5.1)
3
5.9 (4.6 – 7.3)
4
8.5 (6.3 – 11.1)
5
12.5 (8.2 – 17.5)
6
18.2 (10.5 – 27.4)
*Score 0: Patients can be administered aspirin
*Score 1: Patients can be administered aspirin or anticoagulant
therapy
*Score ≥2: Patients should be administered anticoagulant therapy
1. Gage BF, et al. JAMA. 2001;285:2864-2870.
CHA2DS2-VASc Score
• 1 point for Congestive Heart Failure/
LV Dysfunction
• 1 point for Hypertension
CHA2DS2-VASc
Score*
One year event rate (95% CI) of hospital
admission and death due to
thromboembolism† per 100 person year
0
0.78 (0.78 – 1.04)
1
2.01 (1.70 – 2.36)
2
3.71 (3.36 – 4.09)
• 2 points for Prior Stroke or TIA1 or TE2
3
5.92 (5.53 – 6.34)
• 1 point for Vascular Disease3
4
9.27 (8.71 – 9.86)
5
15.26 (14.35 – 16.24)
• 1 point for Age 65-74 years
6
19.74 (18.21 – 21.41)
• 1 point for Sex category (female gender)
7
21.5 (18.75 – 24.64)
8
22.38 (16.29 – 30.76)
9
23.64 (10.62 – 52.61)
• 2 points for Age ≥ 75 years
• 1 point for Diabetes Mellitus
*Score 0: Patients can be administered aspirin
*Score 1: Patients can be administered aspirin or anticoagulant therapy
*Score ≥2: Patients should be administered anticoagulant therapy
†Includes peripheral artery embolism, ischemic stroke, and pulmonary embolism
1TIA
= Transient ischemic attack; 2TE = Thromboembolism
myocardial infarction, peripheral artery disease, aortic plaque
1. Lip GY et al. Chest 2010;137:263-272
3Prior
2. Olesen JB, et al. BMJ 2011;342:d124
3. Task Force or the Management of Atrial Fibrillation of the ESC. Eur Heart J
2010;31:236902429
What-if Scenarios
• What if this patient has experienced a TIA more recently,
e.g., this morning?
- What investigations should be conducted; what are any differences
between these investigations and those done if the TIA was
experienced 3 weeks ago?
- EKG, Blood work (including INR), renal function and lipid profile.
• Brain/neurovascular imaging to exclude a bleed or a large
infarct
Expert Recommendations
• Switch to a newer OAC if INR and eGFR are within
normal limits
• Antithrombotic therapy in CKD patients depends on
eGFR
- If eGFR >30 such patients should receive antithrombotic therapy
according to CHADS2 score as outlined in recommendation for
patients with normal renal function
Poor Prognosis in Warfarin-Associated
Intracranial Hemorrhage Despite
Anticoagulant Reversal
Dowlatshahi D, et al. Stroke 2012. DOI: 10.1161/STROKEAHA.112.652065
Background
• Anticoagulant-associated ICH (aaICH) presents with
large hematoma volumes, high risk of expansion, worse
outcomes than spontaneous hemorrhage
• Prothrombin complex connectrates (PCC) indicated for
urgent reversal of anticoagulation
Dowlatshahi D, et al. 2012. DOI: 10.1161/STROKEAHA.112.652065
CanPro Registry
• Determined outcomes in patients (N=141) with aaICH
treated with PCC
• Prospective inpatient registry of inpatients with aaICH
treated with Octaplex at stroke centres:
- Calgary, Edmonton, Ottawa
• Primary outcomes:
- INR correction
- Thrombotic events
- In-hospital mortality
Dowlatshahi D, et al. 2012. DOI: 10.1161/STROKEAHA.112.652065
Low Rate of Thrombotic Events
Thrombotic events associated with prothrombin complex concentrates (PCC) therapy
Time from PCC
infusion
Warfarin Indication
Ischemic stroke
21 days
Atrial fibrillation
Ischemic stroke
5 days
Atrial fibrillation
Ischemic stroke
1 day
Atrial fibrillation
Deep vein thrombosis
30 days
Atrial fibrillation
Deep vein thrombosis
21 days
Deep vein thrombosis
Myocardial infarction
28 days
Atrial fibrillation
Myocardial infarction
7 days
Pulmonary embolism
Thrombotic Event Type
• 30 day thrombotic event rate was 5%
• Only 3 events within 7d of therapy (2%)
Dowlatshahi D, et al. 2012. DOI: 10.1161/STROKEAHA.112.652065
Hematoma Growth
Significant hematoma growth despite INR
correction with PCC.
