packer cabana

3033548-1

Catheter Ablation vsCatheter Ablation vsAntiarrhythmic Drug Therapy for Antiarrhythmic Drug Therapy for Atrial Fibrillation: Results of the Atrial Fibrillation: Results of the

CABANA Pilot StudyCABANA Pilot Study

Douglas L. Packer, Kerry L. Lee, Daniel B. Mark, Kristi H. Monahan,Douglas L. Packer, Kerry L. Lee, Daniel B. Mark, Kristi H. Monahan,Kathleen L. Hoffmann, Gail E. Hafley, Jeanne E. Poole,Kathleen L. Hoffmann, Gail E. Hafley, Jeanne E. Poole,Tristram D. Bahnson, David J. Bradley, Richard Robb,Tristram D. Bahnson, David J. Bradley, Richard Robb,

Maryam Rettmann, David R. Holmes III, William Stevenson,Maryam Rettmann, David R. Holmes III, William Stevenson,John D. Hummel, Steven J. Bailin, John D. Day, Anil K. Bhandari,John D. Hummel, Steven J. Bailin, John D. Day, Anil K. Bhandari,

Francis Marchlinski, Neil Kay, Hugh Calkins, David J. WilberFrancis Marchlinski, Neil Kay, Hugh Calkins, David J. Wilber

ACC AtlantaACC AtlantaMarch 15, 2010March 15, 2010

3033548-2

Catheter Ablation vsCatheter Ablation vsAntiarrhythmic Drug Therapy for Antiarrhythmic Drug Therapy for Atrial Fibrillation: Results of the Atrial Fibrillation: Results of the

CABANA Pilot StudyCABANA Pilot Study

Research Relationships (DLP) with Biosense, Acuson, Siemens, Research Relationships (DLP) with Biosense, Acuson, Siemens, Cryocath, EPT, St. Jude, Cardiofocus, Symphony, Prorhythm, NIHCryocath, EPT, St. Jude, Cardiofocus, Symphony, Prorhythm, NIHRoyalties from IP licensed by St. Jude MedicalRoyalties from IP licensed by St. Jude MedicalUnpaid consulting relationships: Medtronic, Boston Scientific,Unpaid consulting relationships: Medtronic, Boston Scientific,St. Jude, Biosense, Siemens, CryocathSt. Jude, Biosense, Siemens, Cryocath

Other information available from Mayo CommunicationsOther information available from Mayo Communications

Funded by St. Jude Medical Foundation,Funded by St. Jude Medical Foundation,St. Paul, MinnesotaSt. Paul, Minnesota

3033548-4

Purpose of CABANA Pilot StudyPurpose of CABANA Pilot Study

• Determine the freedom from AF withDetermine the freedom from AF withablation vs drug therapy in patients withablation vs drug therapy in patients withmore problematic AF and accompanyingmore problematic AF and accompanyingco-morbiditiesco-morbidities

• Test the feasibility of a long-term pivotal trial Test the feasibility of a long-term pivotal trial for assessing mortality, stroke, hospitalization for assessing mortality, stroke, hospitalization and cost outcomesand cost outcomes

CABANA Pilot Study; ACC 2010CABANA Pilot Study; ACC 2010

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Design of the CABANA Pilot StudyDesign of the CABANA Pilot Study

2 paroxysmal AF episodes (2 paroxysmal AF episodes (1 1 hour) over 4 mos or hour) over 4 mos or >>1 persistent 1 persistent AF episode (>1 week)AF episode (>1 week)

65 yr of age, or <65 yr with 65 yr of age, or <65 yr with 1 1 risk factorsrisk factors

HypertensionHypertension

DiabetesDiabetes

Heart failureHeart failure

Prior CVA or TIAPrior CVA or TIA

LA size >5.0 cm (Vol In LA size >5.0 cm (Vol In 40 40 cc/mcc/m22))

EF EF 35 %35 %

• Eligible for ablation and Eligible for ablation and 2 2 rhythm control and/or rhythm control and/or 3 rate 3 rate control drugscontrol drugs

Atrial fibrillationAtrial fibrillationWarranting TherapyWarranting Therapy

Atrial fibrillationAtrial fibrillationWarranting TherapyWarranting Therapy

>>65 yr of age or65 yr of age or<65 yr with <65 yr with 1 CVA risk factor1 CVA risk factor

Eligible for ablation and/ or drug therapyEligible for ablation and/ or drug therapy

>>65 yr of age or65 yr of age or<65 yr with <65 yr with 1 CVA risk factor1 CVA risk factor

