What’s new in EP?Say no to drugs?

Lionel Faitelson MD FACC FHRSTucson Heart Group

TMC Cardiovascular Symposium 2012

What’s new in EP?Say no to drugs?

Lionel Faitelson MD FACC FHRSTucson Heart Group

TMC Cardiovascular Symposium 2012

New devices for arrhythmias?

Anti-arrhythmic drugs: VT and VFDefibrillators ICDs; ablation

Anti-arrhythmic drugs: SVT and AFL and AFAblation

Anti-heart failure drugsBiventricular pacemakers and ICDs

Anticoagulant drugs in AF: NEWAlternatives to anticoagulant drugs NEW

AF: Managing the LA appendage

• Relevance• Magnitude of AF issue • Risk scores and anticoagulant therapies• Surgical options• Percutaneous options

– Lariat– Watchman– Amplatzer cardiac plug– Other

Atrial Fibrillation Update 2012

Philadelphia 1.5 million

San Francisco 700,000

Miami 400,000 Los Angeles 3.8 million

6.4 million

(H.Weitz MD)

Atrial Fibrillation Update 2035

Philadelphia 1.5 millionSan Francisco 700,000

Boston 600,000

Houston 2 million Los Angeles 3.8 million Chicago 2.8 million

11.4 million

Atrial fibrillation treatment

Atrial fibrillation

March 2010: 1,980,000 hits

March 2011: 2,550,000 hits

January 2012: 9,500,000 hits

AF: Public awareness

• September 2012 is Atrial Fibrillation Awareness Month

• www.MyAfib.org

How do we determine stroke risk ?

• CHADS2 (Gage, et al.: JAMA 2001)– Congestive heart failure - 1pt

– Hypertension - 1pt

– Age > 75 - 1 pt

– Diabetes - 1pt

– Stroke or TIA - 2 pts

– 0 points – low risk (1.2-3.0 strokes per 100 patient years)

– 1-2 points – moderate risk (2.8-4.0 strokes per 100 patient years)

– > 3 points – high risk (5.9-18.2 strokes per 100 patient years)

How do we determine stroke risk ?

• CHADS2 (Gage, et al.: JAMA 2001)– Congestive heart failure - 1pt

– Hypertension - 1pt

– Age > 75 - 1 pt

– Diabetes - 1pt

– Stroke or TIA - 2 pts

– 0 points – low risk (1.2-3.0 strokes per 100 patient years)

– 1-2 points – moderate risk (2.8-4.0 strokes per 100 patient years)

– > 3 points – high risk (5.9-18.2 strokes per 100 patient years)

Lip Y, et al. Chest 2010, 137(2):263

Lip Y, et al. Chest 2010, 137(2):263

CHADS2 vs. CHA2DS2VASc

• CHADS2 score 0: 1.4% events

• CHA2DS2-VASc score 0: 0 events

• CHA2DS2-VASc score 1: 0.6% events

• CHA2DS2-VASc score 2: 1.6 events

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Non-Valvular Atrial Fibrillation Stroke PreventionMedical Rx

Warfarin ProblematicWarfarin Problematic• Narrow therapeutic windowNarrow therapeutic window

• Multiple drug-drug/drug-food interactionsMultiple drug-drug/drug-food interactions• Genetic variabilityGenetic variability

• Long half-life Long half-life • PCI issues – triple therapyPCI issues – triple therapy• ComplianceCompliance• ContraindicationsContraindications• Bleeding risksBleeding risks

Non-Valvular Atrial Fibrillation Warfarin Use in AF Patients by Age

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%%

Ann Int Med 131(12), 1999Ann Int Med 131(12), 1999

• Only 55% of AF patients with no contraindications have evidence of Only 55% of AF patients with no contraindications have evidence of

warfarin use in previous 3 monthswarfarin use in previous 3 months• Other studies cite warfarin use in AF patients from 17-50%Other studies cite warfarin use in AF patients from 17-50%• Elderly patients with increased absolute risk least likely to be taking Elderly patients with increased absolute risk least likely to be taking