This patient was treated with 1000 U of
PCC and 10 mg vitamin K 98 minutes after
baseline CT scan.
Repeat INR was 1.3, 42 minutes after PCC
treatment and 1.2 the next day.
INR = international normalized ratio;
PCC = prothrombin complex concentrate
Dowlatshahi D, et al. 2012. DOI: 10.1161/STROKEAHA.112.652065
Poor Outcomes
Outcome by anticoagulant-associated ICH
Number
In-hospital
mortality*
Discharge mRS
(Median IQR)†
Intraparenchymal
71
30 (42.3%
5 (3)‡
Subdural
61
21 (34.4%
3 (4)§
Epidural
1
0
3
Subarachnoid
8
1 (12.5%)
3 (3)
Intracranial hemorrhage type
ICH = intracranial hemorrhage; mRS = modified Rankin Scale; IQR = interquartile range
*P = 0.3; †P=0.012; ‡mRS missing in 9; §mRS missing in 2
Dowlatshahi D, et al. 2012. DOI: 10.1161/STROKEAHA.112.652065
Conclusion
• Prothrombin complex concentrates (PCC) therapy rapidly
corrected INR in the majority of patients with
anticoagulant-associated ICH, yet mortality and morbidity
rates remained high
• Outcomes after anticoagulant-associated ICH can be
devastating even with a reversal strategy
Dowlatshahi D, et al. 2012. DOI: 10.1161/STROKEAHA.112.652065
Expected number of fatal hemorrhages,
intracranial hemorrhages, strokes and deaths
with different antithrombotic treatments
1. Eikelboom JW, et al. J Thromb Hemost 2012:10;966-968.
The potential role of antidotes
Agent
Half life
Antidote
Use
Heparins
1 hr
Protamine
CABG
LMWH
3-6 hrs
Protamine*
Rare
New OAC
6-18 hrs
Nil
??
Fonda
17-21 hrs
Nil
Rare
Warfarin
DAPT
20-60 hrs K, PCC, FFP
7-10 d
Platelets†
Common
Common
*Protamine (partial). †Platelets (partial for clopidogrel)
Management of Bleeding in
Patients Treated with Dabigatran
Mild bleeding
Delay next dose or
discontinue treatment as
appropriate
1. van Ryn J, et al. Thromb Haemostat 2010;103:1116-1127
2. Hankey GJ & Eikelboom JW. Circulation 2011;123:1436-1450
Management of Bleeding in
Patients Treated with Dabigatran
Moderate to severe
bleeding
• Stop dabigatran
• Monitor aPTT and TT
• Oral charcoal (if within 2 hr
of drug ingestion)
• Mechanical compression
• Fluid replacement and
hemodynamic support
• Blood product support
• Surgical intervention
Life threatening
bleeding
• Consider rFVIIa or PCC*
• Charcoal filtration* or
hemodialysis
*Recommendation based only on non-clinical
data (no experience in patients)
aPTT = activated partial thromboplastin time
TT=thrombin time
rFVIIa=recombinant factor VIIa
PCC=prothrombin complex concentrates
Bleeding continues
Adapted from:
1. van Ryn J, et al. Thromb Haemostat 2010;103:1116-1127
2. Hankey GJ & Eikelboom JW. Circulation 2011;123:1436-1450
3. Crowther MA & warkentin TE. J Thromb Hemostat 2009;7 (Suppl 1):107-110
4. Pradax Monograph 2010, Boehringer Ingelheim Canada Ltd
Summary/Conclusions
• Bleeding is the most common complication of antithrombotic therapy
• Prevention is better than cure
• Careful management of interruption and general measures are foundation
• Specific measures (hemostatic agents, charcoal, dialysis) are available but
will be rarely needed
• When considering anticoagulation, all AF patients should have appropriate
assessment of both stroke and bleeding risk using validated risk assessment
tools
• In cases of minor bleeding, hold 1 or 2 doses of the anticoagulant and
eliminate any unnecessary concomitant medications that may increase
bleeding risk
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