mind the gap: af and evolving strategies in anticoagulation

Title of Presentation goes here: 2 Line Title Goes Here 3 Line Title Goes Here.Director, Cardiac Electrophysiology
West Virginia University
Premier Healthcare, LLC
Indiana University
Bloomington, Ind.
Faculty Disclosures
Robert W. Hull, MD, FACC Nothing to disclose John S. Strobel, MD, FACC Consultant Fees/Honoraria: Boehringer Ingelheim; Bristol-Myers Squibb; Pfizer Inc; sanofi-aventis U.S. Inc.
Acknowledgement
This activity is sponsored by Boehringer Ingelheim Pharmaceuticals, Inc. and Janssen Pharmaceuticals, Inc.
Course 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
The Anticoagulation Initiative
• A multidisciplinary effort to identify and address gaps in the quality of anticoagulation care
• Purpose is to facilitate a greater understanding of AF treatments and practice patterns, particularly with the introduction of several new anticoagulants into the marketplace
• This initiative is building on existing resources (i.e., the AFib Toolkit) and creating new resources (i.e., anticoagulation mobile app)
AnticoagEvaluator:
An ACC Risk Assessment Tool • Tool for estimating risk of stroke and benefits and risks of
antithrombotic therapy in patients with chronic atrial fibrillation
• Combination risk calculator using CHADS2, CHA2DS2-VASc
and HAS-BLED • Enter patient characteristics and get individualized annual
risk of ischemic stroke and thromboembolism with concurrent annual risk of major bleed
AnticoagEvaluator:
• Output presents antithrombotic therapy options including
novel oral anticoagulants based on clinical trials (RE-LY, ROCKET-AF, ARISTOTLE)
• Email individual patient results after completing risk
calculator tool
AnticoagEvaluator: Calculators
Enter patient characteristics into single screen to calculate risk of stroke and major bleed:
AnticoagEvaluator: Results Screen
Review risk assessment for each antithrombotic therapy option based on individual patient characteristics entered:
Instructions to Download
• Available on iPad, iPhone, and Android devices
– Features relevant news articles, case challenges, hot topics, basics of anticoagulation, videos, interactive discussion, resources to clinicians, and more
– Dr. Robert Giugliano, Brigham and Women's Hospital, contracted to serve as editor
– Available at http://anticoagulation.cardiosource.org/
The Anticoagulation Initiative:
– Patient-centered decision aid being developed in partnership with the Informed Medical Decisions Foundation
– Launching in late 2013
b) 5-10
c) 10-20
What anticoagulants/antiplatelet agents do you most frequently use to prevent thromboembolic complications? a) Aspirin
b) Aspirin/clopidogrel
e) Warfarin
f) Other
Question 2
Over the last nine months, when appropriate for your atrial fibrillation patients, have you found yourself making any of the following changes? a) Switching some patients’ medication to a newer agent
b) Switching most patients from existing medication to a newer agent
c) No change in prescribing pattern, current medication successful in treatment
d) No change in prescribing pattern, waiting for more data on newer agents
Question 3
What is the primary thing you might do differently in treating your AF patients? a) Increase my utilization of long-term anticoagulation in my at- risk atrial fibrillation patients
b) Work to better assess the thromboembolic risk in my atrial fibrillation patients
c) Explain to my patients the pros and cons of different anticoagulation agents
d) Better communicate the risk of stroke to my atrial fibrillation patients and the importance of anticoagulation
e) Nothing – I feel my level of patient care is appropriate
Question 4
What might impede you most from making this change? a) Time constraints
b) Low priority compared to other patient management issues
c) Difficulty in changing patient behavior
d) Difficulty in getting patients to accept the benefits of long-term anticoagulation
e) Cost of medication
f) Cost of monitoring (blood tests, dosage adjustments) for patients on anticoagulation
g) Lack of data on or experience with newer agents
h) No change necessary
Question 5
A 72-year-old male with a history of persistent atrial fibrillation for the past five (5) years is currently being treated with warfarin anticoagulation and a beta blocker for rate control. He comes to you to ask about switching to a new anticoagulant drug that does not require INR monitoring.
