transcatheter laa closure: why, when & in whomadherence to oac proportion of days covered 54.1...

Transcatheter LAA Closure: Why, When & InWhom

SCRIPPS CLINIC

Matthew J. Price MDDirector, Cardiac Catheterization Laboratory, Scripps ClinicLa Jolla, CA, USAEmail: [email protected]: 858-824-5269

The left atrial appendage: our most lethal human attachment!Surgical implicationsq

W. Dudley Johnsona,* , A.K. Ganjoob, Christopher D. Stonec, Ramahalli C. Srivyasa,Mary Howarda,d

European Journal of Cardio-thoracic Surgery 17 (2000) 718±722

www.elsevier.com/locate/ejcts

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• The LAA is the source of thrombus in most AFpatients with thromboembolic events

Adherence to OACProportion of Days Covered

54.148.7 50.1 50.1

4240

50

60

CHA2DS2VASc score ≥4

here

nc

e

Median: 1.1 yrs

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©2018 MFMER | slide-23

0

10

20

30

Apixaban Dabigatran Rivaroxaban All NOACs Warfarin

%A

dh

e

Yao et al: J Am Heart Assoc doi:10.1161/JAHA.115.003074, 2016

THE NOACS: CLINICAL TRIAL SUMMARY

RERE--LYLY ROCKETROCKET--AFAF ARISTOTLEARISTOTLE ENGAGEENGAGE--AFAF

DrugDrug DabigatranDabigatran150mg/d150mg/d

RivoraxabanRivoraxaban20mg/day20mg/day

ApixabanApixaban5mg bid5mg bid

EdoxabanEdoxaban60mg/day60mg/day

CHADSCHADS22 2.22.2 3.53.5 2.12.1 2.82.8

TTR, controlTTR, control 67%67% 58%58% 66%66% 68%68%

IschemicIschemic 0.760.76 (0.60(0.60-- 0.940.94 (0.75(0.75-- 0.920.92 (0.74(0.74-- 1.001.00 (0.83(0.83--

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strokestroke 0.98)0.98) 1.17)1.17) 1.14)1.14) 1.19)1.19)

HemorrhagicHemorrhagicstrokestroke

0.260.26 (0.14(0.14--0.49)0.49)

0.590.59 (0.37(0.37--0.93)0.93)

0.510.51 (0.34(0.34--0.75)0.75)

0.540.54 (0.38(0.38--0.77)0.77)

AllAll--causecausemortalitymortality

0.880.88 (0.77(0.77--1.00)1.00)

0.850.85 (0.70(0.70--1.02)1.02)

0.890.89 (0.80(0.80--0.998)0.998)

0.920.92 (0.83(0.83--1.01)1.01)

Major bleedMajor bleed 0.930.93 (0.81(0.81--1.07)1.07)

1.041.04 (0.90(0.90--1.20)1.20)

0.690.69 (0.60(0.60--0.80)0.80)

0.800.80 (0.71(0.71--0.91)0.91)

GI bleedingGI bleeding 1.501.50 (1.19(1.19--1.89)1.89)

1.391.39 (1.19(1.19--1.61)1.61)

0.890.89 (0.70(0.70--1.15)1.15)

1.231.23 (1.02(1.02--1.50)1.50)

WATCHMAN LEFT ATRIAL APPENDAGE OCCLUDER

CatheterCatheter--based Deliverybased Delivery Available sizes: 21, 24, 27, 30, 33 mmAvailable sizes: 21, 24, 27, 30, 33 mm

diameterdiameter

IntraIntra--LAA designLAA design•• Avoids contact with left atrial wall toAvoids contact with left atrial wall to

help prevent complicationshelp prevent complications

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help prevent complicationshelp prevent complications

NitinolNitinol FrameFrame•• 10 active fixation anchors10 active fixation anchors -- designeddesigned

to engage tissue for stabilityto engage tissue for stability

Proximal FaceProximal Face•• 160 micron membrane PET cap160 micron membrane PET cap

designed to block emboli and promotedesigned to block emboli and promotehealinghealing

WATCHMAN: Clinical Trial Timeline (Manufacturer sponsor/support)

