Left Atrial Appendage Closure inAtrial Fibrillation to Prevent StrokeAtrial Fibrillation to Prevent Stroke

Matthew J. Price MDMatthew J. Price MDDirector, Cardiac Catheterization LaboratoryDirector, Cardiac Catheterization LaboratoryDirector, Cardiac Catheterization LaboratoryDirector, Cardiac Catheterization LaboratoryScripps ClinicScripps ClinicLa Jolla, CA, USALa Jolla, CA, USAprice.matthew@scrippshealth.orgprice.matthew@scrippshealth.org

SCRIPPS CLINIC

price.matthew@scrippshealth.orgprice.matthew@scrippshealth.org

Risk Factors for Stroke From TheRisk Factors for Stroke From ThePerspective of thePerspective of the 1717thth--CenturyCentury PhysicianPhysician

“To this variety of apoplexy those are most“To this variety of apoplexy those are most

Perspective of thePerspective of the 1717 --CenturyCentury PhysicianPhysician

“To this variety of apoplexy those are most“To this variety of apoplexy those are mostliable who lead an idle life, who are obese,liable who lead an idle life, who are obese,whose face and hands are constantly lividwhose face and hands are constantly lividwhose face and hands are constantly lividwhose face and hands are constantly lividandand whose pulse constantly unequalwhose pulse constantly unequal.”.”

Historiae ApoplecticorumJohann Jakob Wepfer, 1658Johann Jakob Wepfer, 1658

SCRIPPS CLINICApoplexy: Incapacity resulting from a cerebral hemorrhage or stroke.

Prevalence of Antithrombotic Therapies inPrevalence of Antithrombotic Therapies in AFAFPatients AcrossPatients Across the Spectrum of Strokethe Spectrum of Stroke Risk:Risk:Data from the NCDRData from the NCDR--PINNACLE RegistryPINNACLE RegistryData from the NCDRData from the NCDR--PINNACLE RegistryPINNACLE Registry

N=429,417

<50% of high-risk patientsget OACs

SCRIPPS CLINICHsu JC et al,Hsu JC et al, JAMAJAMA CardiolCardiol.. 2016;1(1):552016;1(1):55--6262

Effect of NOACs on Utilization of OAC inEffect of NOACs on Utilization of OAC inIndicated Population:Indicated Population: Data from the NCDRData from the NCDR--PINNACLE RegistryPINNACLE RegistryPINNACLE RegistryPINNACLE Registry

N=655,000N=655,000CHA2DS2VASC ≥2

SCRIPPS CLINICMarzecMarzec LN et al, JACC 2017; 69(20): 2475LN et al, JACC 2017; 69(20): 2475--24842484

OACs are Frequently DiscontinuedOACs are Frequently Discontinued

30%

50%

SCRIPPS CLINICMartinez et al, Thromb Haemost 2015

The NonThe Non--Vitamin K Oral AnticoagulantsVitamin K Oral Anticoagulants(NOACs):(NOACs): Clinical Trial SummaryClinical Trial Summary(NOACs):(NOACs): Clinical Trial SummaryClinical Trial Summary

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

DrugDrug DabigatranDabigatran RivoraxabanRivoraxaban ApixabanApixaban EdoxabanEdoxabanDrugDrug 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%TTR, controlTTR, control 67%67% 58%58% 66%66% 68%68%

IschemicIschemicstrokestroke

0.760.76 (0.60(0.60--0.98)0.98)

0.940.94 (0.75(0.75--1.17)1.17)

0.920.92 (0.74(0.74--1.14)1.14)

1.001.00 (0.83(0.83--1.19)1.19)

HemorrhagicHemorrhagic 0.260.26 (0.14(0.14-- 0.590.59 (0.37(0.37-- 0.510.51 (0.34(0.34-- 0.540.54 (0.38(0.38--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)mortalitymortality 1.00)1.00) 1.02)1.02) 0.998)0.998) 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-- 1.391.39 (1.19(1.19-- 0.890.89 (0.70(0.70-- 1.231.23 (1.02(1.02--

SCRIPPS CLINIC

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)

The Bad Actor:The Bad Actor: TheThe LeftLeft AtrialAtrial AppendageAppendageThe Bad Actor:The Bad Actor: TheThe LeftLeft AtrialAtrial AppendageAppendage

Why not a local therapy for a local problem?

