Mind the Gap: AF and
the Evolving Strategies
in Anticoagulation
In Cooperation with
Faculty Disclosures
Fred M. Kusomoto, MD, FACC
Mayo Clinic
Consulting Fees/Honoraria: Medtronic
Ralph J. Verdino, MD, FACC
University of Pennsylvania
Consulting Fees/Honoraria: Biosense Webster;
Biotronic, Inc.; Boston Scientific; Medtronic; St.
Jude Medical; Zoll
Officer, Director, Trustee or Other Fiduciary Role:
LifeWatch, Inc.
Acknowledgement
Boehringer Ingelheim Pharmaceuticals, Inc.
is a Founding Sponsor for the Mind the
Gap Forums.
“Atrial Fibrillation is the Low Back
Pain of Cardiology.”
Mike Crawford
Program Objectives
Upon completion of this session, attendees
should be able to —
•Implement evidence-based anticoagulation
regimens for atrial fibrillation patients based on
individual risks and patients’ preferences
•Recognize common barriers associated with
managing chronic anticoagulation in atrial
fibrillation patients
Atrial Fibrillation (AF) in the U.S
2.2 million people have AF
– 3.3 million in 2020; 5.6 million by 2050
– Above age 70: 10% incidence
– Lifetime risk: 25%
– Risk increases with increasing age
Future of Atrial Fibrillation
ATRIA Study
Projected Number of Adults With AF in the US 1995 to 2050
Adults With AF (millions)
7.0
6.0
5.0
4.34
4.0
4.78
5.16
5.42 5.61
3.80
3.0
2.0
2.08 2.26
2.44 2.66
2.94
3.33
1.0
0
1990 1995 2000 2005 2010 2015 2020 2025 2030 2035 2040 2045 2050
Year
Go et al. JAMA. 2001;285;2370-2375.
Prevalence
Incidence
Ann Int Med 1995
Biennial rate/1000
person exams
Age
Benjamin EJ JAMA 1994; Framingham Heart Study
Atrial Fibrillation in the U.S. (Cont.)
Risks/causative factors:
– HTN, DM, CHF, age, valvular heart disease,
MI, pulmonary embolus, cardiomyopathy,
pulmonary disease, hyperthyroidism
– Genetics: Most common in “Lone AF”
• Connexin-40
• Potassium channels: KCNQ1, KCNE2, KCNJ2,
KCNH2
• ANF peptide frame shift mutation
Atrial Fibrillation (AF) and Stroke
• Stroke is the most common and devastating
complication of AF1,2
• Incidence of all-cause stroke in patients with
AF is 5%1
• AF is an independent risk factor for stroke2
• Approximately 15% of all strokes in the US
are caused by AF3
1. Fuster V, et al. Circulation. 2006;114:e257-354.
2. Benjamin EJ, et al. Circulation. 1998;98:946-52.
3. Lloyd-Jones D, et al. Circulation. 2009;119:e21-181.
Stroke (%)
Stroke Rates in Placebo-Treated
Patients With AF*
AFASAK
SPAF
BAATAF
CAFA
SPINAF
EAFT†
*This represents patients who are not anticoagulated; †Secondary prevention.
Hart et al. Ann Intern Med. 1999;131:492-501.
Atrial Fibrillation and Stroke (Cont.)