Question 6
Given the following patient characteristics, in which setting would switching from warfarin to a Novel Oral Anticoagulant (NOAC) be appropriate and supported by clinical data?
a) Ejection fraction of 30% with Class II heart failure
b) Normal functioning mechanical MVR
c) LVH with EF 55%; chronic renal insufficiency with creatinine clearance 10 ml/min
Question 6 (Cont.)
– 3.3 million in 2020; 5.6 million by 2050
– Above age 70: 10% incidence
– Lifetime risk: 25%
Atrial Fibrillation (AF) in the U.S.
• 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
• ANF peptide frame shift mutation
Atrial Fibrillation in the U.S. (Cont.)
Ann Int Med 1995
Incidence
Benjamin EJ JAMA 1994; Framingham Heart Study
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.
Atrial Fibrillation and Stroke
• 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
• 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
Atrial Fibrillation and Stroke (Cont.)
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
• CHADS2 did not consider other important risk factors:
– Female gender (not confirmed in all studies)
– Thyrotoxicosis
Stroke Risk in AF ACP/AAFP
Guidelines
*Expected rate of stroke per 100 patient-years
CHA2DS2-VASc
ESC Guidelines for Antithrombotic Therapy
Europace 2010; 12: 1360-1420 European Heart Journal (2012) 33, 2719–2747
Stroke Prevention: Coumadin
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:
• 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)
Quality of Warfarin Control in
AF Patients on Chronic Anticoagulation
Baker WL, et al. J Manag Care Pharm. 2009;15:244-52. Only 48% of eligible patients in this analysis received warfarin
Time Spent in Therapeutic INR
Range and Clinical Outcomes
Warfarin and Novel Anticoagulant
Mechanisms of Action
Courtesy of David Garcia, MD *This information includes a use that has not been approved by the U.S. FDA
Case 1
– Denies palpitations, chest pain or dizziness
• PMH
– Does not smoke or drink
– Meds: diltiazem, celecoxib, pravastatin, aspirin
• PE
• Data
– BUN/Cr: 36/2.1, GFR 23 ml/min, other labs incl LFTs nl
– CXR: mild cardiomegaly, o/w normal
– Stress echo: nl LV function, mild LVH, no sig valve dz, no ischemia
a) High (~8-18%)
b) Medium (~4-6%)
c) Low (~2-3%)
Question
Snow V, et al. Ann Intern Med. 2003;139:1009-17
CHA2DS2-VASc
Female gender 1
ESC Guidelines for Antithrombotic Therapy
CHA2DS2VASc score Adjusted stroke rate (%/year) Recommended antithrombotic therapy
0 0 No therapy
1 1.3 Oral anticoagulation
Europace 2010; 12: 1360-1420 European Heart Journal (2012) 33, 2719–2747
a) High
b) Medium
c) Low
Question
Labile INRs 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.
What is her risk of stroke/bleeding?
a) CHADS2 score=0 (annual stroke risk=1.9%) b) CHA2DS2VASc=3 (annual stroke risk=3.2%) c) HASBLED score=3 (annual bleeding risk=5.6%)
Question
a) Aspirin
b) Warfarin
c) NOAC
d) Aspirin/clopidogrel
Anticoagulation Recommendations for Atrial Fibrillation
Pamela K. Mason, MD, Douglas E. Lake, PhD, John P. DiMarco, MD, PhD, John D. Ferguson, MBChB, MD, J. Michael Mangrum, MD, Kenneth Bilchick, MD, Liza P. Moorman, RN, ACNP-BC, J. Randall Moorman, MD University of Virginia Health System, Charlottesville.