2002 PilotN=66Non-randomizedFeasibility andSafety

2008 CAPRegistryN=566Non-randomizedAdd’l patientsand follow-up

2010 PREVAILN=407RandomizedComparison:warfarin

2012 CAP2RegistryN=579Non-RandomizedAdd’l patientsand follow-up

2017 ASAP TOON= Up to 888RandomizedUS IndicationExpansionWorldwide study

Mar 2015Mar 2015FDA ApprovalFDA Approval

2019 OPTIONN=TBDRandomizedComparison: OAC*trial design indevelopment2017

WATCH-TAVRN=312RandomizedTAVR+WATCHMAN

2005 PROTECT AFN=707RandomizedComparison: warfarin

2009 ASAPN=150Non-randomizedPatients Contra-indicated to warfarin*

2013 EWOLUTION, WASPRegistriesN=1020, N=201Non-randomizedReal-world, All comers

2016 US NESTed NCDR LAAORegistryN=2000Post-approval statistical analysis

2017 SALUTEN= 42Non-randomizedJapanese ApprovalStudy 2018 PINNACLE

FLXN=400Non-randomizedFLX DeviceUS IDE

2002 2013 2018

*Not US Indication

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TWO PROSPECTIVE RANDOMIZED, NON-INFERIORITY TRIALS OF LAA CLOSURE VS. WARFARIN

POST-PROCEDURAL ADJUNCTIVE PHARMACOTHERAPY IN THE WATCHMAN CLINICALTRIALS

SCRIPPS CLINICPrice MJ et al, JACCPrice MJ et al, JACC CardiovascCardiovasc IntervInterv 2015; 8:19252015; 8:1925--32.32.

HR p-value

Efficacy 0.82 0.3

All stroke or SE 0.96 0.9

Ischemic stroke or SE 1.7 0.08

PATIENT-LEVEL PROTECT AF/PREVAIL META-ANALYSIS AT 5 YEARS: WATCHMAN LAACCOMPARED WITH WARFARIN

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Hemorrhagic stroke 0.2 0.0022

Ischemic stroke or SE >7 days 1.4 0.3

CV/unexplained death 0.59 0.03

All-cause death 0.73 0.04

Major bleed, all 0.91 0.6

Major bleeding, non procedure-related 0.48 0.0003

0.01 0.1 1 10

Favors WATCHMAN Favors warfarin

Hazard Ratio (95% CI)JACC 2017

1.50%

2.00% Disabling/Fatal Strokes Non-Disabling Strokes

PATIENT-LEVEL META-ANALYSIS: WATCHMAN ASSOCIATED WITH SUPERIOR REDUCTIONIN DISABLING STROKES

55%

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0.00%

0.50%

1.00%

WATCHMAN warfarin

Disabling Stroke defined as MRS ≥2

HR 0.45 (0.21 – 0.94)P=0.03

55%Reduction

Reddy VY et al. J Am Coll Cardiol. 2017;70(24):2964-75

90

100

WATCHMAN

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Free ofMajor

BleedingEvent

(%)

6 6046 1808 4550

60

70

80

0 7

Warfarin+Aspirin

Warfarin+Aspirin

Plavix+Aspirin Aspirin

WATCHMANWarfarin

72%Relative ReductionIn Major Bleeding

WATCHMANArm

HR 0.28 [95% CI, 0.23 to 0.35]

Price MJ et al, JACCPrice MJ et al, JACC CardiovascCardiovasc IntervInterv 2015; 8:19252015; 8:1925--32.32.

TYPES AND FREQUENCIES OF LATE BLEEDS IN THE WATCHMAN RCTS

SCRIPPS CLINICPrice MJ et al, JACCPrice MJ et al, JACC CardiovascCardiovasc IntervInterv 2015; 8:19252015; 8:1925--32.32.

OUTCOMES IN THE INITIAL WATCHMAN POST-APPROVAL COMMERCIAL EXPERIENCE(N=3822)

Post-FDA Approval Post-FDA Approval

ExperienceExperience

ComplicationsComplications

Pericardial TamponadePericardial Tamponade 39 (1.02%)39 (1.02%)

Treated with Pericardiocentesis Treated with Pericardiocentesis 24 (0.63%)24 (0.63%)

Treated Surgically Treated Surgically 12 (0.31%)12 (0.31%)

Resulted in Death Resulted in Death 3 (0.078%)3 (0.078%)

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Resulted in Death Resulted in Death 3 (0.078%)3 (0.078%)

Pericardial Effusion – No InterventionPericardial Effusion – No Intervention 11 (0.29%)11 (0.29%)

Procedure-Related StrokeProcedure-Related Stroke 3 (0.078%)3 (0.078%)

Device EmbolizationDevice Embolization 9 (0.24%)9 (0.24%)

Removed Percutaneously Removed Percutaneously 33

Removed Surgically Removed Surgically 66

DeathDeath

Procedure-Related Mortality Procedure-Related Mortality 3 (0.078%)3 (0.078%)

Additional Mortality within 7 days Additional Mortality within 7 days 1 (0.026%)1 (0.026%)

Holmes DR, JACC 2017Holmes DR, JACC 2017

LAAC COMPLICATION RATES IN PERSPECTIVE: TAMPONADE RATES IN PROGRESS CTOREGISTRY

In-hospital MACE: components

MI 1%

Tamponade requiringpericardiocentesis 0.9%

N = 3,055

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pericardiocentesis 0.9%

Death 0.8%

Re-PCI 0.3%

Emergent CABG 0.2%

Stroke 0.2%

MACE 3%

WATCHMAN FLX: Design Features18 Strut Frame

Full or Partial RecaptureMinimum LAA Depth = ½ Device Size

10 Strut FramePartial Recapture

Minimum LAA Depth = Ostium Dia.