• Risk of stroke increases with age1
• Ischemic stroke associated with AF is often
more severe than stroke of other etiologies4
• Stroke risk persists even in asymptomatic AF5
• Asymptomatic AF implicated as a cause of
cryptogenic stroke6
4. Dulli DA, et al. Neuroepidemiology. 2003;22:118-23.
5. Page RL, et al. Circulation. 2003;107:1141-5
6. Bhatt A, et al. Stroke Res Treat. 2011; 2011: 1-5
CHADS2
Congestive heart failure
Hypertension
Age >75 years
Diabetes mellitus
Prior Stroke or TIA (*2 points)
Gage, BF, et al. JAMA. 2001;285:2864-70
Stroke Risk in AF
ACP/AAFP Guidelines
CHADS2
Score
Adjusted Stroke Rate*
(95% CI)
CHADS2
Risk Level
0
1.9 (1.2-3.0)
Low
Aspirin
1
2.8 (2.0-3.8)
Low
Aspirin/Warfarin
2
4.0 (3.1-5.1)
Moderate
3
5.9 (4.6-7.3)
Moderate
4
8.5 (6.3-11.1)
5
12.5 (8.2-17.5)
High
6
18.2 (10.5-27.4)
High
*Expected
High
Warfarin
rate of stroke per 100 patient-years
Snow V, et al. Ann Intern Med. 2003;139:1009-17
CHADS2
Congestive heart failure
Hypertension
Age >75 years
Diabetes mellitus
Prior Stroke or TIA (*2 points)
Gage, BF, et al. JAMA. 2001;285:2864-70
CHADS2
Congestive heart failure
Hypertension
Age >75 years
Diabetes mellitus
Prior Stroke or TIA (*2 points)
CHADS2 did not consider other important risk factors:
–
–
–
–
–
Female gender (not confirmed in all studies)
Thyrotoxicosis
LA size
HOCM
Valvular heart disease
Gage, BF, et al. JAMA. 2001;285:2864-70
CHADS2
Lip et al Chest 2010
CHA2DS2-VASc
Clinical Feature
CHF
HTN
Age ≥ 75
Diabetes mellitus
Stroke, TIA, or embolism
Female gender
Age 65 - 74
Vascular disease (prior MI, PVD, aortic plaque
Points
1
1
2
1
2
1
1
1
CHADS2 vs. CHA2DS2-VASc
Lip et al Chest 2010
CHA2DS2VASc score
Adjusted stroke rate
(%/year)
Recommended
antithrombotic therapy
0
0
ASA 75-325mg or no
therapy. No therapy
preferred
1.3
Either oral anticoagulation
or ASA 75-325mg daily,
anticoagulation preferred
2
2.2
Oral anticoagulation
3
3.2
Oral anticoagulation
4
4.0
Oral anticoagulation
5
6.7
Oral anticoagulation
6
9.8
Oral anticoagulation
7
9.6
Oral anticoagulation
8
6.7
Oral anticoagulation
9
15.2
Oral anticoagulation
1
ESC Guidelines for
Antithrombotic Therapy
Europace 2010; 12: 1360-1420
Stroke Prevention: Coumadin
Warfarin
AFASAK
BAATAF
SPAF
CAFA
SPINAF
Warfarin/ASA
EAFT
SPAF II
AFASAK
Warfarin: Risk-Benefit Profile
20
Ischemic Stroke
Odds
Ratio
15
Intracranial Bleeding
10
5
1
1.0
2.0
3.0
4.0
5.0
6.0
7.0
8.0
INR
Fuster V, et al. Circulation. 2006;114:e257-354.
Warfarin and Drug Interactions
Warfarin is metabolized by the hepatic P450 enzyme CYP2C9
Warfarin concentration (and therefore INR) is increased by
drugs that inhibit CYP2C9. INR must be closely followed
and warfarin dosage decreased
CYP2C9 inhibitors include:
•
•
•
•
•
Amiodarone
Statins simvastatin and rosuvastatin (not atorvastatin, pravastatin)
Fibrates (fenofibrate, gemfibrozil)
Antibiotics (sulfamethoxazole/trimethoprim, metronidazole)
Azole antifungals (fluconazole, miconazole, voriconazole)
Warfarin and Drug Interactions (Cont.)
Drugs that induce CYP2C9: warfarin’s effectiveness is
decreased, reducing INR - Rifampin
• Other drugs interactions not via CYP2C metabolism Thyroid hormone
For more information visit www.qtdrugs.org (Arizona CERT) or
http://medicine.iupui.edu/clinpharm/ddis/table.asp (Indiana
University, Prof D.A. Flockhart)
Time Spent in
Therapeutic INR Range
(%)
Quality of Warfarin Control in AF Patients
on Chronic Anticoagulation
55%
63%
51%
Only 48% of eligible patients in this analysis received warfarin
Baker WL, et al. J Manag Care Pharm. 2009;15:244-52.
