5/20/2015 1 Are You Up-to-Date in Your Management of Atrial Fibrillation? Greg Flaker MD Professor of Medicine University of Missouri Wes and Simon Sorenson Chair of Cardiovascular Research June 2015 Consulting agreement • Pfizer • Daiichi Sankyo • Bristol-Myers Squibb • Janssen Pharmaceuticals Disclosures Time Course and Management of AF European Heart J 2010;31:2369-2429 Treatment Control RR Study n/N n/N (95% CI Random) 01 Heart Failure Van Den Berg 2/7 7/11 ● SOLVD 10/186 45/188 ● ValHeFT 116/2209 173/2200 ● Charm 179/2769 216/2749 ● Subtotal (95%CI) 307/5171 441/5148 02 Hypertension CAPP 117/5492 135/5493 ● LIFE 179/4417 252/4387 ● STOPH2 200/2205 357/4409 ● Subtotal (95%CI) 496/12114 744/1289 03 Atrial Fibrillation Madrid 9/79 22/75 ● Ueng 18/70 32/75 ● Subtotal (95%CI) 27/149 54/150 04 Post-Myocardial Infarction TRACE 22/790 42/787 ● GISSI 665/8865 721/9633 ● Subtotal (95%CI) 687/9655 763/9633 Total (95%CI) 1517/27089 2002/29220 -1 -2 1 5 10 ● ● ● ● ● Prevention of AF with ACEi/ ARB’s JACC 2005;45:1832-1839 Atorvastatin and AF Heart Rhythm 2010;7(10):1475-81 MRI Findings in Lone AF
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5/20/2015
1
Are You Up-to-Date in Your Management of Atrial Fibrillation?
Greg Flaker MD Professor of Medicine University of Missouri
Wes and Simon Sorenson Chair of Cardiovascular Research
*TSOAC=Target-specific oral anticoagulant (Cove CL, Hylek EM. J Am Heart Assoc. 2013;Oct 23 ESC Guidelines: Camm AJ et al. Eur Heart J. 2012;33:2719-47. AHA/ACC/HRS Guidelines: January CT et al. Circulation, 2014
Anticoagulant, Antiplatelet, or Neither:
Current Guidelines
CHADS-VASc: How Many More AF Patients Will Receive Anticoagulation?
Swedish Registry Eur Heart J 2012;33:1431-3
AVERROES DESIGN
R
36 countries, 522 centres
AF and ≥ 1 risk factor,
demonstrated or
expected
unsuitable for VKA
APIXABAN 5mg BID 2.5 mg BID in selected patients
5,600 patients
ASA (81-324 mg/d)
Double-Blind
Primary Outcome: Stroke or systemic embolism (intention to treat analysis)
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NEJM 2011; 364: 806-17
NOAC’s vs. Warfarin Efficacy and Safety in non-valvular AF*
* Hemodynamically significant MS, mechanical or biological prosthetic valve or repair
Silent AF 56 yo Catholic priest s/p MI and stroke • normal coronary arteries, LVEF 30% • carotid Duplex < 50% lesions bilaterally • normal hypercoagulable work-up • ICD implanted
N Engl J Med 2002;346(26):2066
Devices for AF: Living Better Electrically
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AF “burden”
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Sleep apnea and AF Subclinical AF and Risk of Stroke
NEJM 2012;366:120-9
How Much AF Is Needed to Put the Patient at Risk of Stroke?
93 yo white female hospitalized for TIA symptoms
• s/p MI and pacemaker
• history of hypertension
• Neurologist performs CT and echo, continues aspirin
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Cryptogenic Stroke and Underlying AF The Crystal-AF Study
22 NEJM 2014;370:2478-86
The Reveal LINQ ICM System The Complete Monitoring Solution
Mobile
Alerts
Streamlined Reports
Improved CareLink®
User Interface
Patient
Assistant
MyCareLink™
Patient Monitor
Simplified Insertion
Procedure
Reveal LINQ™ ICM
Wireless
Cellular
Bridging
80 yo white female with an end of life pacemaker. She has hypertension, a history of a stroke, and paroxysmal atrial fibrillation. She is treated with warfarin.
How do you manage warfarin in this high risk
patient prior to pulse generator replacement? 1. Hold warfarin, bridge with UFH or LMWH. 2. Hold warfarin, perform surgery when INR<1.5. 3. Replace device with a therapeutic INR.
