1 version 1, 2/21/02, draft medtronic insync ® icd cardiac resynchronization system fda advisory...

1Version 1, 2/21/02, DRAFT

Medtronic InSync® ICDCardiac Resynchronization System

FDA Advisory PanelMarch 5, 2002


Agenda

Background and Introduction Dr. William Abraham 10 minutes

Study Design and Methodology Dr. James Young 10 minutes

Safety and Lead Effectiveness Results

Dr. Angel Leon 20 minutes

Efficacy Results Dr. James Young 15 minutes

Comparison to InSync and Conclusions

Dr. William Abraham 10 minutes


Introduction and Background

William T. Abraham, MD


Introduction

• Over a third of moderate to severe heart failure patients (in NYHA Functional Class III or IV) have ventricular dysynchrony, evidenced by a QRS duration 130 ms1

• Associated with• Limited exercise tolerance• Impaired quality of life and functional capacity• Poor left ventricular systolic function2

1 Aaronson KD, et al. Circulation 1997; 95:2660-2667.2 Zardini M, et al. Eur Heart J 2000; 2(Suppl J): J16-J22


InSync Study Design

BaselineImplantAttempt

SuccessfulImplant

Control CRT

Pre-dischargeRandomization

1, 3, 6 Month

Follow-up

1, 3, 6 Month

Follow-up

CRT

DoubleBlinded

StableMedicalTherapy

1week

CRT

Long term follow up every 6 months

• Control: VDI mode

• Treatment (CRT): VDD mode


InSync Study Primary Endpoints*

Endpoint Control CRT p value

Quality of Life

(points)

9 18.5 0.003

NYHA Class 0 1 <0.001

6-minute walk

(meters)

10 40 0.003

* PMA# P010015, approved 8/28/01


InSync Study Secondary Clinical Endpoints

<0.00166,20,1442,35,23Composite Response (%)

<0.0018512Exercise Time

(sec)

0.0381.00.1Peak VO2

(ml/kg/min)

P valueCRTControlEndpoint


InSync Primary Safety Results Summary

Achieved all primary 6-month safety objectives including: Implant success

6-month device related complications attributed to:InSync Model 8040Attain Models 2187 and Model 2188 LV leadsInSync system

Attain Models 2187 and 2188 LV lead 6-month pacing threshold


InSyncDeath or Worsening Heart Failure Requiring

Hospitalization or IV Medications

50%

60%

70%

80%

90%

100%

0 1 2 3 4 5 6Months Since Implant

Fre

edo

m f

rom

Eve

nt

Rat

e

Hazard Ratio = 0.5895% CI (0.37,0.92)

73157162184211219230— CRT

62150157178197209231— Control

Patients At Risk

P = 0.02

CRT

Control


Model 7272 InSync ICD• Dual-chamber VT and VF detection• Antitachycardia (ATP) pacing,

cardioversion and defibrillation VT and VF therapies

• Simultaneous biventricular pacing• RV sensing only

Combining Resynchronization and ICD Function in a Single Device


Study Design, Methodology andPatient Population

James B. Young, MD


Entry Criteria

• Chronic heart failure

18 years of age

• NYHA Functional Class II, III or IV

• QRS duration 130 ms

• LVEF 35%

• LVEDD 55 millimeters (echo measure)

• Stable HF medical regimen for 1 month• ACE-I or substitute, if tolerated• β-blocker - stable regimen for 3 months

• Indication for an ICD


InSync ICD Study Design


SuccessfulImplant

Control CRT


1, 3, 6 Month

Follow-up

1, 3, 6 Month

Follow-up

CRT

DoubleBlinded


1week

CRT


• Control: DDI mode

• Treatment (CRT): DDD mode

• ICD active in all patients

• Heart failure medication stability maintained


Timing of Baseline Tests

Test InSync InSync ICD

6-Minute Hall Walk 0-7 days pre-implant

0-7 days pre-implant

Cardiopulmonary Exercise Test


0-7 days post-implant

QOL Questionnaire



NYHA 0-7 days pre-implant



Study Features to Maintain the Blind

• Blinded: • Patients (study ID card)

• Heart failure staff

• Listed on study blinding log

• Blinded to ECGs

• Conducted QOL, 6 minute hall walk, patients global assessment, NYHA classification and HF exam