Time Spent in Therapeutic INR
Range and Clinical Outcomes
•
•
Groups stratified by time
spent in therapeutic INR
range (2.0-3.0)
All patients had a CHADS2
score ≥ 2
Morgan CL, et al. Thromb Res. 2009;124:37-41.
Warfarin in Eligible Patients
% Use in Eligible Patients
ATRIA Study
<55
55-64
Go et al. Ann Intern Med.
1999;131:927-934.
65-74
75-84
Age (years)
85
Overall
Warfarin in Eligible Patients
% Use in Eligible Patients
ATRIA Study
<55
55-64
Go et al. Ann Intern Med.
1999;131:927-934.
65-74
75-84
Age (years)
85
Overall
ACTIVE-W: Warfarin vs. Dual Antiplatelet
Therapy for Prevention of Cardiovascular Events
Cumulative risk of primary composite endpointa
Cumulative Hazard Rates
RR = 1.44 (1.18-1.76), P = 0.0003
Time (years)
aStroke,
MI, non-CNS systemic embolism, or vascular death.
ACTIVE Investigators. Lancet.
2006;367:1903-12.
ACTIVE-A: Dual Antiplatelet Therapy Reduces
Cumulative Incidence
the Incidence of Vascular Events in AF When
Warfarin Therapy Is “Unsuitable”
Primary Composite Endpointa
aStroke,
P = 0.01
Time (years)
Stroke
P < 0.001
Time (years)
MI, non-CNS systemic embolism, or vascular death.
ACTIVE Investigators. N Engl J Med. 2009;360:2066-78.
ACTIVE-A: Dual Antiplatelet Therapy
Increases the Risk of Bleeding
Bleeding Events
P<0.001
12
Percent/year
10
P<0.001
8
6
P<0.001
4
2
0
Major Bleeding
Minor Bleeding
ASA
ASA+clopidogrel
Any Bleeding
2011 Focused Update Recommendation
•Class IIb (New Recommendation)
•The addition of clopidogrel to aspirin (ASA) to reduce the
risk of major vascular events, including stroke, might be
considered in patients with AF in whom oral anticoagulation
with warfarin is considered unsuitable due to patient
preference or the physician’s assessment of the patient’s
ability to safely sustain anticoagulation. (Level of Evidence:
B)
•Single reference: ACTIVE A
2011 ACCF/AHA/HRS Focused Update on the Management of Patients with
Atrial Fibrillation (Updating the 2006 Guideline). Circulation 2011;123:104-123.
New Pharmacologic Approaches
for Stroke Reduction in AF
Oral direct thrombin inhibitors
– Fixed-dose, no monitoring
• Dabigatran
Oral factor Xa inhibitors
– Fixed-dose, no monitoring
• Apixaban
• Edoxaban
• Rivaroxaban
Antithrombotic Therapy in Atrial Fibrillation. Circulation 2011;75:1539-1547.
Direct Thrombin Inhibitors
Ximelagatran
– Tested in Stroke Prevention Using an Oral
Thrombin Inhibitor in Atrial Fibrillation
(SPORTIF) III (open label) and V (double
blind)
– Ximelagatran as effective as warfarin with
lower risk of bleeding
– Did not make it to market due to liver
toxicity
RE-LY: Randomized Evaluation of Longterm Anticoagulation Therapy
• 18,113 patients with atrial fibrillation randomized to
dabigatran (110 mg or 150 mg twice daily) versus
warfarin (INR target 2.0-3.0)
• Mean CHADS2 score = 2.1
• By intention-to-treat analysis dabigatran 110 mg was
non-inferior (p < 0.001) while dabigatran 150 mg was
superior( p<0.001) to warfarin
• INR was in the therapeutic range 64% of the time
NEJM 10.1056
RE-LY
“High risk” AF patients:
– At least one of:
• Prior CVA or TIA
• LVEF < 40%;
• NYHA Class I or greater CHF
• Age >75 yrs
• Age 65-74 and on of:
– DM
– HTN
– CAD
Exclusions: “severe valve disease;” CVA <14 days
or “severe CVA” <6 months; increased bleeding
risk; active liver disease; CrCl <30; pregnancy
Cumulative Hazard Rate
RE-LY: Dabigatran Reduces the
Risk of Stroke in AF Patients
Time (months)
Connolly SJ, et al. N Engl J Med. 2009;361:1139-51.