warfarinwarfarin• Contraindications 30-40%Contraindications 30-40%

Atrial fibrillation 2009Target INR 2-3

Non-Valvular Atrial Fibrillation Adequacy of Anticoagulation in Clinic

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%%

Bungard: Pharmacotherapy 20:1060, 2001Bungard: Pharmacotherapy 20:1060, 2001

Low INR <1.6Low INR <1.6

TherapeuticTherapeuticINR 2-3INR 2-3

High INR >3.2High INR >3.2

Efficacy Efficacy 4-fold 4-fold

Non-Valvular Atrial FibrillationStroke Pathology

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Brass. Stroke 28(12), 1997Brass. Stroke 28(12), 1997VanWalraven: JAMA 288, 2002VanWalraven: JAMA 288, 2002

• Major fatal bleed with age >75 = 3%/year (30% over Major fatal bleed with age >75 = 3%/year (30% over 10 years)10 years)

• Intracranial hemorrhageIntracranial hemorrhage• 0.3-0.5%/100 patient-years0.3-0.5%/100 patient-years• 3% in INR >4.03% in INR >4.0• 10% if INR >4.510% if INR >4.5

Non-Valvular Atrial FibrillationStroke Pathology

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Blackshear: Ann Thoracic Surg 61, 1996Blackshear: Ann Thoracic Surg 61, 1996Johnson: Eur J Cardiothoracic Surg 17, 2000Johnson: Eur J Cardiothoracic Surg 17, 2000Fagan: Echocardiography 17, 2000Fagan: Echocardiography 17, 2000

• Insufficient contraction of LAA leads to stagnant Insufficient contraction of LAA leads to stagnant blood flowblood flow

• Most likely culprit: embolization of LAA clotMost likely culprit: embolization of LAA clot

• 90% of thrombus found in LAA90% of thrombus found in LAA

• TEE-based risk factorsTEE-based risk factors•Enlarged LAAEnlarged LAA•Reduced inflow and outflow velocitiesReduced inflow and outflow velocities•Spontaneous Echo contrastSpontaneous Echo contrast

Warfarin

• Effective• Reversible• Inexpensive

• Slow onset of action• Regular monitoring• Food interraction• Medication interraction• Difficult titration-regular dose adjustments

Warfarin

• Effective• Reversible• Inexpensive

• Slow onset of action• Regular monitoring• Food interraction• Medication interraction• Difficult titration-regular dose adjustments

RELY

• Dabigatran 110 mg twice daily– Equal to warfarin in stroke prevention

• Warfarin 1.69%/yr – dabigatran (110mg) 1.53%/yr

– Less bleeding than warfarin• Warfarin 3.36%/year – dabigatran (110mg) 2.71%/yr

• Dabigatran 150 mg twice daily– More effective than warfarin in stroke prevention

• Dabigatran (150mg) 1.11%/yr

– Equivalent bleeding to warfarin

less hemorrhagic stroke than warfarin

ACC AHA HRS Afib Focused Update(Dabigatran), March 2011

• Non-inferior to warfarin re thromboembolism (afib)• Caution when CrCl < 30ml/min• Increased dabigatran levels with amiodarone, verapamil• Half life 12-17 hours• No reversal re hemorrhage

– dialysis

• ? shelf life once bottle opened (FDA alert March 30, 2011)– Tablets must stay in manufacturer’s container

– Label: discard product 30 days after opening container

• Coagulation testing ??? aPTT, dilute thrombin time

Dabigatran compared to control (warfarin, enoxaparin, placebo)

Increased absolute risk of MI or ACS 0.27%

Increased relative risk of MI or ACS 33%

Dabigatran compared to control (warfarin, enoxaparin, placebo)

Increased absolute risk of MI or ACS 0.27%

Increased relative risk of MI or ACS 33%

Rivaroxaban

• Once daily• As effective or better than warfarin• Less hemorrhagic stroke than warfarin• Similar reduction in ischemic stroke• Less bleeding than warfarin• No routine lab testing• No reversal

– Half life 5-9 hours• Coagulation testing: aPTT

• Discontinuation : increased stroke

Apixaban

• Twice daily• As effective or better than warfarin• Less hemorrhagic stroke than warfarin• Similar reduction in ischemic stroke• Less bleeding than warfarin• Lower overall mortality• No routine lab testing• No reversal

– Half life 8-15 hours• Coagulation testing: PT, aPTT

New anticoagulants

• Short half life – less bleeding– Subtherapeutic if misses one or two doses

• Lack of need for routine monitoring– No standard available test to asses if anticoagulated

• Generally safer than warfarin– No antidote

– ??? Dabigatran

• Cost of medication– Overall cost of care

How about Clopidogrel + Aspirin ?