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Bridge or Continue Coumadin for Device Surgery Randomized Trial
(Bruise Control) Warfarin arm
• Perform surgery with INR <3.0 <3.5 with one or more mechanical valves
Heparin arm
• LMWH stopped > 24 hours before surgery
Heparin stopped 4 hours before surgery
• Either restarted 24 hours after, continued until INR therapeutic
Bridging in ARISTOTLE Blood 2014;124(25):3692-3698
9250 interruptions for at least one invasive procedure
• Dental procedure 15%
• Colonoscopy 10%
• Cataract removal/opthalmology 9%
• Pacemaker/ICD 3.5%
• Cystoscopy 3%
• PCI 2.8%
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Bridging in ARISTOTLE Blood 2014;124(25):3692-3698
Agent Interruption UH/ LMWH
Major Bleeding
TE Event
apixaban 62.5% 11.7% 1.6% 0.4%
warfarin 62.5% 11.7% 1.9% 0.6%
Main conclusions 1) Interruption is common, often with no bridging (low risk
procedure, low risk for stroke?) 2) Low risk of stroke/SE; higher risk of major bleeding. Comparable
between apixaban and warfarin. 3) Low embolic rate and bleeding regardless of interruption or not.
Guidelines for LMWH Bridging
For patients at high risk of thrombotic events with high risk for surgical bleeding:
• Stop LMWH 24 hours (instead of 12 hours) prior to surgery
• Begin LMWH 48-72 hours after (instead of 24 hours) if high risk for bleeding
• Reduced dose LMWH for CrCl <30cc/min
CHEST Feb 2012;141(2 Suppl):e326S-e350S.
The elderly bleeding patient
85 yo white female with AF, s/p MI. On warfarin
(INR=2.5), she is admitted with a GI bleed. CHA2DS2-VASc = 4
Acute management: reversal agent? Long term management 1) no anticoagulation ever 2) restart warfarin, aim for a lower INR 3) use another agent a) aspirin b) dabigatran c) rivaroxaban d) apixaban 33
Anticoagulation reversal
Vitamin K • slow in action…24 hours
Fresh frozen plasma (FFA) • Volume….great for a volume depleted, bleeding patient
CV Death 2.65 (87) 2.3 (226) 1.2 (0.91-1.55) 0.2104
Non-CV Death 1.5 (49) 1.1 (109) 1.3 (0.88-1.82) 0.1964
MI 0.3 (10) 0.5 (51) 0.58 (0.27-1.25) 0.1646
Major Bleeding 2.4 (74) 2.1 (199) 1.15 (0.85-1.53) 0.3656
JACC in press
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JACC in press
Amiodarone for Atrial Fibrillation
JACC 2014;64:e1-76
Time Course and Management of AF
European Heart J 2010;31:2369-2429
Catheter Based PVI for AF
Success • Approximately 70% with 1 procedure • Up to 85% with a second procedure
Depends on 1) Paroxysmal vs permanent AF 2) Extent of post procedure monitoring 3) Co-morbid conditions (OSA)
RF Ablation vs Antiarrhythmic Drugs For Paroxysmal AF
RAAFT-2 Trial JAMA 2014;311(7):692-99
Editorial by Hugh Calkins: ablation is not curative
Major Complications with PV Ablation 1,049 patients, 7 series
Circulation 2005: 112;1214-31
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Time Course and Management of AF
European Heart J 2010;31:2369-2429
Everyone with AF deserves one CV.
Myths about Cardioversion
How Many Patients Undergo Cardioversion?
0%
20%
40%
60%
80%
100%
AFFIRM n=4060
2002
RE-LY n=18,113
2009
ARISTOTLE n=18,201
2011
ROCKET-AF n=14,264
2011
1600
553*
1270
285
Number of patients who underwent at least one cardioversion
AFFIRM Circ Arrhythmia and Electrophysiology 2011;4:465-69 RE-LY Circulation 2011;123:131-6
* electrical conversion only
ARISTOTLE JACC 2014 ;63:1082-7. ROCKET AF JACC 2013;61:1998-2006
If AF has lasted < 48 hours, it is OK to cardiovert without anticoagulation.
Myths about Cardioversion
Conversion of AF <48 hrs Prevention of stroke
AF< 48 hours • n= 3,143
• mean age 61 + 12.4
• mean CHADS =1
JACC 2013;62:1187-92
Conversion of AF <48 hrs Prevention of stroke
US Recommendation (JACC 2014;64(21):2246-80.
• high risk: begin anticoagulation (LMWH or UH, thrombin inhibitor or factor Xa inhibitor) as soon as possible before or after CV, followed by long term anticoagulation (class I)
• low risk: as above or consider no anticoagulation (class IIb)