Eligible for ablation and/ or drug therapyEligible for ablation and/ or drug therapy

Drug Rx and ACDrug Rx and AC• Rate controlRate control• Rhythm RxRhythm Rx

Drug Rx and ACDrug Rx and AC• Rate controlRate control• Rhythm RxRhythm Rx

1° ablation & AC1° ablation & AC• PV isolationPV isolation• AdjunctiveAdjunctive

1° ablation & AC1° ablation & AC• PV isolationPV isolation• AdjunctiveAdjunctive

Follow-upFollow-up12 months12 monthsFollow-upFollow-up12 months12 months

RRRR


Inclusion Criteria

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CABANA Pilot StudyCABANA Pilot StudyBaseline Characteristics in 60 PatientsBaseline Characteristics in 60 Patients

Age (yrs)Age (yrs) 61±1061±10Age <65 yrs old with Age <65 yrs old with 2 risk factors2 risk factors 2525 66%66%Gender Male / Female (%) Gender Male / Female (%) 77%77% 23%23%

Hypertension (%)Hypertension (%) 4848 80%80%Diabetes (%)Diabetes (%) 1111 18%18%CAD (%)CAD (%) 2121 35%35%Prior MI (%)Prior MI (%) 6 6 10%10%Prior CABG/PTCA (%) Prior CABG/PTCA (%) 1313 22%22%Dilated cardiomyopathy (%)Dilated cardiomyopathy (%) 1010 17%17%Congestive heart failureCongestive heart failure 1313 22%22%

Ejection fraction (%)Ejection fraction (%) 55 ± 1055 ± 10LA size (mm)LA size (mm) 4.4±1.04.4±1.0Left atrial enlargementLeft atrial enlargement

None (%)None (%) 8 8 16%16%Mild–moderate (%)Mild–moderate (%) 27 27 54%54%Severe (%)Severe (%) 15 15 30%30%

CHADS2 scoreCHADS2 score11 36 36 61%61%2 2 23 23 39%39%


QuickTime™ and a decompressor

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CABANA Pilot StudyCABANA Pilot StudyArrhythmia HistoryArrhythmia History

Type of AFType of AF ParoxysmalParoxysmal 19 32%19 32% Persistent Persistent 22 37%22 37% Long standing persistentLong standing persistent 19 32%19 32%

Years since first AF episode (yrs)Years since first AF episode (yrs) 3.3±4.6 3.3±4.6

CCS AF severityCCS AF severity Class 1-2 Class 1-2 18 32%18 32% Class 3-4 Class 3-4 35 61%35 61%Prior anti-arrhythmic drugs (no.)Prior anti-arrhythmic drugs (no.) 0 0 42 70%42 70% 1 1 15 25%15 25% 2 2 3 5% 3 5%Hospitalized for AFHospitalized for AF 28 47%28 47%Direct current cardio-versionDirect current cardio-version 32 53%32 53%

History of atrial flutterHistory of atrial flutter 14 23%14 23%




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CABANA Pilot StudyCABANA Pilot StudyTreatmentTreatment

%%

Drug TherapyDrug Therapyn=31n=31

RateRate

100

80

60

40

20

0RhythmRhythm Rate &Rate &

rhythmrhythm

AblationAblationn=29n=29

PVPVisolationisolation

WACA/WACA/antralantral

isolationisolation

LinearLinearAblAbl

CFAECFAE GPGP

%%

100

80

60

40

20

0

n=1346%

n=2589%

n=1138%

n=621%

n=14%

4 13%

5 16%

2271%

29 (100)




3033548-9

CABANA Pilot StudyCABANA Pilot StudyFirst Post-Blanking AF Event Over Follow-upFirst Post-Blanking AF Event Over Follow-up

11sts

t AF

ep

iso

de

(%)

AF

ep

iso

de

(%)

MonthsMonths3-63-6 6-96-9 9-129-12

n=16 n=16 52%52%

n=7 n=7 24%24%

n=3 n=3 10%10%

n=3 n=3 10%10% n=1 n=1

3%3%

n=4 n=4 14%14%

Drug (n=31)Drug (n=31)

Ablation (n=29)Ablation (n=29)




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0

20

40

60

80

100

0 3 6 9 12

Freedom from Recurrence of Freedom from Recurrence of SymptomaticSymptomatic Atrial Fibrillation Post Blanking PeriodAtrial Fibrillation Post Blanking Period