N Engl J Med online publication March 31, 2009

How about Clopidogrel + Aspirin ?

N Engl J Med online publication March 31, 2009

Aspirin: stroke 3.4% per year

major bleed 1.27% per year

Aspirin + clopidogrel:stroke 2.4% per yearmajor bleed 2.0% per year

Warfarin still first line? Role of aspirin + clopidogrel

Aspirin: stroke 3.4% per year

major bleed 1.27% per year

Aspirin + clopidogrel:stroke 2.4% per yearmajor bleed 2.0% per year

Warfarin still first line? Role of aspirin + clopidogrel

LAA: Focus of interest in AF

• Anticoagulants contra-indicated in 14 – 44% AF patients

• Stroke risk 2-5% even with therapeutic INR• LAA – 90% of thrombi in nonvalvular

nonrheumatic AF• LAA volume 0.77 – 19.27 cc• LAA variable anatomy – multimodality imaging• Luis, Roper et al; Cardiology Research and Practice 2012

LAA: Surgical options

• Excision with oversew or staples• Exclusion with clips or sutures• LAA Occlusion Study: success 45-72%• LAA Surgery: excision 73% > exclusion 23%• LAA Atriclip: EXCLUDE trial: 98% success• Current surgical practice

201120001985195519491947

Ligation of the Left Atrial Appendage Using an

Automatic StaplerVJ DiSesa, S Tam, LH CohnDivision of Cardiac Surgery, Brigham & Women’s Hospital, Boston, MA

Appendage Obliteration to Reduce Stroke in Cardiac Surgical Patients with Atrial FibrillationJL Blackshear, MD, JA Odell, FGRCS(Ed)Division of Cardiovascular Diseases, Mayo Clinic Jacksonville FL & Mayo Clinic, Rochester, MN

Resection of the Left Auricular AppendixA Prophylaxis for Recurrent

Arterial EmboliJOHN L. MADDEN, M.D.

Department of Surgery, Long Island College of Medicine, Kings County Hospital, Brooklyn , NY

Amputation of the Canine Atrial AppendagesHellerstein, HK

USE OF THE SURGICAL STAPLER TO OBLITERATE

THE LEFT ATRIAL APPENDAGE

Laurence H. Coffin, M.D., F.A.C.S., Burlington, VT

SYSTEMIC EMBOLISM AND LEFT AURICULAR

THROMBOSIS IN RELATION TO MITRAL

VALVOTOMY BYAND

J. R. BELCHER, M.S., F.R.C.S. Surgeon, London Chest Hospital; Assistant Thoracic Surgeon, the Middlesex Hospital

History of Suture Closure

LAA: Lariat

• Prospective study; 82 pts; 3 month FU• Indications: AF; warfarin intolerance or CI, or embolic event

on warfarin• 96% of pts with successful closure have closure at 1 month• Need epicardial and endocardial access (CABG, XRT, valve

surgery, pericarditis)• Unsuitable if pericardial adhesions present• FDA and CE approved

• Lee at al; Heart Rhythm 2011

Pre-Clinical ResultsObjective

Evaluate safety & effectiveness in canine model of percutaneous LAA closure with the LARIAT

N=26 canines

Complete Acute Closure: 26/26 (100%)

Histological Examination (all)

1 attempt: 23/26 ( 88%)

Attempts to Capture

2 attempt: 3/26 ( 12%)

7d Closure: 3/3 (100%)

30d Closure: 3/3 (100%)

90d Closure: 4/4 (100%)

Inflammatory response: 0/10 ( 0%)

Complete Endothelioization: 10/10 (100%)

