I have nothing to disclose. Cara N. Pellegrini, MD Nothing to - - PowerPoint PPT Presentation

6/20/2016 1

I have nothing to disclose.

Cara N. Pellegrini, MD

Nothing to disclose

Discussion topics

• In 2016, how does one choose the right drug for

stroke prevention in AF?

• What about non-pharmacologic stroke prevention?
• What is the role of using antiarrhythmic drugs to

facilitate cardioversion and maintain sinus rhythm?

• When should you refer your patient for consideration
• f AF ablation, and how can you predict success?
• Should we be advocating lifestyle changes for AF?

Case #1

RS is an 78 yo M with persistent AF, h/o HTN, mild LV dysfunction, anemia, and gout. Which stroke prevention strategy would you suggest?

• A. Aspirin
• B. Warfarin
• C. Dabigatran
• D. Rivaroxaban
• E. Apixaban
• F. Aspirin and Clopidogrel

Aspirin Warfarin Dabigatran Rivaroxaban Apixaban Aspirin and Clopidogrel

10% 31% 10% 24% 10% 14%

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CHA2DS2-VASc Score

Risk factor Score Congestive heart failure / LV dysfunction 1 Hypertension 1 Age ≥ 75 2 Diabetes mellitus 1 Stroke / TIA / thrombo-embolism 2 Vascular disease 1 Age 65-74 1 Female 1

CHA2DS2-VASc Score 4

Annual Risk of Stroke or Systemic Embolism

10-year follow-up rates among 73,538 of “real world” patients in the Danish National Patient Registry who have nonvalvular AF and were not treated with warfarin.

Olesen JB and colleagues, BMJ 2011

HAS-BLED Score

Risk factor Score Uncontrolled hypertension 1 Significant renal dysfunction 1 Significant liver disease 1 Previous stroke 1 History of / predisposition to bleeding 1 Labile INRs 1 Age > 65 1 Antiplatelet / NSAID use 1 ≥ 8 alcoholic drinks / week 1

HAS-BLED Score 2

Major bleeding: bleeding requiring hospitalizaon, causing ↓ hemoglobin > 2 g/L, requiring transfusion.

Annual Risk (%/yr) of Major Bleeding

Olesen JB and colleagues, BMJ 2011

6/20/2016 3 Relative Risk of Stroke or Systemic Embolism Associated with Oral Anticoagulants and Antiplatelet Drugs

LaHaye SA and colleagues, European Heart Journal 2012

Relative Risk of Major Bleeding Associated with Oral Anticoagulants and Antiplatelet Drugs

LaHaye SA and colleagues, European Heart Journal 2012

Treatment Recommendation (Lowest Attributable Net Risk)

LaHaye SA and colleagues, European Heart Journal 2012

Validation table for CHA2DS2 VASc Score = 4, HAS-BLED score = 2

LaHaye SA and colleagues, European Heart Journal 2012

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Meta-Analysis of NOAC RCTs

Ruff CT and colleagues, The Lancet 2014

Stroke or systemic embolism Major bleeding

Meta-Analysis of NOAC RCTs

Ruff CT and colleagues, The Lancet 2014

Secondary efficacy and safety outcomes

Subgroup Analysis

Ruff CT and colleagues, The Lancet 2014

Subgroup Analysis

Ruff CT and colleagues, The Lancet 2014

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Recommendations for Pharmacologic Stroke Prevention

• Aspirin (low efficacy)
• Warfarin (low cost)
• Dabigatran (lowest stroke risk)
• Rivaroxaban (once daily dosing)
• Edoxaban (once daily dosing, CrCl ≤ 95 ml/min)
• Apixaban (lowest net risk)
• Aspirin + Clopidogrel (modest efficacy, high bleeding

risk) Interactions with medications, diet, patient preferences, monitoring requirements, renal failure

Resources

• AF clinical decision aid:

– http://www.afib.ca/

• Mobile app:

– Afib CDA – http://SPARCtool.com/

• American College of Cardiology

– http://www.teamanticoag.com/

Phone/iPad app: Afib CDA

$4.99

*Not in your handout

Phone app: SPARCtool.com

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Phone app: SPARCtool.com

Case #2

MF is an 80 yo M with PAF who has a h/o HTN, DM, a TIA, and PUD s/p GIB while on warfarin. How can his risk of subsequent thromboembolic event best be minimized?

• A. Warfarin plus PPI
• B. Apixaban
• C. Aspirin and clopidogrel
• D. Intervention on the left

atrial appendage

W a r f a r i n p l u s P P I A p i x a b a n A s p i r i n a n d c l

• p

i d

• g

r e l I n t e r v e n t i

• n
• n

t h e l e f t a . . .

10% 61% 2% 27%

Watchman

• Self-expanding nitinol frame covered by fabric
• Short-term anticoagulation recommended
• Now FDA approved!