Fre

edo

m f

rom

AF

Fre

edo

m f

rom

AF

recu

rren

cere

curr

ence

Time (months)Time (months)

AblationAblation

Drug RxDrug Rx

HR 0.42 (0.19-0.95) P=0.033HR 0.42 (0.19-0.95) P=0.033

BlankingBlankingperiod*period*

24%24%

11 2828 2727 2323 2020 7722 3131 3030 1616 1313 77

65%65%

41%41%

3033548-11

0

20

40

60

80

100

0 3 6 9 12

Freedom from Recurrence of Freedom from Recurrence of Any Any SymptomaticSymptomatic AF, AFL, or AT AF, AFL, or AT

11 2828 2727 2222 1919 7722 3131 3030 1616 1212 66

Fre

edo

m f

rom

AF

/AF

L/

Fre

edo

m f

rom

AF

/AF

L/

AT

rec

urr

ence

AT

rec

urr

ence

Months since treatment startMonths since treatment start

AblationAblation

Drug RxDrug Rx

HR 0.46 (0.21-0.99) P=0.042HR 0.46 (0.21-0.99) P=0.042

BlankingBlankingperiod*period*

61%61%

38%38%

23%23%

3033548-12CABANA Pilot Study; ACC 2010CABANA Pilot Study; ACC 2010

CABANA Pilot StudyCABANA Pilot StudyCross-Overs and Redo TherapyCross-Overs and Redo Therapy

*2 failed Ic; 2 failed IIIs*2 failed Ic; 2 failed IIIs

0

10

20

30

CrossoverCrossoverto Ablto Abl

AA RxAA Rx

n=6 n=6 21%21%

Drug RxDrug Rxn=31n=31

n=4 n=4 13%*13%*

n=8 28%n=8 28%

Ablation RxAblation Rxn=29n=29

PtPt(%)(%)

Re-ablationRe-ablation



3033548-13

Maintenance of Sinus Rhythm Maintenance of Sinus Rhythm in CABANA Pilot at 12 Monthsin CABANA Pilot at 12 Months

No AFNo AFon Rxon Rx

AAD RxAAD Rxn=18n=18

No AFNo AFNo drugNo drug

No AFNo AFLate offLate off

drugdrug

No AFNo AFon drugon drug

Non AFNon AFwith redowith redo

n=5n=5

Ablation RxAblation Rxn=29n=29

n=13n=13n=15n=15

n=17n=17 n=17n=17

+2 pt+2 pt +0 pt




3033548-14

0.0

0.2

0.4

0.6

0.8

1.0

0 3 6 9 12

CABANA Pilot StudyCABANA Pilot StudyRecurrence of Recurrence of AnyAny AF, AFL, or AT AF, AFL, or AT

AF

/AF

L/A

T r

ecu

rren

ce (

%)

AF

/AF

L/A

T r

ecu

rren

ce (

%)

Time (months)Time (months)Ablation RxAblation Rx 2929 2626 1818 1414 44Drug RxDrug Rx 3131 3030 1212 8 8 55


DrugDrug

AblationAblation

HR 0.69 (0.37-1.32) P=0.264HR 0.69 (0.37-1.32) P=0.264

(36)(36)

(72)(72)

(50)(50)

72%72%

66%66%(59)(59)

BlankingBlankingperiodperiod



3033548-16

CABANA Pilot StudyCABANA Pilot StudyPerception of Atrial FibrillationPerception of Atrial Fibrillation

61

8

29

64

4

13

0

20

40

60

80

100

BaselineBaseline 3 mo3 mo 12 mo12 mo

Pat

ien

ts (

%)

Pat

ien

ts (

%)

Drug (n=31)Drug (n=31)

Ablation (n=29)Ablation (n=29)




3033548-17

Adverse Events in the CABANA Pilot StudyAdverse Events in the CABANA Pilot StudyAblationAblation Drug RxDrug Rx

n=29n=29 n=31n=31DVT (%)DVT (%) 1 (3.4) 1 (3.4)AV fistula/pseudo aneurysm (%)AV fistula/pseudo aneurysm (%) 2 (6.8) 2 (6.8)CVA/TIA (%)CVA/TIA (%) 1 (3.4) 1 (3.4)PV stenosisPV stenosis

Moderate (50-75%)Moderate (50-75%) 1 (3.4) 1 (3.4)Severe (75-95%)Severe (75-95%) 0 (0)0 (0)