RE-LY: Safety Outcomes with Dabigatran
Dabigatran 110 mg
vs. Warfarin
Event
Dabigatran 150 mg
vs. Warfarin
RR (95% CI)
P value
RR (95% CI)
P value
Major bleeding
0.80 (0.69-0.93)
0.003
0.93 (0.81-1.07)
0.31
Life threatening
0.68 (0.55-0.83)
< 0.001
0.81 (0.66-0.99)
0.04
Gastrointestinal
bleeding
1.10 (0.86-1.41)
0.43
1.50 (1.19-1.89)
< 0.001
Major or minor
bleeding
0.78 (0.74-0.83)
< 0.001
0.91 (0.86-0.97)
0.002
Intracranial bleeding
0.31 (0.20-0.47)
< 0.001
0.40 (0.27-0.60)
< 0.001
Modified from Connolly SJ, et al. N Engl J Med. 2009;361:1139-51.
FDA Approval for Dabigatran:
• Dabigatran 150 was superior to warfarin and dabigatran
110 mg for stroke prevention;
• Dabigatran 150 mg was similar to warfarin for bleeding
risk but inferior to dabigatran 110 mg.
• Among the elderly (40% of Re-Ly patients over age 75),
thromboembolism risk was lower with dabi-150 than with
dabi-110, but bleeding risk was higher. Because bleeding is
“less undesirable” than stroke, dabi-110 not felt to be
advantageous.
Beasley BN, Unger EF, Temple R. Anticoagulant Options –
Why the FDA Approved a Higher but Not a Lower Dose of Dabigatran. NEJM 2011 (online first).
FDA Approval for Dabigatran:
75 mg q12h
• Among pts with impaired renal function (CrCl 30-50),
stroke risk for dabi-150 was 1/2 that of dabi-110 but
bleeding risk was not higher.
==> dabi-110 was not felt to offer any advantage, and it was
felt that most patients should receive the higher dosage.
• The decision to approve the 75 mg q12h dose was based
on pharmacokinetic and pharmacodynamic modeling;
there is no safety or efficacy data.
Beasley BN, Unger EF, Temple R. Anticoagulant Options –
Why the FDA Approved a Higher but Not a Lower Dose of Dabigatran. NEJM 2011 (online first).
Antithrombotic Therapy in Atrial Fibrillation. Circulation 2011;75:1539-1547.
Antithrombotic Therapy in Atrial Fibrillation. Circulation 2011;75:1539-1547.
