Atrial Fibrillation Review and Update Cara Pellegrini, MD - - PowerPoint PPT Presentation

6/17/2019 1

Atrial Fibrillation Review and Update

Cara Pellegrini, MD

Associate Professor of Medicine, UCSF Director, Cardiac Electrophysiology, San Francisco VA Site Director, Cardiology and Cardiac EP Fellowship, SFVA

Disclosures

• Minor consultant – Abbott and Medronic

Newsworthy Topics of Discussion

• Stroke prevention
• DOAC preferred over warfarin for most
• Reversal agents available, for emergent situations
• Double over triple therapy after PCI/ACS for most
• Ablation
• CABANA – ablation and hard outcomes
• CASTLE-AF – ablation in HF patients
• Treatment of contributing factors
• Weight loss and CV risk factor modification can

reverse AF process

Mary is a 66 year-old overweight woman with hypertension and GERD who complained of

• palpitations. You ordered an event monitor and

diagnosed her with paroxysmal AF. Now you suggest she start taking…

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

A s p i r i n A p i x a b a n D a b i g a t r a n W a r f a r i n

11% 0% 17% 72%

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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 3

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 1

Meta-Analysis of DOAC RCTs

Ruff CT and colleagues, The Lancet 2014

Stroke or systemic embolism Major bleeding

Meta-Analysis of DOAC RCTs

Secondary efficacy and safety outcomes

Ruff CT and colleagues, The Lancet 2014

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Simplified DOAC Algorithm

CVA?

• Dabigatran

QD?

• Rivaroxaban

Most

• Apixaban

A couple years later Mary complains to you of dark, tarry stools. W/u confirms melena and anemia (Hgb 9). You immediately discontinue apixaban and give…

• A. Idarucizamab
• B. Andexenat alfa
• C. Prothrombin complex

concentrate (PCC)

• D. None of the above

I d a r u c i z a m a b A n d e x e n a t a l f a P r

• t

h r

• m

b i n c

• m

p l e x c

• .

. . N

• n

e

• f

t h e a b

• v

e

10% 67% 14% 10%

Causes of Death in AF

Gómez-Outes A and colleagues, JACC 2016

If you bleed, better to be on DOAC than warfarin

Reversal agents are here!

Burnett A, Siegal D, and Crowther M, BMJ 2017

Andexanet alfa Idarucizumab Ciraparantab

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REVERSE-AD (Idarucizamab)

Pollack CV Jr et al, NEJM 2017

Uncontrolled bleeding group

Diluted thrombin time

Urgent procedure group

ANNEXA-4 (andexanet alfa)

• Add data re efficacy and safety

Connolly SJ et al, NEJM 2019

% Excellent/Good Hemostatis

When to use reversal agent

Cuker et al, Am J Hematol 2019

Bleeding that is:

• life-threatening
• into critical organ
• uncontrollable
• related to DOAC

Procedure that is:

• Urgent
• Unable to be performed on DOAC
• In pt with relevant DOAC level

Reversal agent appropriate

Trauma Overdose Any bleeding/procedure

X X X

Mary recovers. 6 months later she presents to your

• ffice with chest pain and concerning ECG changes.

She ultimately undergoes PCI of 98% LAD lesion. In addition to clopidogrel, you now recommend…

• A. Apixaban alone
• B. Apixaban and aspirin
• C. Switch apixaban to warfarin
• D. Switch apixaban to warfarin and

aspirin

Apixaban alone Apixaban and aspirin Switch apixaban to warfarin Switch apixaban to warfar..

42% 4% 0% 54%

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AUGUSTUS – Apixaban alone is best in AF patients with recent ACS or PCI

Lopes RD et al, NEJM 2019

Major/relevant bleeding Major bleed Hospitalization Death or ischemic events

Caveats

• PIONEER AF-PCI (rivaroxaban) and RE-DUAL PCI

(dabigatran) Trials already showed lower bleeding

• Neither fully assessed impact of ASA
• Nonsignificant increase in coronary ischemic events
• Consistent with other AF+PCI DOAC trials
• Mean time index event -> randomization = 6.6 days
• Likely many received ASA during that time

New guideline recommendations

Class I recommendation to use DOAC over warfarin if DOAC-eligible for nonvalvular AF

Excludes only mod-sev mitral stenosis or mech valve

Class I recommendation for idarucizumab for dabigatran reversal for life-threatening bleeding or urgent procedure Class IIa recommendation for andexanat alfa for apixaban or rivaroxaban reversal for life-threatening or uncontrolled bleeding Class IIa recommendations for double instead of triple therapy after PCI for ACS if CHA2DS2-VASc ≥ 2

Warfarin, dabigatran, or rivaroxaban

January CT et al, Circulation / JACC / Heart Rhythm 2019 IIa IIa I I

Mary has now been cp-free for a year, but her palpitations are more frequent. Her neighbor had an AF ablation and Mary is wondering if she should too. You say…

• A. Oh yes, it can make you feel better +

live longer

• B. Yes, it’s the most effective symptomatic

therapy

• C. You can, but the AF will come back, it

always does

• D. I wouldn’t recommend it at your age

O h y e s , i t c a n m a k e y

• u

f e . . Y e s , i t ’ s t h e m

• s

t e f f e c t i v . . . Y

• u

c a n , b u t t h e A F w i l l . . . I w

• u

l d n ’ t r e c

• m

m e n d i t . . .