Figure 1 Distribution of the CHADS2 and CHA2DS2-VASc scores among women (A) and men (B). The American Journal of Medicine 2012 125, 603.e4
Impact of the CHA2DS2-VASc Score on
Anticoagulation Recommendations for Atrial Fibrillation
Pamela K. Mason, MD, Douglas E. Lake, PhD, John P. DiMarco, MD, PhD, John D. Ferguson, MBChB, MD, J. Michael Mangrum, MD, Kenneth Bilchick, MD, Liza P. Moorman, RN, ACNP-BC, J. Randall Moorman, MD University of Virginia Health System, Charlottesville.
Figure 2 Anticoagulation recommendations by CHADS2 and CHA2-DS2-VASc scores in women (A) and men (B). The American Journal of Medicine 2012 125, 603.e4
Which Anticoagulation Regimen Is
Most Appropriate for Her?
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
for Prevention of Cardiovascular Events
Cumulative risk of primary composite endpointa
aStroke, MI, non-CNS systemic embolism or vascular death ACTIVE Investigators. Lancet. 2006;367:1903-12.
ACTIVE-A: Dual Antiplatelet Therapy
Warfarin Therapy Is “Unsuitable”
ACTIVE Investigators. N Engl J Med. 2009;360:2066-78
ACTIVE-A: Dual Antiplatelet
0
2
4
6
8
10
12
P e
rc e
n t/
ye ar
Bleeding Events
• 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.
2011 Focused Update Recommendation
• Oral direct thrombin inhibitors
– Fixed-dose, no monitoring • Dabigatran
• Oral factor Xa inhibitors
RE-LY: Randomized Evaluation of
Long-Term 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
• Prior CVA or TIA
• Age >75 yrs
– DM
– HTN
– CAD
• Exclusions: “severe valve disease;” CVA <14 days or “severe CVA” <6 months; increased bleeding risk; active liver disease; CrCl <30; pregnancy
RE-LY: Dabigatran Reduces the Risk of
Stroke in AF Patients
RE-LY: Safety Outcomes with Dabigatran
Modified from Connolly SJ, et al. N Engl J Med. 2009;361:1139-51.
FDA Approval for Dabigatran:
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).
• 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
FDA Approval for Dabigatran:
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).
• 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
2011 ACCF/AHA/HRS Focused Update
(Update on Dabigatran)
• 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
NEJM 10.1056
Prevention of Stroke and Non-CNS Embolism
• INR was in the therapeutic range only 55 percent of the time
• Approved by FDA
• Safety: overall similar bleeding rates with less life- threatening (fatal or intracranial) hemorrhage
Cumulative Rates of the Primary End Point
(Stroke or Systemic Embolism) in the Per-protocol
Population and in the Intention-to-Treat Population
Manesh et al. NEJM 2011 365: 883-891
Cumulative Rates of the Primary End Point
(Stroke or Systemic Embolism) in the Per-protocol
Population and in the Intention-to-Treat Population
Characteristics of the
Manesh et al. NEJM 2011 365: 883-891
* The CHADS2 risk of stroke ranges from 1 – 6, with higher scores indicating an increased risk. Three patients (one in the rivaroxaban group and two in the warfarin group) had a CHADS2 score of 1.
Characteristics of the
Intention-to-Treat Population at Baseline cont…
* The CHADS2 risk of stroke ranges from 1 – 6, with higher scores indicating an increased risk. Three patients (one in the rivaroxaban group and two in the warfarin group) had a CHADS2 score of 1.