Apixaban: AVERROES Trial
5599 patients with AF deemed “unsuitable” for warfarin
randomized to apixaban (5mg twice daily) or aspirin (81-324mg
daily)
Primary endpoint: stroke or systemic embolism
Trial terminated early due to superiority of apixaban
Apixaban
Aspirin
Percent/year
P<0.001
P<0.001
P=0.07
P=0.57
1.6 3.7
3.5 4.4
1.4 1.2
stroke/embolism
Death
major bleeding
12.6
15.9
CV hospitalization
Connolly et al. NEJM 2011 364: 806-17
ROCKET-AF: Rivaroxaban for the
Prevention of Stroke and Non-CNS Embolism
• 14,264 patients with atrial fibrillation randomized to
rivaroxaban (20mg once daily) versus warfarin (INR target
2.5)
• Mean CHADS2 score = 3.5
• By intention-to-treat analysis rivaroxaban was non-inferior
(p < 0.0001) but not superior ( p =0.12) to warfarin
• INR was in the therapeutic range only 55 percent of the
time
• Currently before the FDA for AF indication
• Safety: overall similar bleeding rates with less lifethreatening (fatal or intracranial) hemorrhage
NEJM 10.1056
2011 ACCF/AHA/HRS Focused Update on
the Management of Patients with Atrial
Fibrillation (Update on Dabigatran)
Case 1 – 76-year-old Female with
Dyspnea
• HPI
– Shortness of breath and DOE for several
months
– Denies palpitations, chest pain, or dizziness
• PMH
– Obesity, diabetes, HTN, chronic kidney
disease, hyperlipidemia, DJD
– Does not smoke or drink
– Meds: diltiazem, celecoxib, metformin,
pravastatin
• PE
– VS: BP 164/92, HR 94
– CV: irregularly irregular, no murmurs
• Data
– ECG: atrial fibrillation with controlled VR, LVH by
voltage
– BUN/Cr: 36/2.1, other labs incl LFTs nl
– CXR: mild cardiomegaly, o/w normal
– Stress echo: nl LV function, mild LVH, no sig valve dz,
no ischemia
Question
What is her risk of stroke?
a) High (~8-18%)
b) Medium (~4-6%)
c) Low (~2-3%)
Stroke Risk in AF
ACP/AAFP Guidelines
CHADS2
Score
Adjusted Stroke Rate*
(95% CI)
CHADS2
Risk Level
0
1.9 (1.2-3.0)
Low
Aspirin
1
2.8 (2.0-3.8)
Low
2
4.0 (3.1-5.1)
Moderate
Aspirin/
Warfarin
3
5.9 (4.6-7.3)
Moderate
4
8.5 (6.3-11.1)
High
5
12.5 (8.2-17.5)
High
6
18.2 (10.5-27.4)
High
*Expected
Warfarin
rate of stroke per 100 patient-years
Snow V, et al. Ann Intern Med. 2003;139:1009-17
CHA2DS2-VASc
Clinical Feature
CHF
HTN
Age ≥ 75
Diabetes mellitus
Stroke, TIA, or embolism
Female gender
Age 65 - 74
Vascular disease (prior MI, PVD, aortic plaque)
Points
1
1
2
1
2
1
1
1
ESC Guidelines for Antithrombotic Therapy
CHA2DS2VASc score
Adjusted stroke rate
(%/year)
Recommended
antithrombotic therapy
0
0
ASA 75-325mg or no
therapy. No therapy
preferred
1
ESC
Guidelines
for
1.3
Either oral anticoagulation
or ASA 75-325mg daily,
Antithromboticanticoagulation
Therapy
preferred
2
2.2
Oral anticoagulation
3
3.2
Oral anticoagulation
4
4.0
Oral anticoagulation
5
6.7
Oral anticoagulation
6
9.8
Oral anticoagulation
7
9.6
Oral anticoagulation
8
6.7
Oral anticoagulation
9
15.2
Oral anticoagulation
Europace 2010; 12: 1360-1420
Question
What is her risk of bleeding with
anticoagulation?
a) High
b) Medium
c) Low
HAS-BLED Score
Clinical Feature
Points
SBP ≥ 160 mmHg
1
Abnormal renal function
1
Abnormal liver function
1
Prior CVA
1
Bleeding
1
Labile INRs
1
Age > 65
1
Taking antiplatelets/NSAIDs
1
Alcohol intake
1
HAS-BLED score ≥3 indicates increased one year risk of
intracranial bleed, bleed requiring hospitalization, or drop in
hemoglobin ≥2gm/L or requiring transfusion.