Jain AK and colleagues, Heart 2011

Watchman Data

• 2 RCTs (1261 pts) + 2 registries (1145 pts)
• Non-inferior to warfarin (mostly)
• Provider experience important

– Complication rate: 7.7% -> 2.2%

• 99% off warfarin within a year
• NOAC comparisons not yet done

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Meta-Analysis: Watchman vs. Warfarin

Decreased:

• Hemorrhagic strokes

Increased:

• Ischemic strokes

No difference in all stroke or systemic embolism

Meta-Analysis: Watchman vs. Warfarin

Decreased:

• CV / unexplained death

Trend toward decrease in all-cause death

Meta-Analysis: Watchman vs. Warfarin

Decreased:

• Nonprocedural bleeding

Increased:

• Procedural bleeding

No difference in major bleeding

Meta-Analysis: Watchman vs. Warfarin

Decreased:

• Hemorrhagic strokes
• CV / unexplained death
• Nonprocedural bleeding

Increased:

• Ischemic strokes
• Procedural bleeding

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Amplatzer cardiac plug (ACP)

Jain AK and colleagues, Heart 2011 Urena M and colleagues, JACC 2013

• Nitinol only, barbs to increase stability
• High deployment success
• Low stroke/embolism rate
• 16% peri-device leak at 6 mo f/u
• No real trial data
• Not approved in US; approved in Europe

LARIAT snare

• Percutaneous

ligation of LAA

• Limited short-term

results favorable

• Painful
• Complicated
• Risky?
• Available in the US

via 510(K) approval process

Chatterjee S and colleagues, Ann Thorac Surg 2011

Thoracoscopic stand-alone left atrial appendectomy

Ohtsuka T and colleagues, JACC 2013

• Well-established as

part of cardiac surgery

• Very limited data on

stand-alone procedure

• Surgery!

True anticoagulation alternative?

• 150 pt Watchman (ASAP)

60 pt Amplatzer study

– Both non-randomized – Off anticoagulation – Lower than predicted stroke / embolism rates – 4% thrombus formation on Watchman (can occur late)

• Non-appendage clot sites
• Hybrid approach: low-

dose NOAC + Watchman?

Reddy VY and colleagues, JACC 2013 Wiebe J and colleagues, Catheter Cardiovasc Interv 2014 Perk G and colleagues, Eur Heart J Cardiovasc Imaging 2011

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Recommendation

• European Society of Cardiology: weak

recommendation for those with high stroke risk and contraindication to long-term anticoagulation

• Not yet part of US guidelines
• FDA: “suitable for warfarin” + “appropriate

reason to seek a non-drug alternative”

Case #3

MJ has h/o HTN and PAF x 1 year. Now for the first time she has not converted spontaneously. Which meds should she be given with CV?

• A. Anticoagulant only
• B. Anticoagulant and AVN blocker
• C. Anticoagulant, Flecainide, and

AVN blocker

• D. Anticoagulant and Amiodarone

A n t i c

• a

g u l a n t

• n

l y A n t i c

• a

g u l a n t a n d A V N . . . A n t i c

• a

g u l a n t , F l e c a i n i d e . . . A n t i c

• a

g u l a n t a n d A m i

• .

. .

15% 44% 18% 23%

Antiarrhythmic Treatment Prior to CV

• Enhance ability to cardiovert
• Avoid need for electrical cardioversion

– No sedation – No scheduling – Same need for anticoagulation

• Minimize risk of early recurrence
• Establish medication tolerability

Pharmacologic cardioversion

• One week or less of AF

– Dofetilide / Ibutilide – Flecainide / Propafenone – +/- Amiodarone

• > 1 week of AF

– Dofetilide – +/- Ibutilide, Amiodarone

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Antiarrhythmic maintenance AAD use

>1 AF episode Meds possible Symptoms

• r poor

rate control Long-term sinus possible

Calkins H and colleagues, Circ Arrhythm Electrophysiol 2009

Meta-Analysis of Efficacy of AADs

52% with no AF (95% CI: 47-57%) average f/u = 1 yr

Placebo = 25% efficacy (95% CI: 15-34%)

Differential drug effectiveness

(SAFE-T – persistent AF pts)

• Spontaneous conversion:

~ 25% (drugs) vs < 1% (placebo)

• Failure of CV: ~ 25%

(drugs) vs 33% (placebo)

• Amiodarone 6x more

effective than Sotalol

• Both best placebo

Singh BH and colleagues, NEJM 2005

Time to AF recurrence after CV

Guideline Recommendations

January CT and colleagues, JACC 2014

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My Recommendations

January CT and colleagues, JACC 2014

Case #4

GG is a 60 yo F with PAF and HTN who has episodes despite treatment with metoprolol. Why should she consider AF ablation?