Circ Cardiovasc Interv: June 2010

Clinical Results – PLACE ITotal Total PatientsPatients

N=13

AF HistoryAF History Persistent 12 (92%)Flutter 1 ( 8%)

AgeAge Avg: 57.3; Hi 64, Low 43

SexSex M = 8 (62%)

Type Type ProcedureProcedure

LAA w/ MVR 2 (15%)LAA w/ ablation 10 (77%)Ablation w/ LAA 1 ( 8%)

Type Type AccessAccess

Median Sternotomy 2 (15%)Minimally Invasive 2 (15%)Percutaneous 9 (70%)

Intent to Intent to TreatTreat

12/13 (92%)

Acute Acute Closure Closure

12/12 (100%)

ComplicatComplicationsions

1/13 (8%) non-serious (anatomic)

ProceduraProcedural Timesl Times

Avg: 85.7 min; Median 55 +84.9min

Heart Rhythm: 2011:8:188 - 193

Closure Without Compromise

LAA Pre-procedure 30 day Post-procedure

PLACETM

ProcedurePermanent Ligation Approximation Closure and Exclusion

PLACETM

Procedure

Clinical Results – Confidence in Closure

In a single center, non randomized study(PLACE II)*, 85 patients underwent closure of their left atrial appendage using the LARIAT Suture Delivery Device and accessories. Patients were followed at 1 day, 30 days, 90 days and 1 year with transesophageal echocardiography to determine closure quality. The results were as follows:

* PLACE II Clinical Study -KBET/90/B/2008; Dec 2009 - Jun 2011. Submitted for publication.** All non-serious: 2 pericardial access related. 1 transseptal access related.

Intent-to-Treat 85/89 (96%)

Adverse Events(defined as access related or device

failure)

3/89 (3.3%)**Access 3/89 (3.3%)Device 0/89 (0.0%)

Closure (defined as < 1mm residual

flow)

1 day 81/85 (95%)30 day 81/85 (95%)90 day 77/81 (95%)1 year 65/66 (98%)

LAA: Watchman

WATCHMAN® LAA Closure Technology

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LAA: Watchman

• PROTECT AF (RCT); 707 pts; 18 month FU• Indication: Permanent or Paroxysmal AF; CHADS >1; suitable

for warfarin• Noninferiority of the intervention demonstrated• CE approved

• Reddy et al; Circulation 2011

PROTECT AF Clinical Trial Design

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• Prospective, randomized study of WATCHMAN LAA Device vs long-term Prospective, randomized study of WATCHMAN LAA Device vs long-term warfarin therapywarfarin therapy

• 2:1 allocation ratio device to control2:1 allocation ratio device to control

• 800 patients enrolled from Feb 2005 to Jun 2008800 patients enrolled from Feb 2005 to Jun 2008• Device group (463)Device group (463)• Control group (244)Control group (244)• Roll-in group (93)Roll-in group (93)

• 59 enrolling centers (U.S. & Europe)59 enrolling centers (U.S. & Europe)

• Follow-up requirementsFollow-up requirements• TEE follow-up at 45 days, 6 months and 1 yearTEE follow-up at 45 days, 6 months and 1 year• Clinical follow-up biannually up to 5 yearsClinical follow-up biannually up to 5 years• Regular INR monitoring while taking warfarinRegular INR monitoring while taking warfarin

• Enrollment continues in Continued Access Protocol (CAP Study)Enrollment continues in Continued Access Protocol (CAP Study)

Key Participation Criteria

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Key inclusion criteriaKey inclusion criteria• Age 18 years or olderAge 18 years or older• Documented non-valvular AFDocumented non-valvular AF• Eligible for long-term warfarin therapy, and has no other conditions that Eligible for long-term warfarin therapy, and has no other conditions that

would require long-term warfarin therapywould require long-term warfarin therapy• Calculated CHADS2 score Calculated CHADS2 score 11

Key exclusion criteriaKey exclusion criteria• NYHA class IV congestive heart failureNYHA class IV congestive heart failure• ASD and/or atrial septal repair or closure deviceASD and/or atrial septal repair or closure device• Planned ablation procedure within 30 days of potential Planned ablation procedure within 30 days of potential