• Events Classification Committee

• Unblinded:• EP staff

• Listed on study blinding log

• Viewed ECGs, device printouts, etc

• Data placed into secure study envelopes


Primary Safety Objectives

• InSync ICD-related complication-free survival at 3 months

• Attain Model 4189 LV lead-related complication-free survival at 6 months

• Attain Model 2187/2188 LV lead- related complication-free survival at 6 months

• InSync ICD system-related complication-free survival at 6 months


Secondary Safety Objectives

• Characterize patient survival

• Characterize complication events

• Characterize observation events


Lead Effectiveness Objectives

• Implant success• Evaluate the electrical performance of the

Model 4189 LV lead• Evaluate the electrical performance of the

Model 2187 and Model 2188 LV leads


Evaluation of Integrity of ICD Function

• Spontaneous VT/VF therapy effectiveness

• Comparison of VT/VF event rates in the control and treatment arms

• ATP therapy efficacy with biventricular pacing

• Implant ventricular defibrillation criterion


Primary Effectiveness Endpoints

• As pre-specified in the investigational plan for NYHA Class III and IV patients, the following change from baseline to 6-month visit between control and treatment groups in:

• Quality of life (MLWHF Questionnaire)• NYHA class• 6-minute hall walk distance

• As pre-specified in the investigational plan, all 3 endpoints must be met at P < 0.05, or 2 met at P < 0.025, or 1 met at P < 0.0167


Secondary Effectiveness Endpoints

Clinical endpoints

• Exercise performance

• Clinical composite response

• Health care utilization

Physiological variables

• Echocardiographic variables

• QRS duration

• Neurohormonal variables


Study Milestones

1999 2000 2001 2002

1st implantOctober 4, 1999

PMA submitted

May 3, 2001

100 NYHA Class III & IV

6-month visitsMarch, 2001

224 NYHA Class III & IV 6-month visitsOctober, 2001

PMA Update submittedNovember 9, 2001


Patient Disposition

Implant Attemptsn=636

Randomizedn=362

NYHA Class III/IVn=421

Controln=176

CRTn=186

NYHA Class IIn=215

Randomizedn=192

Controln=106

CRTn=86

As pre-specified in the I.P., data from NYHA Class III/IV

patients are discussed in this presentation


Patient Disposition

Implant Attemptsn=421

Unsuccessful Implants

n=50

Randomizedn=362

Not Randomizedn=9

Implant Successn=371

Controln=176

CRTn=186


Patient Disposition

Control n = 176 CRT n = 186

124 6 Month Dataset 133

35 Still in DB F/U 36

15 Death 12

2 6 month F/U Visit Missed 5


Methodology Overview

• Safety Data• As pre-specified in the investigational plan, data

from NYHA Class II, III and IV patients were submitted to FDA for the primary safety objectives

• At FDA’s request, safety data from NYHA Class III and IV patients only are included in the Panel Pack and in this presentation


Methodology Overview

• Efficacy Data• The investigational plan pre-specified that the primary

efficacy analysis was to be based on patients with paired data at 6 months, excluding crossovers

• Results presented are based on an intent-to-treat analysis for patients with paired data at 6 months, including crossovers

• Results of the pre-specified crossover excluded and last-observation-carried forward analyses will also be summarized