HAS-BLED score in the
SPORTIF cohort
%
Score
Lip et al JACC 2011
Question
What is her risk of stroke/bleeding?
a) CHADS2 score=3 (annual stroke
risk=5.9%)
b) CHADS2VASc=5 (annual stroke
risk=6.7%)
c) 3. HASBLED score=4 (annual bleeding
risk=5.6%)
Question
Which anticoagulation regimen is
most appropriate for her?
a)
b)
c)
d)
e)
Aspirin
Warfarin
Dabigatran 75mg twice daily
Dabigatran 150 mg twice daily
Aspirin/clopidogrel
AF and Strokes
• 15% of ischemic strokes are due to
cardioemboli => 75,000 events/year
• 45% of cardioemboli are due to atrial
fibrillation
• Risk of stroke 5-7x increased in patients
with atrial fibrillation
Which Anticoagulation Regimen is Most
Appropriate for Her?
http://www.vhpharmsci.com/sparc/
Which Anticoagulation Regimen to Use?
http://www.vhpharmsci.com/sparc/
Which Anticoagulation Regimen to Use?
http://www.vhpharmsci.com/sparc/
Case 1 Teaching Points
• When using oral anticoagulants, balancing the
risks of bleeding vs the risks of stroke can be
difficult.
• Scoring systems that predict risk (CHADS2,
CHA2DS2Vasc, HASBLED) can help with
decision making.
Questions and Answers
Case 2 – 59-year-old Man Presents
with Acute Chest Pain
Past History
- 10
years ago first diagnosed with
hypertension
- 5 years ago acute inferior MI
Cath showed - 95% RCA
70% LAD
90% OM1
Underwent CABG x3
- 6 month f/u - EF 40% by echo with inferior
and posterior severe hypokinesia
Past History (Cont.)
-4
years ago nuclear stress showed EF 35-40%,
inferior and posterior scar without ischemia
diminished functional status
- 6 months ago maintained on Lisinopril 40
mgqd, Carvedilol 20 q12h, Aspirin 81mgqd,
Simvastatin 40 mgqd, NYHA Class III CHF
symptoms
- 3 months ago presented on OV with atrial
fibrillation with controlled rate; warfarin begun
Present Coronary Anatomy
Native coronaries
100% RCA
95% prox LAD
100% OM1
95% proximal LCx stenosis
- Patent LIMA and LAD, graft to PDA
- Occluded graft to OM1
- Placed on clopidogrel full dose aspirin and
underwent PCI of LCx with bare metal stent
Question
What would you do next?
a) Continue warfarin indefinitely with aspirin, clopidogrel
for one year
b) Substitute dabigatran with aspirin, clopidogrel for one
year
c) Stop warfarin, aspirin and clopidogrel for one month
and resume warfarin
d) Stop warfarin, aspirin and clopidogrel for one month
then add dabigatran
Triple Rx:
Bleeding and Mortality in a Danish Registry after MI
Sorensen et al Lancet 2009
Question
What would you do next?
a) Continue warfarin indefinitely with aspirin, clopidogrel
for one year
b) Substitute dabigatran with aspirin, clopidogrel for one
year
c) Stop warfarin, aspirin and clopidogrel for one month
and resume warfarin
d) Stop warfarin, aspirin and clopidogrel for one month
then add dabigatran
Guidelines for the Management of Atrial Fibrillation. European Heart Journal 2010; 31: 2369 - 2429.
Guidelines for the Management of Atrial Fibrillation. European Heart Journal 2010; 31: 2369 - 2429.
Risk Management:
Stent Thrombosis vs. Bleeding vs. Stroke
Faxon et al Hemostasis and Thrombosis 2011.
Managing Risk
• Stent Thrombosis
• Discontinuing DAPT
• Procedural: TIMI < 3, Discontinuing DAPT,
residual dissection, bifurcations stents, incomplete stent
apposition, stent length, proximal dz
• Patient: Malignancy, diabetes, renal failure
• Bleeding
• HAS-BLED
• Stroke
• CHADS2 or CHA2DS2-VASc
Risk Management:
Stent Thrombosis vs. Bleeding vs. Stroke
Faxon et al Hemostasis and Thrombosis 2011.