• >90% of stroke-causing thrombus originates in the LAA

• Thromboembolic stroke from AF more debilitating – due to size of clots

SCRIPPS CLINICBlackshear J.L. Odell J.A., Annals of Thoracic Surgery, 1996;61:755-759

• Thromboembolic stroke from AF more debilitating – due to size of clots

A “Local” Approach to Stroke PreventionA “Local” Approach to Stroke PreventionA “Local” Approach to Stroke PreventionA “Local” Approach to Stroke Preventionin AF is Not A Novel Ideain AF is Not A Novel Idea

SCRIPPS CLINIC

LAALAA OccludersOccluders Clinically Available (CEClinically Available (CEMark or FDAMark or FDA--approved) or Currentlyapproved) or CurrentlyMark or FDAMark or FDA--approved) or Currentlyapproved) or CurrentlyUnder InvestigationUnder Investigation

U.S.U.S.: Watchman (FDA approved), Amulet (RCT),: Watchman (FDA approved), Amulet (RCT), U.S.U.S.: Watchman (FDA approved), Amulet (RCT),: Watchman (FDA approved), Amulet (RCT),WavecrestWavecrest (RCT soon)(RCT soon)

OUS:OUS:

•• WATCHMANWATCHMAN

•• AmplatzerAmplatzer AmuletAmulet•• AmplatzerAmplatzer AmuletAmulet

•• LifeTechLifeTech

•• OcclutechOcclutech•• OcclutechOcclutech

•• ProlipsisProlipsis

•• CardiaCardia

SCRIPPS CLINIC

•• AcroredisAcroredis

WATCHMAN LAAWATCHMAN LAA OccluderOccluderWATCHMAN LAAWATCHMAN LAA OccluderOccluder

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

diameterdiameter

NitinolNitinol FrameFrameNitinolNitinol FrameFrame•• 1010 active fixation anchorsactive fixation anchors --

designed to engage tissue fordesigned to engage tissue forstabilitystabilitystabilitystability

Proximal FaceProximal Face•• 160160 micron membrane PET capmicron membrane PET cap•• 160160 micron membrane PET capmicron membrane PET cap

designed to block emboli anddesigned to block emboli andpromote healingpromote healing

SCRIPPS CLINIC

Repositionable &Repositionable & rretreivableetreivable

Watchman LAA Closure at 1 Year FUWatchman LAA Closure at 1 Year FUWatchman LAA Closure at 1 Year FUWatchman LAA Closure at 1 Year FU

SCRIPPS CLINIC

WATCHMAN:WATCHMAN: FDAFDA IndicationsIndications for Usefor UseWATCHMAN:WATCHMAN: FDAFDA IndicationsIndications for Usefor Use

The WATCHMAN is indicatedThe WATCHMAN is indicated to reduce the risk ofto reduce the risk of The WATCHMAN is indicatedThe WATCHMAN is indicated to reduce the risk ofto reduce the risk ofthromboembolism from the LAAthromboembolism from the LAA in patients with AFin patients with AF who:who:

•• Are at increased risk for stroke and systemic embolismAre at increased risk for stroke and systemic embolismbased on CHADSbased on CHADS22 or CHAor CHA22DSDS22VASc scores and areVASc scores and arerecommended for anticoagulationrecommended for anticoagulation

•• Are deemed by their physicians to beAre deemed by their physicians to be suitable for warfarin;suitable for warfarin;•• Are deemed by their physicians to beAre deemed by their physicians to be suitable for warfarin;suitable for warfarin;andand

•• Have an appropriate rationaleHave an appropriate rationale to seek a nonto seek a non--•• Have an appropriate rationaleHave an appropriate rationale to seek a nonto seek a non--pharmacologic alternative to warfarin, taking into accountpharmacologic alternative to warfarin, taking into accountthe safety and effectiveness of the device compared withthe safety and effectiveness of the device compared with

SCRIPPS CLINIC

warfarin.warfarin.

ProspectiveProspective U.S. DatasetU.S. Dataset for WATCHMANfor WATCHMANLAA Closure in WarfarinLAA Closure in Warfarin--Eligible PatientsEligible PatientsLAA Closure in WarfarinLAA Closure in Warfarin--Eligible PatientsEligible Patients

Key Trials N Design

PROTECT AF(2005-2008)

707Prospective RCT - 2:1, non-inferiority trial of LAAclosure vs. warfarin.