Manesh et al. NEJM 2011 365: 883-891
• Phase III randomized, double-blind trial
• Apixaban 5 mg bid vs warfarin for stroke prevention in 18,201 patients with AF and at least 1 additional risk factor for stroke
• Randomized to apixaban 5 mg bid (n = 9120) or warfarin (target INR 2.0-3.0) (n = 9081)
• Primary efficacy outcome – stroke or systemic embolism
• Primary safety outcome – major bleeding
Granger CB et al. N Engl J Med 2011 Aug 27. [Epub ahead of print]
ARISTOTLE
(n=9081)
Age, years, median (25th, 75th %ile) 70 (63, 76) 70 (63, 76)
Women, % 35 35
1, % 34 34
2, % 36 36
≥ 3, % 30 30
Granger CB et al. N Engl J Med 2011 Aug 27. [Epub ahead of print] Duke Clinical Research Institute and Uppsala Clinical Research Center
Characteristic Apixaban
(n=9120)
Prior stroke, TIA or SE 19 20
Heart failure or reduced LV EF 35 36
Diabetes 25 25
Hypertension 87 88
Severe impairment (≤ 30) 1.5 1.5
Granger CB et al. N Engl J Med 2011 Aug 27. [Epub ahead of print]
Duke Clinical Research Institute and Uppsala Clinical Research Center
Baseline Characteristics
Primary Outcome
No. at Risk
Apixaban 9120 8726 8440 6051 3464 1754
Warfarin 9081 8620 8301 5972 3405 1768 Granger CB et al. N Engl J Me 2011 Aug 27. [Epub ahead of print]
Duke Clinical Research Institute and Uppsala Clinical Research Center
Efficacy Outcomes
(%/yr)
Stroke or systemic embolism* 1.27 1.60 0.79 (0.66, 0.95) 0.011
Stroke 1.19 1.51 0.79 (0.65, 0.95) 0.012
Ischemic or uncertain 0.97 1.05 0.92 (0.74, 1.13) 0.42
Hemorrhagic 0.24 0.47 0.51 (0.35, 0.75) <0.001
Systemic embolism (SE) 0.09 0.10 0.87 (0.44, 1.75) 0.70
All-cause death* 3.52 3.94 0.89 (0.80, 0.998) 0.047
Stroke, SE,or all-cause death 4.49 5.04 0.89 (0.81, 0.98) 0.019
Myocardial infarction 0.53 0.61 0.88 (0.66, 1.17) 0.37
* Part of equential testing sequence preserving the overall type I error
Major Bleeding
ISTH definition
No. at Risk Apixaban 9088 8103 7564 5365 3048 1515 Warfarin 9052 7910 7335 5196 2956 1491
Bleeding Outcomes
(%/yr)
Intracranial 0.33 0.80 0.42 (0.30, 0.58) <0.001
Gastrointestinal 0.76 0.86 0.89 (0.70, 1.15) 0.37
Major or clinically relevant
GUSTO severe bleeding 0.52 1.13 0.46 (0.35, 0.60) <0.001
TIMI major bleeding 0.96 1.69 0.57 (0.46, 0.70) <0.001
Any bleeding 18.1 25.8 0.71 (0.68, 0.75) <0.001
* Part of sequential testing sequence preserving the overall type I error
Conclusions
Treatment with apixaban as compared to warfarin in patients
with AF and at least one additional risk factor for stroke:
• Reduces stroke and systemic embolism by 21% (p=0.01)
• Reduces major bleeding by 31% (p<0.001)
• Reduces mortality by 11% (p=0.047)
with consistent effects across all major subgroups and with
fewer study drug discontinuations on apixaban than on warfarin,
consistent with good tolerability.