Randomized Trials on Triple Therapy
• ISAR-TRIPLE:
600 patients after DES will be randomized to either a short
course (6 weeks) or long course (6 months), followed by aspirin
and warfarin. 1°: Composite of death, MI, definite stent
thrombosis, or major bleeding at 9 months
• WOEST:
496 patients randomized oral anticoagulation and clopidogrel or
triple therapy. 1°: Bleeding at 1 year
• MUSICA-2:
304 patients (CHADS≤ 2) randomized to DAPT or triple
Rx
Case 2 Teaching Points
• Choose BMS if patient will require antithrombotic therapy long term
• Presentation with ACS implies that patient
should ideally be treated with dual anti-platelet
therapy for 1 year but needs to be judged
relative to bleeding risk
• Data on triple therapy is limited
• No data on dabigitran in this setting and
nothing in guidelines
Questions and Answers
Mind the Gap: Summary
• Atrial fibrillation is going to become more
common
• Stroke is the most devastating complication of
atrial fibrillation
• Old and new options
• Managing patients in “real life” is difficult
Case 3 – 80-year-old Male with
Renal Cell Cancer
HPI
Renal cell cancer recently diagnosed
Nephrectomy is planned
Urologic surgeon requests peri-op cardiac management
PMH
Permanent atrial fibrillation for > 5 years, managed with
metoprolol and warfarin
Meds: metoprolol, warfarin, lisinopril, pravastatin, aspirin
Physical Exam
VS: BP 134/68, HR 78 irreg irreg
CV: irregularly irregular, no murmurs
Data
ECG: atrial fibrillation with controlled VR
INR 2.3
Question
In preparation for surgery, you
should:
a)Admit the patient to the hospital, stop
warfarin and administer IV heparin until the
morning of surgery
b)Stop warfarin 5 days prior to surgery and
initiate LMWH until the morning of surgery
c)Stop warfarin 5 days prior to surgery without
bridging anticoagulation
Risks Associated with Temporary
Discontinuation of Warfarin
• After warfarin is stopped, it takes about 4 days for the
INR to reach 1.5.
• Once the INR is 1.5 surgery can be safely performed.
• Therefore, if warfarin is held 4 days before surgery and
treatment is started as soon as possible after surgery,
patients can be expected to have a subtherapeautic INR
for two days before and two days after surgery.
ACC/AHA/ESC 2006 Guidelines
for Perioperative Management of
Atrial Fibrillation
• Anticoagulation may be interrupted for a
period of up to one week for surgery.
• In high risk patients (prior stroke, TIA,
or systemic embolism) unfractionated or
low-molecular-weight heparin may be
used.
ACCP 8th Edition Evidence-Based Clinical Practice
Guidelines: Managing Non-therapeutic INRs
For patients with INRs of ≥ 5.0 but < 9.0 and no
significant bleeding:
–Omit the next one or two doses of warfarin
–Monitor more frequently
–Resume therapy at an appropriately adjusted dose
when the INR is at a therapeutic level (Grade 1C)
–Alternatively, omit a dose and administer 1 to 2.5
mg oral vitamin K, particularly if the patient is at
increased risk of bleeding (Grade 2A)
Ansell J, et al. Chest. 2008;133:160S-98S.
Peri-operative Management of Dabigatran
• With normal kidney function, miss two doses
of dabigatran before surgery.
• With impaired kidney function, miss 3-4
doses of dabigatran before surgery.
• If surgery carries a high risk of bleeding,
consider stopping dabigatran 2 days before
surgery with normal renal function and 3-5
days with impaired renal function.
Question
What would you do?
a) Initiate a rhythm control drug
b) Discharge on beta-blocker alone
Case 3 Teaching Points
• Most patients, unless they have had prior
stroke, TIA, or systemic embolism do not
require bridging of anticoagulation.
• Warfarin can be stopped for 5 days prior to
surgery while dabigatran can be stopped just 12 days prior to surgery.