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Melissa R. Robinson, MD FACC FHRS CCDSAssistant Professor of Medicine

Director of the Complex Arrhythmia Service

NEW APPROACHES AND NEW ANTICOAGULANTS

FOR ATRIAL FIBRILLATION

MAY 1, 2015

• Scope of the problem• Monitoring for silent AF• Lifestyle Influence (use P’s slides)• OSA• Ablation – cryo, rotors• Combination with LAA closure -- Watchman• NOACs

•Meet the players

•How to chose

•Special considerations• Cases at the end

POINTS TO MAKE

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• Atrial Fibrillation Ablation• Review of Anticoagulants• Agent Selection• Dosing• Percutaneous Left Atrial Appendage

Closure

OUTLINE

PREVALENCE OF AFIB

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AF NOMENCLATURE

2014 AHA/ACC/HRS AF GUIDELINES FOR RHYTHM CONTROL

January C, JACC 2014;64(21):e1

Catheter ablation can be first line therapy in Paroxysmal AF

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• Treatment of comorbidities

•Valve disease

•OSA

•HTN

• Lifestyle changes

•Weight loss

•Exercise

• Patient selection• Technology

IMPROVING OUTCOMES FOR AF ABLATION

Akoum N JCE 2011;22(1):16

ENERGY SOURCES FOR AF ABLATION

Andrade J, Circ Arrhy Electro 2013;6:218

Cryoablation Lesion Radiofrequency Lesion

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CRYOBALLOON ABLATION

• AF increases stroke risk at least 5-fold

• AF accounts for 15-20% of all strokes

• AF associated strokes have higher mortality and morbidity

• AF ultimately found in 20% of cryptogenic strokes

AF AND STROKE

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CRYPTOGENIC STROKE AND AF – CRYSTAL AF

Sanna T et al NEJM 2014; 370:2478

INCIDENCE OF AF IN CIED POPULATION

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HOW MUCH AF IS TOO MUCH?

OAC IN ACUTE CVA PTS WITH KNOWN AF

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CHADS2 CHA2DS2VASC

CHADS2 CHA2DS2VASC

OAC

ASA or OAC

ASA

OAC

ASA or OAC

ASA

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CHA2DS2-VASC SCORE: NEGATIVE PREDICTIVE VALUE

Olsen, JB et al Thrombo and Hemost 2012; 107: 1172-9

DANISH NATIONAL PATIENT REGISTRIES 1997-2008:CHADS2 = 0 OR 1 (N=47,576); NONVALVULAR AF; NO OAC

CALCULATORS

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OAC DECISION TREE IN AF

COAGULATION CASCADE AND OACS

Apixaban, Rivaroxabanand Edoxaban

Dabigitran

Warfarin

January C, JACC 2014;64(21):e1

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WARFARIN V. PLACEBO

64% RRR

NNT : 37 (primary prevention) and 12 (secondary prevention)

Hart et al Ann Intern Med 2007; 146:857-67

n = 2,900; nonvalvular AF

SWEDISH AF COHORT STUDY Swedish National Hospital Discharge Registry 2005-2008:

Study population:n=182,678

nonvalvular AFmean age 76

53% M

Follow-up: 1.5 years Ann

ual e

vent

rat

es

CHA2DS2-VASc score

Friberg et al Circulation 2012; 125: 2298-2307

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NET CLINICAL BENEFIT OF OAC IN AF:ISCHEMIC CVA MINUS HEMORRHAGIC CVA

Friberg et al Circulation 2012; 125: 2298-2307

OAC DECISION TREE IN AF

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ENGAGE AF-TIMI 48

STROKE OR SYSTEMIC EMBOLISM

Ruff, C et al Lancet 2014; 383(9921):955-62

19% reduction in stroke, p = <0.0001

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MAJOR BLEEDING IN THE DOAC TRIALS

Ruff, C et al Lancet 2014; 383(9921):955-62

14% reduction in major bleeding, p = 0.06

EFFICACY AND SAFETY

Ruff, C et al Lancet 2014; 383(9921):955-62

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Renal Function

(mL/min C-G)

