Transcript Presentation Slides

Evidence-based Recommendations
The practice recommendations in this presentation are from:
European Society of Cardiology
Source: Guidelines for the Management of Atrial Fibrillation.
European Heart Journal 2010;31:2369-429.
Website: http://www.escardio.org/guidelines-surveys/escguidelines/GuidelinesDocuments/guidelines-afib-FT.pdf
Strength of Evidence: The strength of evidence is indicated
following each recommendation.
Evidence-based Recommendations
American College of Cardiology, American Heart Association
Task Force on Practice Guidelines and European Society of
Cardiology Committee for Practice Guidelines
Source: ACC/AHA/ESC 2006 Guidelines for the Management of
Patients with Atrial Fibrillation. Circulation 2006;114:e257-e354.
Website: http://circ.ahajournals.org/cgi/content/full/114/7/e257
Strength of Evidence: The strength of evidence is indicated
following each recommendation.
Evidence-based Recommendations
American College of Cardiology Foundation, American Heart
Association Task Force on Practice Guidelines
Source: 2011 ACCF/AHA/HRS Focused Update on the Management of
Patients with Atrial Fibrillation (Updating the 2006 Guideline). Circulation
2011;123:104-23.
Website: http://circ.ahajournals.org/cgi/content/short/123/1/104
Strength of Evidence: The strength of evidence is indicated following
each recommendation.
Evidence-based Recommendations
American College of Cardiology Foundation, American Heart
Association Task Force on Practice Guidelines
Source: 2011 ACCF/AHA/HRS Focused Update on the Management
of Patients with Atrial Fibrillation (Update on Dabigatran). J Am Coll
Cardiol 2011;57:1330-7.
Website:
http://content.onlinejacc.org/cgi/content/full/j.jacc.2011.01.010
Strength of Evidence: The strength of evidence is indicated
following each recommendation.
Evidence-based Recommendations
American College of Chest Physicians
Source: Antithrombotic Therapy in Atrial Fibrillation. Chest
2008;133(Suppl 6):546S-92S.
Website:
http://chestjournal.chestpubs.org/content/133/6_suppl/546S.full
Strength of Evidence: The strength of evidence is indicated following
each recommendation.
To Anticoagulate or Not to Anticoagulate?
Module 1
Case 1
55-year-old male with lone
atrial fibrillation
Case 1
• 55-year-old male comes to the office stating that he has had
two days of palpitations. He denies chest pain or shortness
of breath.
• Past medical history: negative
• Medications: none
• Family history: father died of an MI at 80 years of age;
mother is alive and well
Case 1 (continued)
• Social history: works as a financial advisor, no tobacco use,
social drinker (few drinks a week)
• Physical exam:
–
–
–
–
–
Pulse: 105 irregular
BP: 130/74 mm Hg
Respiratory rate: 14
CV: irregularly irregular without murmurs
Lungs: clear
• Electrocardiogram: atrial fibrillation at rate of 104
Case 1: ECG
CHADS2 Scoring
Points
C
CHF
1
H
Hypertension
1
A
Age ≥75
1
D
Diabetes
1
S
Stroke or TIA
2
CHF = congestive heart failure; TIA = transient ischemic attack.
Information from Gage BF, et al. JAMA 2001;285:2864-70.
CHADS2 Application
CHADS2
Score
Adjusted Stroke Rate
(per 100 patient years)
95%
Confidence
Interval
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
Information from Gage BF, et al. JAMA 2001;285:2864-70.
CHADS2 and Recommended Therapy
CHADS2 Score
0
1
≥2
Recommended Therapy
Aspirin (75 mg-325 mg daily)
Aspirin (75 mg-325 mg daily) or
Warfarin (INR 2.0-3.0)
Warfarin (INR 2.0-3.0)
Aspirin or no therapy is acceptable for patients less than 60 years of age with no
heart disease (lone AF).
Singer DE, et al. Chest 2008;133(suppl 6):546S-92S.