CAP566

Prospective continuing access registry to gainCAP(2008-2010)

566Prospective continuing access registry to gainfurther information prior to PMA approval.

PREVAIL(2010-2012)

407Prospective RCT - 2:1, non-inferiority trial to collectadditional information on the WATCHMAN Device.(2010-2012) additional information on the WATCHMAN Device.

CAP2(2012-2014)

579Prospective continuing access registry prior toPMA approval.

Total patients >2,000 ~7,000 Patient-Years of Follow-up

ReddyReddy, et al. JAMA. 2014 ;312(19): 1988, et al. JAMA. 2014 ;312(19): 1988--19981998

SCRIPPS CLINIC

ReddyReddy, et al. JAMA. 2014 ;312(19): 1988, et al. JAMA. 2014 ;312(19): 1988--19981998Reddy VY et al. Circulation. 2011; 123:417Reddy VY et al. Circulation. 2011; 123:417--424424Holmes,Holmes, KarKar, Price MJ, Price MJ et al., JACCet al., JACC 2014,42014,4(1): 1(1): 1--1111

PostPost--procedural Adjunctiveprocedural AdjunctivePharmacotherapy in the WATCHMANPharmacotherapy in the WATCHMANPharmacotherapy in the WATCHMANPharmacotherapy in the WATCHMANClinical TrialsClinical Trials

SCRIPPS CLINICPrice MJ et al, JACCPrice MJ et al, JACC CardiovascCardiovasc IntervInterv 2015; 82015; 8:1925:1925--3232..

SCRIPPS CLINIC

PatientPatient--Level PROTECTLevel PROTECT AF/PREVAIL MetaAF/PREVAIL Meta--Analysis at 5 Years:Analysis at 5 Years: WATCHMAN LAACWATCHMAN LAACCompared With WarfarinCompared With Warfarin

HR p-value

Compared With WarfarinCompared With Warfarin

HR p-value

Efficacy 0.82 0.3

All stroke or SE 0.96 0.9All stroke or SE 0.96 0.9

Ischemic stroke or SE 1.7 0.08

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 0.04All-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)Reddy et al, JACC 2017Reddy et al, JACC 2017

PatientPatient--Level PROTECTLevel PROTECT AF/PREVAIL MetaAF/PREVAIL Meta--Analysis at 5 Years:Analysis at 5 Years: WATCHMAN LAACWATCHMAN LAACCompared With WarfarinCompared With Warfarin

HR p-value

Compared With WarfarinCompared With Warfarin

HR p-value

Efficacy 0.82 0.3

All stroke or SE 0.96 0.9All stroke or SE 0.96 0.9

Ischemic stroke or SE 1.7 0.08

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 0.04All-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)Reddy et al, JACC 2017Reddy et al, JACC 2017

PatientPatient--Level PROTECTLevel PROTECT AF/PREVAIL MetaAF/PREVAIL Meta--Analysis at 5 Years:Analysis at 5 Years: WATCHMAN LAACWATCHMAN LAACCompared With WarfarinCompared With Warfarin

HR p-value

Compared With WarfarinCompared With Warfarin

HR p-value

Efficacy 0.82 0.3

All stroke or SE 0.96 0.9All stroke or SE 0.96 0.9

Ischemic stroke or SE 1.7 0.08

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 0.04All-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)Reddy et al, JACC 2017Reddy et al, JACC 2017

PREVAIL: Rates of the ComponentPREVAIL: Rates of the ComponentEndpointsEndpointsEndpointsEndpoints

PREVAIL SubjectsPREVAIL Subjects

Device

(n=269)

Control

(n=138)

No. of Events Rate * No. of Events Rate * p-valueNo. of Events Rate * No. of Events Rate * p-value

2:1 RandomizationPrimary Efficacy:

Stroke/SE/CV Death37 / 1038.3 3.65 15 / 530.4 2.94 0.47

All Stroke 19 / 1042.4 1.97 7 / 530.4 1.29 0.32All Stroke 19 / 1042.4 1.97 7 / 530.4 1.29 0.32

Ischemic Stroke 17 / 1043.1 1.68 4 / 533.3 0.73 0.13

Hemorrhagic Stroke 2 / 1084.6 0.18 3 / 538.0 0.54 0.23Hemorrhagic Stroke 2 / 1084.6 0.18 3 / 538.0 0.54 0.23