Dabigatran(Pradaxa)

Rivaroxaban(Xarelto)

Apixaban(Eliquis)

Edoxaban

CrCl > 50

150mg bid§

20mg qd 5mg bid*

2.5mg bid if any 2 of:

≥ 80 y.o.≤ 60 kgCr ≥ 1.5

60mg qd

CrCl 30-50

15mg qd* 30mg qd

CrCl 15-30 75mg bid§

ESRD or HD Not recommended

If HD, 5mg bid or 2.5mg bid if

>80y.o. or <60kg

Notrecommended

DOSING IN RENAL FAILURE

• Using MDRD may lead to under-dosing of DOACs relative to trial data

CRCL V. GFR (MDRD)

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DOAC: DRUG INTERACTIONSDrug dabigatran rivaroxaban apixaban edoxaban

Verapamil +12-180%, dose minor effect ? +50%, dose

Diltiazem none minor effect +40% ?

Amiodarone +12-60% minor effect ? no effect

P-glycoprotein / CYP3A4 inhibitors

Dronedarone +70-100%, CI ? ? +85%, dose

Ketoconazole +150%, CI +160%, CI +100%, CI ?

Protease inhib ? + 150%, CI ? ?

rifampicin - 66%, CI - 50% -54%, CI -35%

P-glycoprotein / CYP3A4 inducers

St Johns wortcarbemazepinephenytoinphenobarbital

Heidbuchel, H et al Europace 2013; 15:625-51

SPECIFIC SCENARIOS

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• Low risk surgery

•1 day

• Higher risk surgery

•2 days

• these agents for 1 day (2 doses for dabigatran and apixaban;

• 1 dose for rivaroxaban) before the procedure is

• generally sufficient for patients with normal renal function

DISCONTINUATION FOR SURGERY

BLEEDING ON DOAC

Levy et al JACC:CI 2014; 7(12):1333

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• Normal aPTT excludes bleeding from dabigitran

• Prothrombin time usually elevated with apixaban/rivaroxaban/edoxaban

BLEEDING ON DOACS

Levy et al JACC:CI 2014; 7(12):1333

Rivaroxaban Dabigitran ApixabanWarfarin (generic)

Regents $315Preferredstatus

$318 $317 $6.60/mo

Medicaid Preferred Preferred Non-preferred Non-preferred

Premera Tier 2 Tier 2 Tier 2 Non-preferred

Group Health NF NF NF Formulary

Molina Tier 2 Tier 2 Tier 2 Preferred

REIMBURSEMENT CONSIDERATIONS

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Image courtesy of M. Reisman, MD

NONPHARMACOLOGIC STROKE REDUCTION IN AF

LEFT ATRIAL APPENDAGE CLOSURE DEVICES

AmplatzerPLAATO

Watchman LariatBajaj N, JACC:Card Interv 2014;7(3):296

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LEFT ATRIAL APPENDAGE VARIABILITY

• Overall stroke risk 0.7/100 patient years• Procedural failure rate of 7-9%• Access site complication rate 8.6%• Pericardial effusion rate 4.1%

LEFT ATRIAL APPENDAGE CLOSURE

Bajaj N, JACC:Card Interv 2014;7(3):296

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COMPARISION OF STROKE PREVENTION

Bajaj N, JACC:Card Interv 2014;7(3):296

OUT-OF-POCKET COSTS TO MEDICARE PT

Armstrong et al JACC 2014;63(12_S)

• Includes Medicare deductibles and co-insurance for:

•LAAC cost

•Labwork

•Clinic visits

•Acute clinical events

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• AF Catheter ablation techniques continue to improve and outcomes in selected patients are favorable

• Direct oral anticoagulants offer many benefits over warfarin in selected patients

• Left atrial appendage closure is emerging as a new tool for stroke reduction in AF

TAKE HOME POINTS

QUESTIONS?