Atrial esophageal fistula (%)Atrial esophageal fistula (%) 0 (0)0 (0)Tamponade (%)Tamponade (%) 1 (3.4) 1 (3.4)Congestive heart failure (%)Congestive heart failure (%) 3 (10.2) 3 (10.2) 1 (3.2) 1 (3.2)Volume overload (%)Volume overload (%) 2 (6.8) 2 (6.8) 0 (0)0 (0)Myocardial infarction (%)Myocardial infarction (%) 1 (3.4) 1 (3.4) 0 (0)0 (0)Bradycardia (%)Bradycardia (%) 1 (3.4) 1 (3.4) 0 (0)0 (0)Ventricular tachycardia (%)Ventricular tachycardia (%) 0 (0)0 (0) 1 (3.2) 1 (3.2)Atrial flutter (%)Atrial flutter (%) 0 (0)0 (0) 1 (3.2) 1 (3.2)LFT increase (%)LFT increase (%) 0 (0)0 (0) 1 (3.2) 1 (3.2)UTI (%)UTI (%) 1 (3.4) 1 (3.4) 0 (0)0 (0)Death, Cardiac Arrest, CVADeath, Cardiac Arrest, CVA 0 (0)0 (0) 0 (0)0 (0)


3033548-18

LimitationsLimitations

• Limited number of subjects in this Limited number of subjects in this pilotpilot study study

• Follow-up was limited to 12 monthsFollow-up was limited to 12 months

• As expected a small number of patients crossed As expected a small number of patients crossed over from drug to ablative therapyover from drug to ablative therapy

• Small numbers of at risk patients at 12 months Small numbers of at risk patients at 12 months limiting “late” conclusion that can be drawnlimiting “late” conclusion that can be drawn


3033548-19

Conclusion of the CABANA Pilot StudyConclusion of the CABANA Pilot Study

• Ablative intervention was more effective than drug Ablative intervention was more effective than drug therapy for preventing recurrent therapy for preventing recurrent symptomaticsymptomatic atrial atrial fibrillationfibrillation

• Treatment success rates in this population, which Treatment success rates in this population, which include a significant percentage with persistent and include a significant percentage with persistent and long-standing persistent AF, were lower than long-standing persistent AF, were lower than observed in other randomized clinical trialsobserved in other randomized clinical trials

• Late recurrence of AF may reduce long-term Late recurrence of AF may reduce long-term effectiveness of ablationeffectiveness of ablation

• This pilot study establishes the feasibility and This pilot study establishes the feasibility and importance of conducting a pivotal trial for importance of conducting a pivotal trial for establishing long-term outcome, mortality, quality of establishing long-term outcome, mortality, quality of life, and cost of therapy for AFlife, and cost of therapy for AF


3033548-20

CABANA Pilot SitesCABANA Pilot Sites

• Mayo ClinicMayo Clinic Doug PackerDoug Packer

• Loyola UniversityLoyola University Dave WilberDave Wilber

• Mercy Med/Des MoinesMercy Med/Des Moines Steve BailinSteve Bailin

• Ohio StateOhio State John HummelJohn Hummel

• Intermountain Med CenterIntermountain Med Center Crandall/DayCrandall/Day

• Good SamaritanGood Samaritan Anil BhandariAnil Bhandari

• University of AlabamaUniversity of Alabama Neal KayNeal Kay

• Mass General BostonMass General Boston Reddy/RuskinReddy/Ruskin

• Johns HopkinsJohns Hopkins Hugh CalkinsHugh Calkins

• Brigham and WomensBrigham and Womens Bill StevensonBill Stevenson

• University of PennsylvaniaUniversity of PennsylvaniaCallans/MarchlinskiCallans/MarchlinskiEnrolled: 60 of 60 patientsEnrolled: 60 of 60 patients




3033548-21

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CABANA Pilot StudyCABANA Pilot StudyTime to Treatment InitiationTime to Treatment Initiation

Drugn=31

Ablationn=28

Randomization

To ablation

To Rx

5 (1,15)

Blanking 90 daysBlanking 90 days

Blanking 90 daysBlanking 90 days

23 (17,42)


Time



3033548-23

CABANA Pilot StudyCABANA Pilot StudyChange in LA Size in Ablated PatientsChange in LA Size in Ablated Patients

BaselineBaseline 3 mo3 mo ChangeChange

VolumeVolume

BaselineBaseline 3 mo3 mo ChangeChange

Volume indexVolume index


3033548-24



packer cabana

Documents

pilot research

cabana pilot study douglas

purpose of cabana pilot

mayo clinic

jude medical foundation

ablation vs drug therapy

mayo communications

avw technology