Summary of Clinical Trials
Dabigatran 150 mg BID
Rivaroxaban 20 mg HS
Apixaban 5 mg BID
Mortality

Stroke or Systemic Embolism
Connolly S et al NEJM 2009; Patel M et al NEJM 2011; Granger CB et al NEJM 2011
New Anticoagulant Therapies
Compared to Warfarin
Major Bleeding
All-cause Mortality
Intracranial Hemorrhage
Conclusion
• Compared to warfarin, the novel oral anticoagulants are at least as good at preventing stroke, have half the rate of ICH, appear to have 10% lower mortality and are easier to use
• But many practical issues are important in their safe use, including
– Adjusting for renal dysfunction
– Understanding how to manage procedures
– Understanding how to manage bleeding
– Avoiding aspirin without clear indication
• Having protocols in place to guide rationale use of the novel drugs is a high priority
Case 2
PMH
metoprolol and dabigatran
VS: BP 134/68, HR 78 irreg irreg
CV: irregularly irregular, no murmurs
ECG: atrial fibrillation with controlled VR
BUN/Cr – 34/1.2 (estimated creatinine clearance = 70)
Physical Exam
In preparation for surgery, you should:
a) Admit the patient to the hospital, stop dabigatran and administer IV heparin until the morning of surgery
b) Stop dabigatran 7 days prior to surgery and check INR on the morning of surgery
c) Stop dabigatran 2 days prior to surgery and check aPTT on the morning of surgery
Question
Copyright American Heart Association Weitz J I et al. Circulation 2012;126:2428-2432
Average Time Course for Effects of Dabigatran on
Activated Partial Thromboplastin Time (aPTT), Following
Dabigatran Dosing Regimens in Patients with Normal
Renal Function and Various Degrees of Renal Impairment
Pharmacokinetics of Dabigatran
• Disappearance curve of drug depends upon Cr Cl
– Disappearance of drug can be followed by aPTT
– When Cr Cl > 80 ml/min drug effect mostly gone at 24 hours with 150 mg dose as reflected by PTT
– When Cr Cl<30 ml/min drug effect about 50% at 48 hours at 75mg dose
• Time for discontinuation depends upon bleeding risk of surgery
• Can be dialysed with removal of 60% of drug in 2-3 hours
• No specific antidote
Weitz J I et al. Circulation 2012;126:2428-2432 Copyright © American Heart Association
Proposed Algorithm for Periprocedural Management of
Dabigatran
Bridging Algorithm for New Oral Anticoagulants
Now let’s assume that the patient is taking warfarin instead of dabigatran…
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
Question
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
Adverse Events Caused or Prevented by Intravenous Heparin
Kearon C, Hirsh J. N Engl J Med 1997;336:1506-1511.
Outcomes of Temporary
Warfarin (n=2,528)
Death 0% (0) 0.04% (1) NA
MI 0.2% (5) 0.1% (3) 0.32
Major or CRNM Bleeding
Minimal Bleeding 0.3% (6) 0.4% (10) 0.55
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
Copyright © American Heart Association Gallego P et al. Circulation 2012;126:1573-1576
Bridging Algorithm for Vitamin K Antagonists
Case 2 Teaching Points Dabigatran
• With normal kidney function, omit 2-3 doses for low risk surgery and 4-5 doses for higher risk surgery
• With GFR 30-50, omit for 1.5-2 days (3-4 doses) for low risk surgery
• With GFR <30, omit for 3-4 days (6-8 doses) for higher risk surgery
Case 2 Teaching Points Warfarin
• 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
National Averages
• 319,419 patients with non- valvular AF documented in most recently available 12 months
• 60.4% performance on anticoagulation for AF patients
• 16.9% performance for TE risk factor assessment
Overall representation
US Population Density
Question 6 - Post Test Question
Given the following patient characteristics, in which setting would switching from warfarin to dabigatran, rivaroxaban or apixaban be appropriate and supported by clinical data?
a) Ejection fraction of 30% with Class II heart failure
b) Normal functioning mechanical MVR
c) LVH with EF 55%; chronic renal insufficiency with creatinine clearance 10 ml/min
Question 6 (Cont.)
