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

6/17/2019 Disclosures • Minor consultant – Abbott and Medronic 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 Mary is a 66 year-old overweight woman with Newsworthy Topics of Discussion hypertension and GERD who complained of palpitations. You ordered an event monitor and diagnosed her with paroxysmal AF. Now you suggest • Stroke prevention she start taking… • DOAC preferred over warfarin for most • Reversal agents available, for emergent situations • Double over triple therapy after PCI/ACS for most 72% A. Aspirin • Ablation B. Apixaban • CABANA – ablation and hard outcomes C. Dabigatran • CASTLE-AF – ablation in HF patients 17% • Treatment of contributing factors D. Warfarin 11% • Weight loss and CV risk factor modification can 0% reverse AF process n n n n r i a a r i i b r a p a t s a r f A x g a p i i b W A a D 1

6/17/2019 CHA 2 DS 2 -VASc Score HAS-BLED Score Risk factor Score Risk factor Score Congestive heart failure / LV dysfunction 1 Uncontrolled hypertension 1 Hypertension 1 Significant renal dysfunction 1 Age ≥ 75 2 Significant liver disease 1 Diabetes mellitus 1 Previous stroke 1 Stroke / TIA / thrombo-embolism 2 History of / predisposition to bleeding 1 Vascular disease 1 Labile INRs 1 Age 65-74 1 Age > 65 1 Female 1 Antiplatelet / NSAID use 1 ≥ 8 alcoholic drinks / week 1 CHA 2 DS 2 -VASc Score 3 HAS-BLED Score 1 Meta-Analysis of DOAC RCTs Meta-Analysis of DOAC RCTs Stroke or systemic embolism Secondary efficacy and safety outcomes Major bleeding Ruff CT and colleagues, The Lancet 2014 Ruff CT and colleagues, The Lancet 2014 2

6/17/2019 Simplified DOAC Algorithm 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… 67% CVA?  Dabigatran A. Idarucizamab B. Andexenat alfa QD?  Rivaroxaban C. Prothrombin complex 14% concentrate (PCC) 10% 10% D. None of the above Most  Apixaban b a e a f v m a l . . o . b a t o a a z c i n c x e e e u h r x l t e p a d d m f o I n o e A c n n o i N b m o r h t o r P Causes of Death in AF Reversal agents are here! Andexanet alfa Ciraparantab If you bleed, better to be on DOAC than warfarin Idarucizumab Gómez-Outes A and colleagues, JACC 2016 Burnett A, Siegal D, and Crowther M, BMJ 2017 3

6/17/2019 REVERSE-AD (Idarucizamab) ANNEXA-4 (andexanet alfa) % Excellent/Good Hemostatis Diluted thrombin time • Add data re efficacy and safety Uncontrolled bleeding group Urgent procedure group Pollack CV Jr et al, NEJM 2017 Connolly SJ et al, NEJM 2019 When to use reversal agent Mary recovers. 6 months later she presents to your office with chest pain and concerning ECG changes. She ultimately undergoes PCI of 98% LAD lesion. In addition to clopidogrel, you now recommend… Bleeding that is: Procedure that is: • life-threatening • Urgent 54% • into critical organ • Unable to be performed on DOAC A. Apixaban alone • uncontrollable 42% • In pt with relevant DOAC level • related to DOAC B. Apixaban and aspirin C. Switch apixaban to warfarin Reversal agent appropriate D. Switch apixaban to warfarin and 4% 0% X X aspirin X Overdose Trauma Apixaban alone Apixaban and aspirin Switch apixaban to warfarin Switch apixaban to warfar.. Any bleeding/procedure Cuker et al, Am J Hematol 2019 4

6/17/2019 AUGUSTUS – Apixaban alone is best Caveats in AF patients with recent ACS or PCI Major/relevant bleeding Major bleed • 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 Hospitalization Death or ischemic events • Consistent with other AF+PCI DOAC trials • Mean time index event -> randomization = 6.6 days • Likely many received ASA during that time Lopes RD et al, NEJM 2019 New guideline recommendations 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. Class I recommendation to use DOAC over warfarin if You say… I DOAC-eligible for nonvalvular AF 68% Excludes only mod-sev mitral stenosis or mech valve A. Oh yes, it can make you feel better + Class I recommendation for idarucizumab for dabigatran live longer I reversal for life-threatening bleeding or urgent B. Yes, it’s the most effective symptomatic procedure therapy 20% Class IIa recommendation for andexanat alfa for IIa apixaban or rivaroxaban reversal for life-threatening or C. You can, but the AF will come back, it 8% 4% uncontrolled bleeding always does Class IIa recommendations for double instead of triple D. I wouldn’t recommend it at your age . . . . . . . e v . . . . IIa l t f i l i therapy after PCI for ACS if CHA 2 DS 2 -VASc ≥ 2 u t i d c w o e n y f F e f A e e m k t e m a s h m o t o Warfarin, dabigatran, or rivaroxaban m c t n u e a e r b c h t , ’ t t n n i s a d s , ’ c l t i u e u y , o s o w h e Y O Y I January CT et al, Circulation / JACC / Heart Rhythm 2019 5