WATCHMAN Device implantWATCHMAN Device implant• Symptomatic carotid diseaseSymptomatic carotid disease• LVEF <30% LVEF <30% • TEE criteria: suspected or known intracardiac thrombus (dense TEE criteria: suspected or known intracardiac thrombus (dense

spontaneous Echo contractspontaneous Echo contract

PROTECT AF Trial Endpoints

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• Primary efficacy endpointPrimary efficacy endpoint

• All stroke: ischemic or hemorrhagic All stroke: ischemic or hemorrhagic • Deficit with symptoms persisting more than 24 hours or Deficit with symptoms persisting more than 24 hours or • Symptoms less than 24 hours confirmed by CT or MRISymptoms less than 24 hours confirmed by CT or MRI

• Cardiovascular and unexplained death: includes sudden death, MI, Cardiovascular and unexplained death: includes sudden death, MI, CVA, cardiac arrhythmia and heart failure CVA, cardiac arrhythmia and heart failure

• Systemic embolizationSystemic embolization

• Primary safety endpoint Primary safety endpoint

• Device embolization requiring retrievalDevice embolization requiring retrieval• Pericardial effusion requiring interventionPericardial effusion requiring intervention• Cranial bleeds and gastrointestinal bleedsCranial bleeds and gastrointestinal bleeds• Any bleed that requires Any bleed that requires 2uPRBC2uPRBC

Some events will be counted as both Some events will be counted as both safety and efficacy endpointssafety and efficacy endpoints

Intent-to-TreatIntent-to-TreatPrimary Safety ResultsPrimary Safety Results

ITT cohort: patients ITT cohort: patients analyzed based on their analyzed based on their randomly assigned group randomly assigned group (regardless of treatment (regardless of treatment received)received)Ev

ent-

free

pro

babi

lity

Even

t-fr

ee p

roba

bilit

y

DaysDays244244 143143 5151 1111463463 261261 8787 1919

DeviceDevice

ControlControl

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EventsEvents TotalTotal RateRate EventsEvents TotalTotal RateRate RRRRCohortCohort (no.)(no.) pt-yrpt-yr (95% CI)(95% CI) (no.)(no.) pt-yrpt-yr (95% CI)(95% CI) (95% CI)(95% CI)

600 pt-yr600 pt-yr 4545 386.4386.4 11.611.6 99 220.4220.4 4.14.1 2.852.85(8.5, 15.3)(8.5, 15.3) (1.9, 7.2)(1.9, 7.2) (1.48, 6.43)(1.48, 6.43)

900 pt-yr900 pt-yr 4848 554.2554.2 8.78.7 1313 312.0312.0 4.24.2 2.082.08(6.4, 11.3)(6.4, 11.3) (2.2, 6.7)(2.2, 6.7) (1.18, 4.13)(1.18, 4.13)

DeviceDevice ControlControl

900 patient-year analysis900 patient-year analysis

Randomization Randomization allocation (2 device:1 allocation (2 device:1 control)control)

Specific Safety Endpoint Events

• Pericardial effusions – largest fraction of Pericardial effusions – largest fraction of safety events in device groupsafety events in device group

• Stroke events – most serious fraction of Stroke events – most serious fraction of safety events in control groupsafety events in control group

• Bleeding events were also frequent Bleeding events were also frequent

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Pericardial Effusions by Experience

• Throughout PROTECT AF Trial, procedural modifications and training Throughout PROTECT AF Trial, procedural modifications and training enhancements were implemented enhancements were implemented

• Procedural events would be expected to decrease over timeProcedural events would be expected to decrease over time• Pericardial effusions within 7 days of the procedure are most Pericardial effusions within 7 days of the procedure are most

relevant to the device performancerelevant to the device performance

No.No. %% No.No. %% No.No. %%

Early patients (1-3)Early patients (1-3) 13/15413/154 8.48.4 12/15412/154 7.87.8 10/15410/154 6.56.5

Late patients (Late patients (4)4) 27/38827/388 7.07.0 24/38824/388 6.26.2 17/38817/388 4.44.4