Aspirin
• Stroke reduction compared with placebo
– Aspirin: 14% to 22%
– Warfarin: 62%
• Bleeding risk
– Aspirin: 1.3 per 100 patient years (lethal bleeding = 0.2)
– Warfarin: 2.2 per 100 patient years (lethal bleeding = 0.4)
Hart RG, et al. Ann Intern Med 1999;131:492-501.
EAFT Study Group. Lancet 1993;342:1255-62.
Petersen P, et al. Lancet 1989;333:175-9.
Van Walraven C, et al. JAMA 2002;288:2441-8.
Gulløv AL, et al. Arch Intern Med 1999;159:1322-8.
Evidence-based Recommendations
Recommendation #1: The CHADS2 score is recommended as
a simple initial means of assessing stroke risk in nonvalvular
atrial fibrillation (AF). (I A)
Recommendation #2: Patients with no risk factors (essentially
patients aged <65 years with lone AF, with none of the risk
factors) are at low risk of stroke. In these patients, the use of
aspirin, 75 mg–325 mg daily, or no antithrombotic therapy, is
recommended. (I B)
ESC. European Heart Journal 2010;31:2369-429.
Evidence-based Recommendation
Recommendation #3: Antithrombotic therapy to prevent
thromboembolism is recommended for all patients with AF,
except those with lone AF or contraindications. (I A)
ACC/AHA/ESC. Circulation 2006;114:e257-354.
Choice of Anticoagulant
Module 2
Case 2
65-year-old male with hypertension
Case 2
• 65-year-old male with a history of hypertension presents for
routine follow-up and is noted to have an irregular pulse. He
denies chest pain or shortness of breath.
• Past medical history
– Hypertension
– Peptic ulcer disease treated approximately 5 years ago
– Intermittent GERD
• Medications
– Hydrochlorothiazide, 12.5 mg daily
– Lisinopril, 5 mg daily
– Omeprazole OTC, 10 mg as needed
Case 2 (continued)
• Social history: retired schoolteacher, denies tobacco use,
rare alcohol use
• Physical exam:
–
–
–
–
General: alert, oriented, comfortable
Pulse: 95
BP: 138/86 mm Hg
CV: irregularly irregular with 2/6 systolic blowing murmur at the
apex
• Electrocardiogram: atrial fibrillation with a heart rate of 95,
possible left ventricular hypertrophy
Case 2: ECG
Cumulative Mortality (%)
Mortality: Rhythm vs. Rate Control (AFFIRM trial)
30
P=0.08
25
20
Rhythm Control
15
Rate Control
10
5
0
0
1
2
3
4
5
Years
AFFIRM = Atrial Fibrillation Follow-up Investigation of Rhythm Management.
Reprinted with permission from Wyse DG, et al. N Engl J Med 2002;347:1825-33.
Management with the rhythm-control
strategy offers no survival advantage
over the rate-control strategy, and
there are potential advantages, such
as a lower risk of adverse drug
effects, with the rate-control strategy.
CHADS2 and Recommended Therapy
CHADS2 Score
0
1
≥2
Recommended Therapy
Aspirin (75 mg-325 mg daily)
Aspirin (75 mg-325 mg daily) or
Warfarin (INR 2.0-3.0)
Warfarin (INR 2.0-3.0)
Aspirin or no therapy is acceptable for patients less than 60 years of
age with no heart disease (lone AF).
Singer DE, et al. Chest 2008;133(suppl 6):546S-92S.
Cumulative Hazard Rate
Stroke/Systemic Embolization: Dabigatran vs. Warfarin
Figure shows data from the RE-LY study,
displaying cumulative hazard rates for the
primary outcome of stroke or systemic embolism.
0.05
0.04
Dabigatran
110 mg
0.03
Warfarin
Primary outcome results
Warfarin = 1.69% per year
Dabigatran (150 mg twice daily) = 1.11% per year
0.02
Dabigatran
150 mg
0.01
0.00
0
6
12
18
Months
24
30
RE-LY = The Randomized Evaluation of Long-Term Anticoagulation Therapy.
Reprinted with permission from Connolly S, et al. N Engl J Med 2009;361:1139-51.