6/17/2019 CABANA CABANA – Primary Outcome Death, Disabling Stroke, Serious Bleeding, or Cardiac Arrest Total Ablation Meds N = 2204 N = 1108 N = 1096 Age 68 69 Female 37% 37% HTN 79% 82% Diabetes 25% 26% CHA 2 DS 2 -VASc 3 3 (median) Paroxysmal 42% 43% Rhythm control 82% 82% drug Packer DL, et al, JAMA 2019 Packer DL, et al, JAMA 2019 CABANA – Secondary Outcomes CABANA – Per Protocol Analysis Death, Disabling Stroke, Serious Bleeding, or Cardiac Arrest Freedom from AF Mortality or CV Hospitalization Packer DL, et al, JAMA 2019 Packer DL, et al, JAMA 2019 6

6/17/2019 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 7

6/17/2019 Mike is Mary’s 72 year-old husband, whom you manage LVEF Change with AF ablation for heart failure. After his Apple Watch noted irregular heart rhythms, an event monitor confirmed AF. He c/o fatigue. You suggest… 54% A. AF ablation B. Amiodarone 23% C. AVJ ablation and pacemaker 15% 8% D. HF management without directed AF therapy n e r o n e . . i o k . t r a t a l a m u b d o a o e h c F i a t m i A p w A d t Pooled = 13.3% n n a e m n o e i g t a a l n b a a m J V F A H Ganesan et al, Heart, Lung and Circulation 2015 Meta-Analysis of 4 RCTs AATAC-AF: Ablation vs. Amio 70% Arrhythmia free in Ablation Group LVEF QOL Pooled = 8.5% Favors HR Control Favors Ablation Favors Ablation Favors HR Control 34% Arrhythmia free with Amiodarone 6 min walk Peak VO 2 10% discontinuation Favors HR Control Favors Ablation Favors HR Control Favors Ablation Better LVEF, QOL, Di Biase et al, Circulation 2016 Al Halabi et al, JACC: Clin Electrophysiol 2015 HF hosp, + mortality too! 8

6/17/2019 CASTLE-AF: ablation reduces CASTLE-AF HF admissions and mortality Total Ablation Grp Conventional Grp N = 363 N = 179 N = 184 Mean age (yrs) 64 64 Mean LVEF 32.5% 31.5% NYHA Class I/II 69% 72% Risk Reduction: 38% Nonischemic 60% 48% Paroxysmal AF 35% 35% AAD use 32% 30% Marrouche et al, NEJM 2018 Marrouche et al, NEJM 2018 Significant reduction in both AF burden decreased with HF hosp + all-cause mortality ablation All-cause mortality HF Hospitalizations Marrouche et al, NEJM 2018 Marrouche et al, NEJM 2018 9

6/17/2019 Significant interaction by LVEF New guideline recommendation Class IIb recommendation for AF ablation in selected IIb patients with symptomatic AF and heart failure with a reduced EF to potentially lower mortality and reduce HF hospitalizations • 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% January CT et al, Circulation / JACC / Heart Rhythm 2019 Marrouche et al, NEJM 2018 AF: result of occult atrial (and Mike had an ablation and is doing well. Mary is considering it, but asks you if there is anything else ventricular) cardiomyopathy? she could do that might reduce her AF burden and symptoms. You tell her… 48% 38% A. Yes! Weight loss could cure your AF B. Sort of. Exercise can improve symptoms, but doesn’t actually change AF burden. 14% C. No. Just have the ablation already. . . . . u . . . . c p o m i d t l a u i l o n b a a c c s e s e h o s t l i c e t r v h e g a x h i E e W . t f s u o ! J s t e r . o o Y S N Wijesurendra R et al, Circulation 2016 10