TotalTotal 40/54240/542 7.27.2 36/54236/542 6.66.6 27/54227/542 5.05.0

Site implant group Site implant group (includes roll-in (includes roll-in

subjects)subjects) AnyAny

Any procedure/ Any procedure/ device relateddevice related Any Any

seriousserious

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Effusions in Recent Implant Experience

• Rates obtained in the CONTINUED ACCESS Study confirm Rates obtained in the CONTINUED ACCESS Study confirm that the lower rates are sustainedthat the lower rates are sustained

No.No. %% No.No. %% No.No. %%

1/881/88 1.11.1 1/881/88 1.11.1 1/881/88 1.11.1

AnyAny

Any procedure/ Any procedure/ device relateddevice related Any Any

seriousserious

Intent-to-TreatIntent-to-TreatPrimary Efficacy ResultsPrimary Efficacy Results

ITT cohort: patients ITT cohort: patients analyzed based on their analyzed based on their randomly assigned group randomly assigned group (regardless of treatment (regardless of treatment received)received)Ev

ent-

free

pro

babi

lity

Even

t-fr

ee p

roba

bilit

y

DaysDays244244 147147 5252 1212463463 270270 9292 2222

WATCHMANWATCHMAN

ControlControl

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900 patient-year analysis900 patient-year analysis

EventsEvents TotalTotal RateRate EventsEvents TotalTotal RateRate RRRR Non-Non- SuperioritySuperiorityCohortCohort (no.)(no.) pt-yrpt-yr (95% CI)(95% CI) (no.)(no.) pt-yrpt-yr (95% CI)(95% CI) (95% CI)(95% CI) inferiorityinferiority

600600 1818 409.3409.3 4.44.4 1313 223.6223.6 5.85.8 0.760.76 0.9920.992 0.7340.734pt-yrpt-yr (2.6, 6.7)(2.6, 6.7) (3.0, 9.1)(3.0, 9.1) (0.39, 1.67)(0.39, 1.67)

900900 2020 582.3582.3 3.43.4 1616 318.0318.0 5.05.0 0.680.68 0.9980.998 0.8370.837pt-yrpt-yr (2.1, 5.2)(2.1, 5.2) (2.8, 7.6)(2.8, 7.6) (0.37, 1.41)(0.37, 1.41)

DeviceDevice ControlControl Posterior probabilitiesPosterior probabilities

Randomization Randomization allocation (2 device:1 allocation (2 device:1 control)control)

Intent-to-TreatIntent-to-TreatHemorrhagic StrokeHemorrhagic Stroke

ITT cohort: patients analyzed ITT cohort: patients analyzed based on their randomly based on their randomly assigned group (regardless of assigned group (regardless of treatment received)treatment received)

Even

t-fr

ee p

roba

bilit

yEv

ent-

free

pro

babi

lity

DaysDays244244 147147 5353 1212463463 275275 9595 2323

DeviceDevice

ControlControl

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900 patient-year analysis900 patient-year analysis

EventsEvents TotalTotal RateRate EventsEvents TotalTotal RateRate RRRR Non-Non- SuperioritySuperiorityCohortCohort (no.)(no.) pt-yrpt-yr (95% CI)(95% CI) (no.)(no.) pt-yrpt-yr (95% CI)(95% CI) (95% CI)(95% CI) inferiorityinferiority

600600 11 416.7416.7 0.20.2 44 224.7224.7 1.81.8 0.130.13 0.9980.998 0.9860.986pt-yrpt-yr (0.0, 0.9)(0.0, 0.9) (0.5, 3.9)(0.5, 3.9) (0.00, 0.80)(0.00, 0.80)

900900 11 593.6593.6 0.20.2 66 319.4319.4 1.91.9 0.090.09 >0.999>0.999 0.9980.998pt-yrpt-yr (0.0, 0.6)(0.0, 0.6) (0.7, 3.7)(0.7, 3.7) (0.00, 0.45)(0.00, 0.45)

DeviceDevice ControlControl Posterior probabilitiesPosterior probabilities

Randomization Randomization allocation (2 device:1 allocation (2 device:1 control)control)