8% 4% 20% 68%

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CABANA

Total N = 2204 Ablation N = 1108 Meds N = 1096

Age 68 69 Female 37% 37% HTN 79% 82% Diabetes 25% 26% CHA2DS2-VASc (median) 3 3 Paroxysmal 42% 43% Rhythm control drug 82% 82%

Packer DL, et al, JAMA 2019

CABANA – Primary Outcome

Death, Disabling Stroke, Serious Bleeding, or Cardiac Arrest

Packer DL, et al, JAMA 2019

CABANA – Secondary Outcomes

Mortality or CV Hospitalization Freedom from AF

Packer DL, et al, JAMA 2019

CABANA – Per Protocol Analysis

Death, Disabling Stroke, Serious Bleeding, or Cardiac Arrest

Packer DL, et al, JAMA 2019

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Great deal of clarity…. My take homes from CABANA

• No evidence that AF ablation impacts mortality,

disabling CVA, serious bleeding, and cardiac arrest

• AF ablation did modestly reduce CV hospitalization
• AF ablation outperformed meds for AF reduction
• There was a lot of cross-over
• Lack of equipoise?
• Strongly positive per protocol analysis is hypothesis

generating, at most

• QOL improved significantly more in ablation group

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Mike is Mary’s 72 year-old husband, whom you manage for heart failure. After his Apple Watch noted irregular heart rhythms, an event monitor confirmed AF. He c/o

• fatigue. You suggest…
• A. AF ablation
• B. Amiodarone
• C. AVJ ablation and pacemaker
• D. HF management without directed

AF therapy

A F a b l a t i

• n

A m i

• d

a r

• n

e A V J a b l a t i

• n

a n d p a c e m a k e r H F m a n a g e m e n t w i t h

• u

t . . .

54% 23% 8% 15%

LVEF Change with AF ablation

Ganesan et al, Heart, Lung and Circulation 2015

Pooled = 13.3%

Meta-Analysis of 4 RCTs

LVEF Peak VO2 6 min walk QOL

Favors HR Control Favors Ablation Favors Ablation Favors HR Control

Al Halabi et al, JACC: Clin Electrophysiol 2015

Favors HR Control Favors Ablation Favors HR Control Favors Ablation

Pooled = 8.5%

AATAC-AF: Ablation vs. Amio

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

Di Biase et al, Circulation 2016

Better LVEF, QOL, HF hosp, + mortality too!

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CASTLE-AF

Total N = 363 Ablation Grp N = 179 Conventional Grp N = 184 Mean age (yrs) 64 64 Mean LVEF 32.5% 31.5% NYHA Class I/II 69% 72% Nonischemic 60% 48% Paroxysmal AF 35% 35% AAD use 32% 30%

Marrouche et al, NEJM 2018

CASTLE-AF: ablation reduces HF admissions and mortality

Marrouche et al, NEJM 2018

Risk Reduction: 38%

Significant reduction in both HF hosp + all-cause mortality

All-cause mortality HF Hospitalizations

Marrouche et al, NEJM 2018

AF burden decreased with ablation

Marrouche et al, NEJM 2018

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Significant interaction by LVEF

Marrouche et al, NEJM 2018

New guideline recommendation

Class IIb recommendation for AF ablation in selected patients with symptomatic AF and heart failure with a reduced EF to potentially lower mortality and reduce HF hospitalizations

January CT et al, Circulation / JACC / Heart Rhythm 2019 IIb

• Do not need complete resolution of AF
• burden reduced by half, but not gone (CASTLE-AF)
• Highly selected populations
• Benefit did not extend to those with LVEF < 25%

Mike had an ablation and is doing well. Mary is considering it, but asks you if there is anything else she could do that might reduce her AF burden and

• symptoms. You tell her…
• A. Yes! Weight loss could cure your AF
• B. Sort of. Exercise can improve symptoms,

but doesn’t actually change AF burden.

• C. No. Just have the ablation already.

Y e s ! W e i g h t l

• s

s c

• u

l d c u . . S

• r

t

• f

. E x e r c i s e c a n i m p . . . N

• .

J u s t h a v e t h e a b l a t i

• .

. .

38% 14% 48%

AF: result of occult atrial (and ventricular) cardiomyopathy?

Wijesurendra R et al, Circulation 2016

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Abnormal atrial substrate

Teh A and colleagues, Heart Rhythm 2012

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

A model from which to learn?

RCT of weight loss + RFM

Abed HS and colleagues, JAMA 2013

AF burden by Holter: Intervention: 60% -> 20% Controls: 60% -> 50% Symptom burden Waist circumference

Months Months

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

Dose effect of weight loss on AF

Pathak RK et al, JACC 2015

Weight fluctuation partially

• ffsets benefit

Pathak RK et al, JACC 2015

Weight loss can reverse clinical AF

Middeldorp ME et al, EP Europace 2018

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RCT of Exercise in PAF

Malmo V and colleagues, Circulation 2016

Weight loss, exercise and AF

Lavie CJ et al, JACC 2017

New guideline recommendation

Class I recommendation for weight loss and risk factor modification for overweight and obese AF patients

January CT et al, Circulation / JACC / Heart Rhythm 2019 I

• Can avoid need for ablation / AADs or improve
• utcomes in setting of ablation
• Dose response relationship, partially attenuated by

weight fluctuation Mary loses 20# and her palpitations go away. Mike continues to do well. Thanks to you!

6/17/2019 14

Conclusions

• Stroke prevention
• DOAC preferred over warfarin for most
• Reversal agents available, for emergent situations
• Double over triple therapy after PCI/ACS for most
• Ablation
• CABANA – ablation and hard outcomes
• CASTLE-AF – ablation in HF patients
• Treatment of contributing factors
• Weight loss and CV risk factor modification can

reverse AF process

Ready for lift off!