Controln=176

CRTn=186

Age, years (mean ± sd) 68 ± 9 67 11

Gender (% male) 77% 76%

NYHA (% Class III) 89% 88%

QRS duration, ms (mean ± sd) 162 ± 22 165 ± 22

LVEF, % (mean ± sd) 20 ± 6 21 ± 7

LVEDD, mm (mean ± sd) 71 ± 9 70 ± 9

Heart Failure Etiology (% ischemic) 74% 63%

Patient Demographics


Controln=176

CRTn=186

Peak VO2, ml/kg/min (mean ± sd) 13.5 ± 4.1 13.5 ± 3.7

6-Min Walk Distance, meters (mean ± sd) 247 ± 118 245 ± 127

Heart Rate, bpm (mean ± sd) 72 ± 13 71 ± 12

SBP, mmHg (mean ± sd) 111 ± 17 112 ± 20

DBP, mmHg (mean ± sd) 67 ± 13 66 ± 11

Diuretic Use 94% 93%

ACE-I or ARB Use 88% 91%

Beta-blocker Use 57% 63%

Patient Demographics


Safety Results

Angel R. Leon, MD


Primary Safety Objectives

• InSync ICD-related complication-free survival at 3 months

• Attain Model 4189 LV lead-related complication-free survival at 6 months

• Attain Model 2187/2188 LV lead- related complication-free survival at 6 months

• InSync ICD system-related complication-free survival at 6 months


Secondary Safety Objectives

• Characterize patient survival

• Characterize complication events

• Characterize observation events


Lead Effectiveness Objectives

• Implant success• Evaluate the electrical performance of the

Model 4189 LV lead• Evaluate the electrical performance of the

Model 2187 and Model 2188 LV leads


Evaluation of Integrity of ICD Function

• Spontaneous VT/VF therapy effectiveness

• Comparison of VT/VF event rates in the control and treatment arms

• ATP therapy efficacy with biventricular pacing

• Implant ventricular defibrillation criterion


Lead Placement and LV Venous Anatomy

A. Lateral (marginal) cardiac vein

B. Postero-lateral cardiac vein

C. Posterior cardiac vein

D. Middle cardiac vein

E. Great cardiac vein

E

D

ABC

Attain LV Model 4189• Transvenous, 4 French• Stylet/catheter Delivered• Unipolar


Adverse Event Definitions

• Complication: An adverse event requiring invasive intervention or that results in the death of or serious injury to the patient or in the termination of a significant device function

• Observation: An adverse event not requiring invasive intervention or resolves spontaneously

• System-related complication: A device-related complication that occurs after the initially implanted functioning system, comprised of: Model 7272 InSync ICD, a Model 4189, 2187 or 2188 LV lead, and RA and RV leads


Implant Success

Patient Implant Attemptsn=421

Unsuccessful Implants

n=50

Implant Successn=371

Implant success defined per the protocol as a successfully placed LV lead.


Unsuccessful Implants (n=50)

Reason* n

Dislodgement/unstable position 24

Unable to obtain distal location 18

Unable to cannulate coronary sinus ostium 16

Unacceptable pacing thresholds 13

Dissection/perforation 13

Unable to access coronary vein 8

Coronary vein too small 3

Patient decompensation during implant 3

Delivery system/tool problems 3

Patient venous anatomy 2

Diaphragmatic stimulation 2

Complete heart block 1

* Not mutually exclusive


Adverse Events During the Implant Procedure

371 Successful

Implants

(53 Events)

50 Unsuccessful

Implants

(26 Events)

Coronary Sinus Dissection 5 12

Heart Block 9 3

Pericardial Effusion 2 3

Ventricular Tachycardia 2 3

Atrial Fibrillation 4 0

Cardiac Perforation 3 2

Heart Failure Decompensation 3 0

Hypotension 2 1

Atrial Flutter 2 0

Events Occurring One Time 21 2


Resolution of Adverse Events During the Implant Procedure

Resolution*

371 Successful

Implants

(53 Events)

50 Unsuccessful

Implants

(26 Events)

No Intervention Required 11 9

Pharmacological Therapy 14 3

Reprogram Generator 6 0

Lead Repositioned 4 0

Lead Explanted 0 1

Other Treatment 31 16

*Categories not mutually exclusive.


Resolution of Implant Dissection/Perforation Events

432 implant attempts22 events (22 patients)

Events Patients

No Intervention 8 8

Procedure Abandoned 7 7

Pericardiocentesis 2 2

Hospitalized for observation 2 2

Echocardiogram 1 1

LV lead explanted / port plugged 1 1

Lead repositioned 1 1

No patient deaths related to these events.


Primary Safety Objective 1: Freedom From InSync ICD

Related Complications at 3 Months

50%

60%

70%

80%

90%

100%

0 1 2 3 4 5 6

Months Since Implant

Performance Objective• 371 patients implanted• 7 complications in 7 patients • Observed 3-month rate = 98.6%• Lower 95% confidence bound = 97.6%

• Performance objective: 95% LCB 89%


Freedom From InSync ICD Related Complications at 3 Months

371 patients implanted7 events (7 patients)

Events Patients

Pocket seroma/hematoma 2 2

Pain at pocket site 1 1

Abnormal impedance measurement 1 1

Dizziness 1 1

Electrical reset of ICD 1 1

Pocket infection 1 1


Primary Safety Objective 2: Freedom From Attain Model 4189

LV Lead-Related Complications at 6 Months

50%

60%

70%

80%

90%

100%

0 1 2 3 4 5 6


Performance Objective

• 315 patients implanted• 49 events (in 44 patients)• Observed 6-month rate = 85.1%• Lower 95% confidence bound = 81.7%• Performance objective: 95% LCB 75%


Freedom From Attain Model 4189 LV Lead-Related Complications at 6 Months


Events Patients*

Lead dislodgment 29 26

Extra cardiac stimulation 11 11

Elevated pacing thresholds 4 4

Failure to capture 3 3

Muscle stimulation – pectoral 1 1

Pericardial effusion 1 1

* Not mutually exclusive


Attain Model 4189 LV Lead Related Complication Event Resolution

Resolution* Events* Patients*

Lead repositioned 32 30

Lead replaced 10 10

Lead explanted 7 7

ICD reprogrammed 4 4

None, continue to follow 4 4

Pericardiocentesis 1 1

Extend/change lead route 1 1

Lead setscrew retightened 1 1

ICD replacement 1 1* Not mutually exclusive


Primary Safety Objective 3:Freedom From Attain Model 2187/2188

LV Lead-Related Complications at 6 Months


• 56 patients implanted • 5 events in 5 patients• Observed 6-month rate = 89.9%• Lower 95% confidence bound = 82.9%• Performance objective: 95% LCB 75%