Risk/Benefit AnalysisRisk/Benefit Analysis• Intent-to-treat analysisIntent-to-treat analysis

• Primary endpoint (intent to treat) achievedPrimary endpoint (intent to treat) achieved

• Other statistically significant endpoint findingsOther statistically significant endpoint findings• Noninferiority for the primary efficacy event rate – 32% lower in device Noninferiority for the primary efficacy event rate – 32% lower in device

groupgroup• Noninferiority for stroke rate – 26% lower in device groupNoninferiority for stroke rate – 26% lower in device group• Superiority for hemorrhagic stroke – 91% lower in device groupSuperiority for hemorrhagic stroke – 91% lower in device group• Noninferiority for mortality rate – 39% lower rate in device groupNoninferiority for mortality rate – 39% lower rate in device group

• Increased rate of primary safety events for the device group relative to the Increased rate of primary safety events for the device group relative to the control group control group

• Most events in the device group were procedural effusions that Most events in the device group were procedural effusions that decreased over the course of the studydecreased over the course of the study

• 87% of patients discontinued warfarin at 45 days87% of patients discontinued warfarin at 45 days• Death/disability conclusionDeath/disability conclusion

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Risk / Benefit AnalysisRisk / Benefit Analysis

Per-protocol analysisPer-protocol analysis

• Superiority for the primary efficacy event rateSuperiority for the primary efficacy event rate

• Approximately 86% of patients in the device group Approximately 86% of patients in the device group were able to be successfully implanted and were able to be successfully implanted and discontinue warfarin therapydiscontinue warfarin therapy

• Study demonstrates the role of the left atrial Study demonstrates the role of the left atrial appendage in the pathogenesis of stroke due to AFappendage in the pathogenesis of stroke due to AF

• Based on average age, patients will experience a 56% Based on average age, patients will experience a 56% reduction in safety eventsreduction in safety events

Risk/Benefit AnalysisRisk/Benefit Analysis

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Summary

• Long-term warfarin treatment of patients with AF has been found Long-term warfarin treatment of patients with AF has been found effective, but presents difficulties and riskeffective, but presents difficulties and risk

• PROTECT AF trial was a randomized, controlled, statistically valid PROTECT AF trial was a randomized, controlled, statistically valid study to evaluate the WATCHMAN device compared to warfarinstudy to evaluate the WATCHMAN device compared to warfarin

• In PROTECT AF, hemorrhagic stroke risk is significantly lower with the In PROTECT AF, hemorrhagic stroke risk is significantly lower with the device.device.

• When hemorrhage occurred, risk of death was markedly When hemorrhage occurred, risk of death was markedly increasedincreased

• In PROTECT AF, all cause stroke and all cause mortality risk are In PROTECT AF, all cause stroke and all cause mortality risk are equivalent to that with warfarinequivalent to that with warfarin

• In PROTECT AF, there are early safety events, specifically pericardial In PROTECT AF, there are early safety events, specifically pericardial effusion; these events have decreased over timeeffusion; these events have decreased over time

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ConclusionThe WATCHMAN LAA Technology offers a safe and effective alternative to warfarin in patients with non-valvular atrial fibrillation at risk for stroke and who are eligible for warfarin therapy

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LAA: Amplatzer Cardiac Plug

• Different from Amplatzer Septal Occluder• Registry; 141 pts; 24 hour FU• Indication: Permanent/paroxysmal AF• Early experience: Stroke 2.1%, device embolization 1.4%,

tamponade 3.5%• Clinical trial pending• CE 12/2008

• Park et al; CCI 2011

LAA: Other devices• Coherex Wave Crest

– self expanding nitinol with coils and anchors and PTFE covering toward LA; LAA plug

– actively recruiting• PLAATO

– self expanding nitinol cage with anchors and PTFE covering

– 2 prospective trials: 111 and 64 pts– FU 10 months to 5 years– TIA/CVA 2.2% - CVA 3.8%– no longer available for clinical use

Left Atrial Appendage Closure

• Multiple indications• Multiple approaches• CE and FDA issues• Closure