Systemic Embolism 1 / 1080.6 0.09 0 / 540.9 n/a n/a

CV/Unexplained Death 18 / 1084.7 1.79 10 / 540.9 1.98 0.76

SCRIPPS CLINIC

Yearly stroke rate of 0.73 on warfarin in a population CHA2DS2VASc = 4.1 ±1.2!Wide confidence intervals, small # of patients

Comparative Stroke Rates BetweenComparative Stroke Rates BetweenWATCHMAN LAAC and Untreated AFWATCHMAN LAAC and Untreated AFWATCHMAN LAAC and Untreated AFWATCHMAN LAAC and Untreated AF

10

8

10Untreated AFTreated with WarfarinWATCHMAN Arm

6

IschemicStroke Risk(events per100 pt-yrs)

2

4

1.31.2

1.72.3

1.1

1.5

0

2PREVAIL

PROTECT AF

CAP2

CAPEWOLUTION

WASP

SCRIPPS CLINIC

01 2 3 4 5

PatientPatient--Level MetaLevel Meta--Analysis:Analysis: WATCHMANWATCHMANAssociated With SuperiorAssociated With Superior Reduction inReduction inDisabling StrokesDisabling Strokes

2.00% Disabling/Fatal Strokes Non-Disabling Strokes

Associated With SuperiorAssociated With Superior Reduction inReduction inDisabling StrokesDisabling Strokes

1.50%

2.00% Disabling/Fatal Strokes Non-Disabling Strokes

1.00%55%

Reduction

0.50%

Reduction

0.00%WATCHMAN warfarin

HR 0.45 (0.21 – 0.94)P=0.03

SCRIPPS CLINIC

Disabling Stroke defined as MRS ≥2Disabling Stroke defined as MRS ≥2

100

Free ofMajor 80

90

WATCHMANWarfarinMajor

BleedingEvent

(%)70

80 Warfarin

HR 0.28 [95% CI, 0.23 to 0.35]

(%)

60

Warfarin+Aspirin

Warfarin+Aspirin

Plavix+Aspirin Aspirin

72%Relative ReductionIn Major Bleeding

WATCHMANArm

SCRIPPS CLINIC6 6046 1808 45

500 7

+Aspirin +Aspirin +Aspirin AspirinArm

Price MJ et al, JACCPrice MJ et al, JACC CardiovascCardiovasc IntervInterv 2015; 82015; 8:1925:1925--3232..

EWOLUTION Registry:EWOLUTION Registry: SeriousSeriousProcedure/Device Related Events WithProcedure/Device Related Events WithProcedure/Device Related Events WithProcedure/Device Related Events WithWatchman LAA Closure Through 7 DaysWatchman LAA Closure Through 7 Days

N=1021

SCRIPPS CLINICBoersmaBoersma LV,LV, et al.et al. EurEur Heart JHeart J. 2016.. 2016.

Outcomes in the WATCHMAN PostOutcomes in the WATCHMAN Post--Approval Experience: N=3822Approval Experience: N=3822Approval Experience: N=3822Approval Experience: N=3822

  

  Post-FDA Approval Post-FDA Approval 

ExperienceExperience   ExperienceExperience

ComplicationsComplications   

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

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

Pericardial Effusion – No InterventionPericardial Effusion – No Intervention 11 (0.29%)11 (0.29%)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 Percutaneously     Removed Percutaneously 33

     Removed Surgically     Removed Surgically 66

DeathDeath   

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

SCRIPPS CLINIC

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

Holmes DR, JACC 2017Holmes DR, JACC 2017

ASAP-TOO Study DesignASAP-TOO Study DesignASAP-TOO Study DesignASAP-TOO Study Design

•• Prospective, randomized, multi-center, globalProspective, randomized, multi-center, global

•• Patients with Patients with non-valvular atrial fibrillation non-valvular atrial fibrillation deemed deemed not suitable for not suitable for oral anti-coagulation oral anti-coagulation therapytherapy to reduce the risk of stroke to reduce the risk of stroke..