50%

60%

70%

80%

90%

100%

0 1 2 3 4 5 6



Freedom From Attain Model 2187/2188 LV Lead-Related Complications at 6 Months


Events Patients

Lead dislodgment 3 3

Failure to capture 1 1

Elevated pacing thresholds 1 1


Primary Safety Objective 4:InSync ICD System-Related Complications at 6 Months

Events related to:

Left ventricular lead

Right atrial lead

54

11

InSync ICD 8

Right ventricular lead 4

System 2

50%

60%

70%

80%

90%

100%

0 1 2 3 4 5 6



• 371 patients implanted • 79 events in 65 patients• Observed 6 month rate = 81.1%• Lower 95% confidence bound = 77.6%• Performance objective: 95% LCB 67%


Primary Safety Results: Summary

All primary safety objectives satisfied Device-related complications attributed to:

InSync ICD Model 7272 Attain Models 4189, 2187 and 2188 leads InSync ICD system


Secondary Safety Results


Spontaneous VT/VF Therapy Effectiveness

Detection Zone

# Patients

# Episodes

# Successfully Terminated

# Unsuccessfully Terminated*

% Successfully Terminated

FVT 14 135 133 2 98.5%

VF 41 128 127 1 99.2%

VT 50 862 855 7 99.2%

Overall 78 1125 1115 10 99.1%

*

• VT terminated after all therapies were delivered (5 episodes)

• FVT/VT terminated after redetection but before additional therapies could be delivered (4 episodes)

• VF terminated after all therapies were delivered (1 episode)


VT/VF Episodes Control vs. CRTPatients Completing 6 Months of Follow-up

Control (n=116)

CRT (n=125)

Number of Patients with VT/VF (P=0.21)

29 (25.0%) 22 (17.6%)

Total Number of Episodes (P=0.15)

285 156

Episodes per Month 0.42 0.21


ATP Efficacy During Spontaneous VT

ATP Site

RV only RV + LV

Number of Episodes 294 523

Successfully Terminated with ATP (P<0.0001)

247 (84%) 493 (94%)


Ventricular Defibrillation Testing

Implant Criterion

Used

n Percent (% )

2 at 24 joules

295 79.5%

Binary Search

52 14.0%

Other 24 6.5%


Lead Effectiveness Results


Lead Effectiveness Objective 1:Implant Success Results

• Performance Objective: • Lower 95% Confidence Limit > 83%

• Results: • Observed rate: 371 successes / 421 attempts = 88.1%• Lower Limit of 2-Sided 95% C.I. = 84.6%

Implant success defined per the protocol as a successfully placed LV lead.


Lead Effectiveness Objective 2: Attain Model 4189

LV Lead Pacing Threshold Performance

Performance Objective:• The upper 95% confidence bound for the

mean pacing voltage threshold is < 3.0 Volts

Results:• Mean 6-month pacing threshold = 1.5 Volts

0.9 Volts• Upper limit of 2-sided 95% confidence

interval = 1.7 Volts


Voltage Pacing Threshold for Attain Model 4189 LV Leads

0.0

1.0

2.0

3.0

4.0

5.0

6.0

7.0

Pac

ing

Th

resh

old

at

0.5

ms

(vo

lts)


Implant PHD 1 Mo. 3 Mo. 6 Mo. 12 Mo. 18 Mo.

1.7 1.7 1.51.6 1.5 1.5 1.5

n=441 n=424 n=416 n=381 n=306 n=125 n=35


Lead Effectiveness Objective 3: Attain Model 2187/2188

LV Lead Pacing Threshold Performance

Performance Objective:• The upper 95% confidence bound for the

mean pacing voltage threshold is < 3.0 Volts

Results:• Mean 6-month pacing threshold = 1.9 Volts

1.0 Volts• Upper limit of 2-sided 95% confidence

interval = 2.2 Volts


Voltage Pacing Threshold for Attain Model 2187/2188 LV Leads

0.0

1.0

2.0

3.0

4.0

5.0

6.0

7.0

Pac

ing

Th

resh

old

at

0.5

ms

(vo

lts)


Implant PHD 1 Mo. 3 Mo. 6 Mo. 12 Mo. 18 Mo.