The RE-LY trial showed that: • dabigatran 150 mg BID was superior to warfarin in terms of
embolic events • dabigatran 110 mg BID dose was superior to warfarin in
terms of major bleeding
The Rocket-AF trial showed that: • rivaroxaban was non-inferior to warfarin by intention-to-
treat and superior by on treatment analysis in preventing embolic events
• bleeding risk was similar
ARISTOTLE showed that: • apixaban was superior to warfarin in preventing embolic
events with a reduced bleeding risk
Rationale
Rationale
ANSWER A: Ejection fraction of 30% with Class II heart failure is the correct answer
− Patients in the three trials included those with a low ejection fraction and heart failure
− Patients with a mechanical MVR were excluded and thus efficacy of novel anti-coagulants is not known in these patients
− Patients with a creatinine clearance of 10 ml/min should not have these drugs since they are excreted by the kidney
− Patients with liver dysfunction and an elevated prothrombin time should not be given these agents due to high risk of bleeding
References:
Patients With Atrial Fibrillation (Update on Dabigatran): A Report of
the American College of Cardiology Foundation Foundation/American
Heart Association Task Force on Practice Guidelines J Am Coll Cardiol,
2011; 57:1330-1337
2. Connolly SJ, Ezekowitz, MD, Yusuf S, et al. Dabigatran versus
warfarin in patients with atrial fibrillation N Engl J Med
2009;361:1139-1151
Palpitations
• Patient cardioverted to NSR after TEE demonstrated no thrombus
• Started on warfarin, switched from amlodipine to metoprolol for BP control and AF suppression
Noted to Have AF with Rapid Rate
• Cardioverted and begun on Sotalol 80 mg q/12
• Metoprolol stopped, Amlodipine restarted
• One month f/u admitted with recurrent atrial fibrillation and in retrospect complains of severe fatigue
• After weighing options, patient underwent Pulmonary Vein Isolation for atrial fibrillation
• Remained on Sotalol for 2 months which was then stopped
• He returns to your office and wishes to be taken off warfarin
3 Months Later, Patients with Rapid AF
a) Do a 24 hr Holter and if negative for atrial fibrillation stop warfarin
b) Do a 2 week ambulatory telemetry monitor and if negative stop warfarin
c) Urge him strongly to continue warfarin
d) Substitute newer agent
What would you do?
AFFIRM Investigators. N Engl J Med. 2002;347:1825-1833.
*Atrial Fibrillation Follow-up Investigation of Rhythm Management
44%
28%
43%
0
20
40
60
80
100
The RACE* Study: Increased Thromboembolic Events After Discontinuation of Anticoagulation
Van Gelder et al. N Engl J Med. 2002;347:1834-1840. * Rate Control Versus Electrical Cardioversion for Persistent Atrial Fibrillation
P5d
6 patients had events after cessation of warfarin
5 of these patients were in sinus rhythm
23/35 (66%) had events while taking warfarin with
INR <2
• Discontinuation of warfarin is potentially hazardous in such patients since they may be minimally symptomatic or asymptomatic and remain at risk of stroke
• Echo – normal
• Not hypertensive, diabetic, pft’s normal
• Discharged with ambulatory cardiac telemetry device
• Noted to have multiple episodes of asymptomatic atrial fibrillation up to 4 hours in duration
• Atrial fibrillation burden 20% of monitoring period
3 Years Ago Presented with TIA
Noted to Be in NSR
a) Initiate a rhythm control drug
b) Discharge on beta-blocker alone
What would you do?
What would you do?
Question
In reviewing INR’s – they vary widely and she complains that
blood tests are inconvenient and generally shows up once a
month for INR’s
What would you do?
b) Recommend a point of service monitor
c) Stop A/C since she had no current TIA’s
d) Consider dabigatran, rivaroxaban or apixaban
Question
What do you think the barriers are to regular INR testing?
a) Fear of testing
What Do You Think the Barriers Are to Regular INR
Testing?
Use of an Internet-Based Patient Self-Testing System
Ryan F, et al. J Thromb Haemost. 2009;7:1284-90.
• 24 Hour Holter Monitor is hardly adequate to assure she’s free of AF
• AF was asymptomatic to begin with
• Rhythm control drug doesn’t assure stroke risk has been eliminated nor does the lack of recurrent TIAs

mind the gap: af and evolving strategies in anticoagulation

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