WATCHMAN WATCHMAN FLX

Closed Distal EndControlled Deployment

Two Rows of18 Anchors

‘J’ anchor'Straight’ anchor

One row of10 Anchors

Price MJ, ACC 2019

ASAP-TOO RANDOMIZED CLINICAL TRIAL

Study ObjectiveEvaluate LAA Closure with WATCHMAN in NVAF patients deemed not suitable for OAC

Study DesignProspective, multi-centerRandomized 2:1 (Watchman vs Control)

Primary Endpoint

Effectiveness EndpointTime to first occurrence of ischemic stroke or systemic embolism

Safety Endpoint7-day rate of all-cause death, ischemic stroke, systemic embolism, or device- or

Primary Endpoint7-day rate of all-cause death, ischemic stroke, systemic embolism, or device- orprocedure- related events requiring open cardiac surgery or major endovascularintervention

Patient Population 888

Number of Sites 100 global sites

Follow-up*

• 3 month with TEE• 6,18 month phone visit• 12 month with TEE• Bi-annually for years 2-5

Holmes et al. AHJ 2017;189: 68-74.

ASAP-TOO RANDOMIZATION ASSIGNMENTS

Visit Interval Aspirin Clopidogrel*

Discharge through3-month visit

Yes, suggested dose:75-100mg

YesSuggested dose: 75mg

3-month visit through12-month visit**

Yes, suggested dose:75-100mg

No, unless otherindication

Device Group Medical Therapy Control Group Treatment

• Single antiplatelet therapy or notherapy for the duration of the trialat the discretion of the studyphysician.

12-month visit** 75-100mg indication

Following the12-month visit**



*Clopidogrel may be substituted with ticagrelor or prasugrel if the subject requires the medication forother indications (e.g. acute coronary syndromes treated with drug eluting stents) or if the subjecthas a known resistance to clopidogrel.

**Patients are allowed to be on dual antiplatelet therapy (outside of the protocol required 3- monthsperiod) if indicated due to a condition other than WATCHMAN implantation.

Holmes et al. AHJ 2017; 189:68-74

• Subjects will be allowed to be ondual antiplatelet therapy ifindicated.

MY DECISION MAKING SCHEME FOR STROKE PREVENTION THERAPY IN AF

2 2

AF patient at highthromboembolic risk byCHA2DS2VASC score

Low bleeding risk,Low bleeding risk,Not good candidate for long-term OAC (prior bleed, Absolute or strong

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preferences

Low bleeding risk,compliant, can afford

therapy, no strong patientpreferences

NOAC

Not good candidate for long-term OAC (prior bleed,bleeding risk, on APT, non-compliant, treatmentfailure, poor VKA candidate & can’t afford/take

NOAC) but can tolerate short-term therapy

Commercial WatchmanLAA Closure

Absolute or strongcontraindication to even

short-term OAC

ASAP-TOO

(WM vs notherapy)

QUARTERLY LAAO PROCEDURES IN THE UNITED STATES*

33403903

4231

5037 50805562

6111

4000

6000

8000

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18 31 92 223737

13541658

2197 24272949

3340

0

2000

4000

*Entered into NCDR LAAO Registry

Price MJ for the NCDR LAAO steering committee, September 2019 San Francisco, CA

CUMULATIVE NUMBER OF LAAO PROCEDURES IN THE UNITED STATES*

23160

28197

33277

38839

44950

30,000

40,000

50,000

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18 49 141 364 1101 2455 41136310

873711686

1502618929

23160

0

10,000

20,000

*Entered into NCDR LAAO Registry

Price MJ for the NCDR LAAO steering committee, September 2019 San Francisco, CA

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CURRENT LAAC VOLUMES IN PERSPECTIVE RELATIVE TO THEBURDEN OF AF IN THE UNITED STATES

Total AF population

NV-AF (95%)

5 million patients

4.75 million patients

45,000 patients in NCDR LAAO Registry:

CHA2DS2VASC≥2

(75%)

OAC Intolerant (35%)



45,000 patients in NCDR LAAO Registry:3.6% of eligible population?

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transcatheter laa closure: why, when & in whomadherence to oac proportion of days covered 54.1...

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