(P<0.001 for superiority; RR: 0.66)
Rates of major bleeding
Warfarin = 3.36% per year
Dabigatran (150 mg twice daily) = 3.11% per year
(P=0.31)
Comparing Dabigatran and Warfarin
Characteristic
Dabigatran
Warfarin
Dosing
Twice daily
According to INR
Monitoring
Half-life
Yes
Mean: 40 hours
Elimination
No
13 hours (normal renal
function)
Renal
Drug-drug interactions
Few
Numerous
Drug-food interactions
None noted in the
prescribing information
Numerous
U.S. prescribing information for dabigatran and warfarin, 2010.
Hepatic
Evidence-based Recommendation
Recommendation #4: Anticoagulation is recommended for patients
with more than one moderate risk factor. Such risk factors include
age 75 years or greater, hypertension, heart failure, impaired left
ventricular systolic function (ejection fraction 35% or less, or
fractional shortening less than 25%), and diabetes mellitus. (I A)
ACC/AHA/ESC. Circulation 2006;114:e257-354.
Case 3
70-year-old female
The Impact of Patient Factors on Choice of
Anticoagulant
Module 3
Case 3
• 70-year-old female presents with two weeks of palpitations
without shortness of breath or chest pain.
• Past medical history
– Hypertension
– Hypercholesterolemia
– Congestive heart failure (ejection fraction: 35%)
• Medications
– Metoprolol, 50 mg twice daily
– Lisinopril, 20 mg daily
– Atorvastatin, 20 mg daily
Case 3 (continued)
• Social history: lives with her husband, neither drives; does
not smoke or use alcohol
• Physical exam:
–
–
–
–
–
–
General: alert, interactive, comfortable
BP: 128/78 mm Hg
Pulse: 80
RR: 16
Lungs: clear
CV: irregularly irregular with II/VI systolic murmur left upper
sternal border
• Electrocardiogram: atrial fibrillation with rate 76
Rate vs. Rhythm Control in CHF
Kaplan–Meier Estimates of Death from Cardiovascular Causes (Primary Outcome)
Survival Rate (%)
100
Rate Control
• Similar outcomes to AFFIRM
• No evidence-based benefit
of rhythm control over rate
control in CHF
- No survival advantage
- No outcomes advantage
80
Rhythm Control
60
P=0.59
40
20
0
0
12
24
36
48
Months of Follow-up
60
Reprinted with permission from Roy D, et al. N Engl J Med 2008;358:2667-77.
Dabigatran: Practical Aspects
• Dosing and creatinine clearance
>30 ml/min: 150 mg twice daily
15-30 ml/min: 75 mg twice daily
<15 ml/min: Do not use
• No need for blood level monitoring
• Therapeutic level reached within 30 minutes to 2 hours
U.S. prescribing information for dabigatran, 2010.
Dabigatran: Practical Aspects (continued)
• Switching from warfarin to dabigatran
– Not much guidance yet available
– Wait until INR is below 2.0, then start dabigatran
• Surgery
– Creatinine clearance ≥50 ml/min: Skip doses for 1-2 days
before surgery
– Creatinine clearance <50 ml/min: Skip doses for 3-5 days
before surgery
U.S. prescribing information for dabigatran, 2010.
Evidence-based Recommendation
Recommendation #5: In patients with atrial fibrillation (AF), including
those with paroxysmal AF, who have two or more of the following risk
factors for future ischemic stroke, the guidelines recommend longterm anticoagulation with an oral vitamin K antagonist, such as
warfarin, targeted at an INR of 2.5 (range: 2.0 to 3.0) because of the
increased risk of future ischemic stroke faced by this set of patients.
(1A)
Risk factors: Age >75 years, history of hypertension, diabetes
mellitus, and moderately or severely impaired left ventricular systolic
function and/or heart failure
ACCP. Chest 2008;133(Suppl 6):546S-92S.
Evidence-based Recommendation
Recommendation #6: Dabigatran is useful as an alternative to
warfarin for the prevention of stroke and systemic thromboembolism
in patients with paroxysmal to permanent atrial fibrillation and risk
factors for stroke and systemic thromboembolism who do not have a
prosthetic heart valve or hemodynamically significant valve disease,
severe renal failure (creatinine clearance <15ml/min), or advanced
liver disease (impaired baseline clotting function). (I B)
ACCF/AHA/HRS. J Am Coll Cardiol 2011;57:1330-7.
