Updates in AF Cara Pellegrini, MD Acting Chief of Cardiology, SFVA - - PDF document

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Updates in AF Cara Pellegrini, MD Acting Chief of Cardiology, SFVA - - PDF document

Feb 13, 2023 43 likes •224 views

Speaker disclosure Abbott consultant (minor) Updates in AF Cara Pellegrini, MD Acting Chief of Cardiology, SFVA Associate Professor of Medicine, UCSF May 22, 2017 Discussion topics Case #1 RS is an 78 yo M with new persistent AF, h/o

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SLIDE 1

Updates in AF

May 22, 2017

Cara Pellegrini, MD

Acting Chief of Cardiology, SFVA Associate Professor of Medicine, UCSF

Speaker disclosure

§ Abbott – consultant (minor)

Discussion topics

§How does one choose the right drug for stroke prevention in AF? §How worried should I be about availability of reversal agents §What about non-pharmacologic stroke prevention? §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 new persistent AF, h/o HTN, mild LV dysfunction, PVD, anemia, and gout. Which stroke prevention strategy would you suggest?

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

F. Edoxaban

  • G. Aspirin and Clopidogrel
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SLIDE 2

Case #1

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

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

F. Edoxaban

  • G. Aspirin and Clopidogrel

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

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SLIDE 3

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

Annual Risk (%/yr) of Major Bleeding

Olesen JB and colleagues, BMJ 2011

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

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SLIDE 4

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

LaHaye SA and colleagues, European Heart Journal 2012

Phone apps: Afib CDA + SPARCtool.com

Phone app: SPARCtool.com Meta-Analysis of NOAC RCTs

Ruff CT and colleagues, The Lancet 2014

Stroke or systemic embolism Major bleeding

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SLIDE 5

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

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

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SLIDE 6

Resources

§Online AF clinical decision aid:

  • http://www.afib.ca/

§Mobile apps:

  • AFib CDA
  • http://SPARCtool.com/

§American College of Cardiology

  • http://www.teamanticoag.com/

Case #2

HW is a 67 yo F with HTN and new paroxysmal AF. She is very concerned about potential bleeding and the need for a reversal agent. Which agent has the worst

  • utcome if bleeding occurs?
  • A. Warfarin
  • B. Dabigatran
  • C. Rivaroxaban
  • D. Apixaban
  • E. Edoxaban

Case #2

HW is a 67 yo F with HTN and new paroxysmal AF. She is very concerned about potential bleeding and the need for a reversal agent. Which agent has the worst

  • utcome if bleeding occurs?
  • A. Warfarin
  • B. Dabigatran
  • C. Rivaroxaban
  • D. Apixaban
  • E. Edoxaban

Observation outcomes after major bleeding

Warfarin DOAC Time following index hospitalization (days)

In-hospital mortality significantly lower following DOAC bleeding: 9.8% vs 15.2 % 30 day mortality trended lower: 12.6% vs. 16.3%

Xu Y and colleagues, Chest 2017

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SLIDE 7

Causes of Death in AF

Gómez-Outes A and colleagues, JACC 2016 Dabigatran (Pradaxa) Rivaroxaban (Xarelto) Apixaban (Eliquis) Edoxaban (Savaysa) Drug class Direct thrombin inhibitor Factor Xa inhibitor Factor Xa inhibitor Factor Xa inhibitor Efficacy vs. warfarin Superior Non-inferior Superior Non-inferior Major bleeding

  • vs. warfarin

Similar Similar Reduced Reduced Reversal agents Idarucizumab (Praxbind), ciraparantag Andexanet alfa, ciraparantag Andexanet alfa, ciraparantag Andexanet alfa, ciraparantag Elimination half- life (hrs) 12-17 5-9 young 11-13 elderly 12 10-14 Renal dosing Avoid CrCl < 15

  • r HD

Avoid CrCl < 15

  • r HD

Approved for HD patients Avoid CrCl > 95, < 15, HD Hepatic dose adjustments OK in liver disease Avoid in Child- Pugh B Avoid in Child- Pugh C Avoid in Child- Pugh B Avoid combo / decrease dose* Dronedarone* Phenytoin Phenytoin

Declining stroke risk after AF episode

Turakhia MP and colleagues, Circ Arrhythm Electrophysiol 2015

Declining stroke risk after AF episode

Turakhia MP and colleagues, Circ Arrhythm Electrophysiol 2015

  • 83% no AF in 120 days

prior to stroke

  • Almost 25% had h/o AF,

but no AF pre-stroke

  • > Poor Sensitivity
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SLIDE 8

Future Directions: Targeted Therapy

  • Prn anti-coagulation
  • Guided by actual

arrhythmia burden

Passman R and colleagues, J Cardiovasc Electrophysiol 2016

Case #3

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

Case #3

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

Watchman

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

Jain AK and colleagues, Heart 2011

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SLIDE 9

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

Meta-Analysis: Watchman vs. Warfarin

Decreased: §Hemorrhagic strokes Increased: §Ischemic strokes

No difference in all stroke or systemic embolism

Holmes DR and colleagues, JACC 2015

Meta-Analysis: Watchman vs. Warfarin

Decreased: §CV / unexplained death

Trend toward decrease in all-cause death

Holmes DR and colleagues, JACC 2015

Meta-Analysis: Watchman vs. Warfarin

Decreased: §Nonprocedural bleeding Increased: §Procedural bleeding

No difference in major bleeding

Holmes DR and colleagues, JACC 2015

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SLIDE 10

Meta-Analysis: Watchman vs. Warfarin

Decreased: §Hemorrhagic strokes §CV / unexplained death §Nonprocedural bleeding Increased: §Ischemic strokes §Procedural bleeding

Holmes DR and colleagues, JACC 2015

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
  • f cardiac surgery
  • Very limited data on

stand-alone procedure

  • Surgery!
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SLIDE 11

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 et al, JACC 2013; Wiebe J et al, Catheter Cardiovasc Interv 2014 Perk G et al, Eur Heart J Cardiovasc Imaging 2011

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 #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

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 hers survival

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SLIDE 12

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

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

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SLIDE 13

Ablation ≠ Cure

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

Persistent AF

Verma A and colleagues, NEJM 2015

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 colleagues, JACC 2013

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SLIDE 14

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

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

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SLIDE 15

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

§ Ablation ≠ 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

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

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
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SLIDE 16

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

ARREST-AF Cohort Study

Pathak RK and colleagues, JACC 2014

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

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SLIDE 17

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

RCT of Exercise in PAF

Malmo V and colleagues, Circulation 2016

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SLIDE 18

Caffeine = good for AF?

Cheng M et al, Can J Cardiol 2014

Recommendations

§ Get your patients to give up all the good stuff! § Consider a multi-disciplinary CV risk reduction program

Summary

§ Weigh calculated stroke risk and bleeding risk in choosing anticoagulation strategy § Don’t be overconcerned with reversal agent status § Non-pharmacologic stroke reduction options exist; may be applicable in selected patients § Ablation ≠ cure; ablation = best outcomes; moving earlier in algorithm § Addition of lifestyle change may equal / extend positive effects of ablation

Thank you!