•• Randomized 2:1 (Watchman vs Control)Randomized 2:1 (Watchman vs Control)•• Randomized 2:1 (Watchman vs Control)Randomized 2:1 (Watchman vs Control)

•• Considering Group Sequential DesignConsidering Group Sequential Design

•• Allows early looks; potential to stop early for benefitAllows early looks; potential to stop early for benefit

•• 888 subjects at up to 100 global sites888 subjects at up to 100 global sites•• 888 subjects at up to 100 global sites888 subjects at up to 100 global sites

•• Follow-Up*Follow-Up*

•• 45 Day with TEE45 Day with TEE•• 45 Day with TEE45 Day with TEE

•• 6,18 month phone visit6,18 month phone visit

•• 12 month with TEE12 month with TEE

•• Years 2-5 bi-annuallyYears 2-5 bi-annually

SCRIPPS CLINIC©2012 MFMER | slide-29

•• Years 2-5 bi-annuallyYears 2-5 bi-annually

* Brain imaging required at baseline if prior stroke or TIA* Brain imaging required at baseline if prior stroke or TIA

Watch-TAVR

Severe AS and AtrialFibrillation

N=400

Randomization

1:1

TAVR +Watchman

TAVR +

1:1

TAVR +Watchman Medical management

Primary endpointPrimary endpointDeath, Stroke and Major Bleeding

Investigator initiated, Co-PISamir Kapadia, Martin Leon

Cleveland Clinic

Samir Kapadia, Martin LeonSponsored by BSc

Decision Making Scheme for StrokeDecision Making Scheme for StrokePrevention Therapy in AFPrevention Therapy in AFPrevention Therapy in AFPrevention Therapy in AF

AF patient at highthromboembolic risk byCHA DS VASC scoreCHA2DS2VASC score

Low bleeding risk,Low bleeding risk,Not good candidate for long-term OAC(prior bleed, bleeding risk, on APT, non- Absolute or strongLow bleeding risk,Low bleeding risk,

compliant, canafford therapy

(prior bleed, bleeding risk, on APT, non-compliant, poor VKA candidate & can’t

afford/take NOAC) but can tolerateshort-term therapy

Absolute or strongcontraindication toeven short-term OAC

NOAC (or VKA)CommercialWatchman

ASAP-TOO

(WM vs notherapy)

Amulet vs.Watchman RCT

SCRIPPS CLINIC

Watchman RCT

The True Measure of SuccessThe True Measure of SuccessThe True Measure of SuccessThe True Measure of Success

Just finished FU TEE, told toJust finished FU TEE, told todiscontinue warfarin

Bruising from warfarin

SCRIPPS CLINIC

1 Week Later: Husband Can D/C1 Week Later: Husband Can D/CWarfarin…Warfarin…Time for a Dinner Date WithTime for a Dinner Date WithWarfarin…Warfarin…Time for a Dinner Date WithTime for a Dinner Date WithLots of Leafy Greens!!!Lots of Leafy Greens!!!

SCRIPPS CLINIC

Featuring livecasedemonstrations, hands-on workshopsand additional satellitesymposia!LAA Closure, TAVR, ASD/PFO, Mitral Repair, and More

A Pract ical ApproachFebruary 7-9, 2018 • San Diego Marriott La Jolla • La Jolla, California

Overview

Scripps Health’s Structural Heart Intervention

and Imaging conference is designed to provide

a practical, cutting-edge, case-based assessment

Course Directors

Matthew J. Price, MD, FACCDirector, Cardiac Catheterization LaboratoryScripps Clinic/Green Hospital

February 7-9, 2018 • San Diego Marriott La Jolla • La Jolla, California

a practical, cutting-edge, case-based assessment

of the emerging area of structural heart disease

intervention and interventional cardiovascular

imaging. The expert faculty will include inter-

ventionalists, invasive cardiologists, and echocar-

diographers. Faculty will discuss patient selection,

Scripps Clinic/Green HospitalAssistant ProfessorScripps Translational Science InstituteLa Jolla, California

David S. Rubenson, MD, FACC, FASEDirector, Cardiac Non-Invasive LaboratoryScripps Clinicdiographers. Faculty will discuss patient selection,

pre-procedural assessment, procedural tips, tech-

niques and challenges (including concurrent im-

aging) during the performance of the procedures,

and conclude with assessment of outcomes and

future directions.

Scripps ClinicLa Jolla, California

Contact UsScrippsConference Services& CME11025 North Torrey PinesRoad, Ste. 200

P: 858-652-5400E: med.edu@scrippshealth.org

SCRIPPS CLINIC

future directions. 11025 North Torrey PinesRoad, Ste. 200La Jolla, California 92037

E: med.edu@scrippshealth.orgW: www.scripps.org/conferenceservices