• A. Decrease AF symptomatic

burden

• B. Minimize stroke risk
• C. Decrease likelihood of

developing HF

• D. Improve her survival

Decrease AF symptomat.. Minimize stroke risk Decrease likelihood of d... Improve her survival

28% 25% 14% 33%

Reasons for AF ablation

• Improvement of QOL
• ?Decreased stroke risk
• ?Decreased heart failure risk
• ?Improved survival

AF ablation

Calkins H and colleagues, Heart Rhythm 2012

Goal = Elimination of triggers and alteration

• f substrate

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Meta-Analysis of AF Ablation Efficacy

Calkins H and colleagues, Circ Arrhythm Electrophysiol 2009

57% 71% 72% 77% 26%

1 No AAD >1 No AAD 1 + AAD >1 + AAD Repeat

Outcomes - PAF

AF ablation Medications

~60-75% efficacy 52% efficacy 5% complication rate 30% adverse events Meta-analysis of RCTs only: 77.8% efficacy 23.3% efficacy

Bonanno C and colleagues, J Cardiovasc Med 2010 Calkins H and colleagues, Circ Arrhythm Electrophysiol 2009

Ablaon ≠ Cure

Single procedure success Multiple procedure success Weerasooriya and colleagues, JACC 2011

Persistent AF

Verma A and colleagues, NEJM 2015

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Vicious Cycle

Maisel and Stevenson, Am J Cardiol 2003

AF and Heart Failure: ARC-HF

LVEF ∆Peak VO2 HF symptoms

Ablation Ablation Ablation Rate Control Rate Control Rate Control

Jones et al, JACC 2013

Jones and colleauges, JACC 2013

AF and Heart Failure: AATAC-AF

70% Arrhythmia free in Ablation Group 34% Arrhythmia free with Amiodarone 10% discontinuation

DiBiase L and colleagues, Circulation 2016

Left atrial fibrosis predicts outcome

Higuchi K and colleagues, Heart 2014

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Personalized Ablation Approach

Rotors Surgical CFAE Ganglionated Plexi Triggers

Prophylactic PVI

Steinberg J and colleagues, Heart Rhythm 2014

AFL and AF ablation AFL ablation only AFL ablation only AFL and AF ablation

Freedom from AF AF burden

HRS Guidelines for AF Ablation

• Symptomatic AF, refractory or intolerant to at

least one antiarrhythmic medication

– PAF: recommended (I A) – Persistent: reasonable/may be considered (IIa/b B)

• Prior to initiation of antiarrhythmic

– PAF: reasonable (IIa B) – Persistent: may be considered (IIb C)

January CT and colleagues, JACC 2014

Recommendations

• Ablaon ≠ cure
• Prepare for > 1 procedure, risk of complication
• Ablation does improve QOL, maybe more
• Ablation outperforms medications
• Potentially big benefit in heart failure
• Personalized approach
• Please refer, early

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Case #5

PH has paroxysmal AF, but he isn’t interested in an invasive procedure. What, if anything, can he do to minimize his AF burden?

• A. Exercise as much as possible
• B. Lose weight, control his blood

pressure, treat his sleep apnea

• C. Give up coffee
• D. A, B, and C
• E. There is no data that lifestyle

changes reduce AF

E x e r c i s e a s m u c h a s p

• s

s i b l e L

• s

e w e i g h t , c

• n

t r

• l

h i s . . . G i v e u p c

• f

f e e A , B , a n d C T h e r e i s n

• d

a t a t h a t l i f e s . . .

2% 25% 15% 58% 0%

Abnormal atrial substrate in lone AF

Teh A and colleagues, Heart Rhythm 2012

Control pt AF pt baseline AF pt ≥ 6 mo f/u

RCT of weight reduction + RFM on AF

Abed HS and colleagues, JAMA 2013 AF on Holter Decreased Intervention group: 60% -> 20% Control group: 60% -> 50% Pathak RK and colleagues, JACC 2014

ARREST-AF Cohort Study

BP, Weight, Lipids, Sugars, OSA, Smoking, Alcohol

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ARREST-AF Cohort Study

Pathak RK and colleagues, JACC 2014

Patient Survey 7-day monitors, ECGs, symptoms Intervention group Control group

Response to AF ablation worse in metabolic syndrome and OSA patients

Mohanty S and colleagues, J Cardiovasc Electrophysiol 2014 52% 40% 38% 29%

AF recurrence-free survival

Improvement with lifestyle change

Mohanty S and colleagues, J Cardiovasc Electrophysiol 2014

RCT of Exercise in PAF

Malmo V and colleagues, Circulation 2016

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RCT of Exercise in PAF

Malmo V and colleagues, Circulation 2016

Caffeine = good for AF?

Cheng M and colleagues, Can J Cardiol 2014

Recommendations

• Get your patients to give up all the good stuff!
• If anyone has interest in partnering to set up a

multi-disciplinary CV risk reduction program here, please talk to me.

Summary

• Weigh calculated stroke risk and bleeding risk in

choosing anticoagulation strategy

• Non-pharmacologic stroke reduction options

exist; may be applicable in selected patients

• CV most new persistent AF patients
• AADs if symptomatic and repeated AF
• Ablaon ≠ cure; ablaon = best outcomes;

moving earlier in algorithm

• Addition of lifestyle change may equal / extend

positive effects of ablation

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Thank you!