Balancing Benefit and Risk
Module 4
Case 4
85-year-old female with multiple comorbidities
Case 4
• 85-year-old female presents for routine physical exam. She
has no complaints, and denies chest pain or shortness of
breath.
• Past medical history
–
–
–
–
Hypertension
Coronary artery disease
Congestive heart failure
Degenerative joint disease with ambulatory dysfunction
Case 4 (continued)
• Medications
–
–
–
–
Atenolol, 25 mg daily
Lisinopril, 10 mg daily
Hydrochlorothiazide, 12.5 mg daily
Aspirin, 81 mg daily
• Social history: lives in assisted living and has had numerous
falls in past six months; does not smoke or drink alcohol
Case 4 (continued)
• Physical exam
-
General: comfortable and interactive
BP: 130/80 mm Hg
Pulse: 80
Lungs: clear
CV: irregularly irregular with I/VI systolic murmur
• Electrocardiogram: atrial fibrillation with rate 104
Aspirin Plus Clopidogrel (ACTIVE A Trial)
• Aspirin (75 mg-100 mg daily) plus
clopidogrel (75 mg daily) reduced stroke
risk by 28%
- Aspirin stroke risk: 3.3% per year
- Combination therapy stroke risk: 2.4%
per year
Cumulative Incidence
1.0
0.8
0.6
• 2.0% per year incidence of major
bleeding (vs. 1.3% with aspirin alone)
0.4
P<0.001
0.2
0.0
Aspirin Only
Clopidogrel Plus Aspirin
0
1
2
3
4
Years
Adapted with permission from Connolly S. N Engl J Med 2009;360:2066-78.
Evidence-based Recommendation
Recommendation #7: The selection of antithrombotic agent should
be based on the absolute risks of stroke and bleeding, and the
relative risk and benefit for a given patient. (I A)
ACC/AHA/ESC. Circulation 2006;114:e257-354.
Evidence-based Recommendation
Recommendation #8: The addition of clopidogrel to aspirin to
reduce the risk of major vascular events, including stroke, might be
considered in patients with atrial fibrillation in whom oral
anticoagulation with warfarin is considered unsuitable due to patient
preference or physician assessment of the patient’s ability to safely
sustain anticoagulation. (IIb B)
ACCF/AHA/HRS. Circulation 2011;123:104-23.
Final Comments: Rate vs. Rhythm
• There is no significant difference in outcomes for patients,
either with or without congestive heart failure, with a strategy
of either rate control or rhythm control.
Roy D, et al. N Engl J Med 2008;358:2667-77.
Wyse DG, et al. N Engl J Med 2002;347:1825-33.
Final Comments: Thromboprophylaxis
• Assess ALL patients with atrial fibrillation for risk of stroke
- Patients with low risk of stroke (CHADS2 score = 0): do not need
anticoagulation and may be managed with an antiplatelet agent
- All others need anticoagulation, unless there are
contraindications
- Patients with moderate risk (CHADS2 score = 1): either an
antiplatelet or anticoagulation agent is appropriate
Thromboprophylaxis (continued)
• For patients in whom anticoagulation is contraindicated, an
antiplatelet agent is recommended:
- Either aspirin or clopidogrel
- There may also be a place for the combination of aspirin plus
clopidogrel
- Combination decreases risk of stroke but increases risk of major
bleeds compared to aspirin alone (Connolly S. N Engl J Med
2009;360:2066-78.)
Thromboprophylaxis (continued)
• Patients with CHADS2 score ≥2 – or patients with score of 1
in whom anticoagulation is indicated – two anticoagulant
agents are available.
- Dabigatran
- Warfarin
Thromboprophylaxis (continued)
• Decision of which anticoagulant medication to use should be
made on an individual basis
- Dabigatran has lower risk of stroke and systemic embolism
compared with warfarin
- Same major bleeding risk at 150 mg twice daily
Connolly SJ, et al. N Engl J Med 2009;361:1139-51.
Wann LS, et al. Circulation 2011;123:1144-50.