1.7 1.7 1.92.3 1.9 1.7 1.6

n=79 n=82 n=79 n=74 n=62 n=29 n=18


Effectiveness Results

James B. Young, MD


Primary Efficacy Endpoints

• QOL score• NYHA class• 6 minute hall walk distance

Change from baseline to 6-month follow up between control and treatment groups in:


Change in Quality of Life Score

10

20

30

40

50

60

70

80

Controln = 119

CRTn = 128

Baseline 6 Months

10

20

30

40

50

60

70

80

Base 1 M 3 M 6 M

Imp

rov

em

en

t

Control CRT

= -10 = -19

P=0.0098Score (Median)


Change in NYHA Functional Class

47% 48%

5%

63%

34%

3%

0%

10%

20%

30%

40%

50%

60%

70%

Improved Stayed the Same Worsened

Control (n=123)Treatment (n=131)

P=0.028


Change in NYHA Functional Class

6% 8%

38%

52%

90%

51%

90%

35%

10% 5% 10% 5%

0%

20%

40%

60%

80%

100%

Baseline 6-Months Baseline 6-Months

IVIIIIII

Control (n = 123) CRT (n = 131)


Change in 6-Minute Hall Walk Distance

150

200

250

300

350

400

450

Controln = 118

CRTn = 122

Baseline 6 Months

150

200

250

300

350

400

450

Base 1 M 3 M 6 M

Control CRT

= 53 = 56

P=0.408Distance Walked (Median)


Summary of Effect on Primary Endpoints

P-Values

EndpointIntention-to-Treat

Per Protocol

Intention-to-Treat Last Observation

Carried Forward

QOL 0.0098 0.0044 0.003

NYHA 0.028 0.0145 0.02

6 Minute Hall Walk 0.408 0.4993 0.25


Secondary Effectiveness Results


Secondary Effectiveness Endpoints

Clinical endpoints

• Exercise performance

• Clinical composite response

• Healthcare utilization

Physiological variables

• Echocardiographic variables

• QRS duration

• Plasma neurohormones


Secondary Effectiveness Results:Clinical Endpoints


Exercise PerformancePeak VO2 and Exercise Duration

Peak VO2 (ml/kg/min)

10

12

14

16

18

20

Baseline 6 Months

Controln = 93

CRTn = 96

= 0.0 = 1.1

P=0.05

Total Exercise Time (Seconds)

200

300

400

500

600

700

800

Controln = 96

CRTn = 97

= -26 = 58

P=<0.001


Clinical Composite Response - Definition

• ImprovedImproved NYHA class or global assessment

• WorsenedDeath; worsening heart failure leading to hospitalization or permanent withdrawal of therapy; or worsening of NYHA class or global assessment

• No Change

Packer et al. J Cardiac Failure 2001;7:176-182.


Clinical Composite Response Results

40%33%

26%26%

55%

19%

0%

10%

20%

30%

40%

50%

60%

70%

Improved No Change Worsened

Per

cent

age

of P

atie

nts

Control n=141 CRT n=150

P = 0.038


Hospitalization ResultsTotal Days Hospitalized Through 6 Months

573

703

0100200300400500600700

257

374

0

100

200

300

All-Cause Hospitalization* Heart Failure Hospitalization#

Control (n=176) CRT (n=186)

* Control Group: 134 hospitalizations (79 pts) CRT Group: 127 hospitalizations (75 pts)

# Control Group: 70 hospitalizations (47 pts) CRT Group: 54 hospitalizations (39 pts)

P = 0.18 P = 0.11


InSync ICDDeath or Worsening Heart Failure Requiring


50%

60%

70%

80%

90%

100%


Fre

edo

m f

rom

Eve

nt

Rat

e

Hazard Ratio = 0.6995% CI (0.46,1.04)

55102117137153170186— CRT

469396117137148176— Control

Patients At Risk

P = 0.07

CRT

Control


Secondary Effectiveness Results:Physiological Variables


Change in Echo Parameters

Control CRT P-value

LV End Diastolic Volume -5 -25 0.046

LV End Systolic Volume -8 -26 0.04

LV Ejection Fraction 1.6 3.0 0.06

Cardiac Index -0.02 0.03 0.89

Mitral regurgitation -0.5 -0.4 0.98

LV Inflow E Wave Max Velocity 0.5 -10.0 0.03

LV Inflow A Wave Max Velocity 6.5 -4.0 0.04


Change in Echo/ECG Parameters

Control CRT P-value

LV E-Wave/A-Wave Ratio -0.03 -0.06 0.82

Normalized LV Filling Time 0.01 0.05 0.001

LV Mass -6 -3 0.97

LV Diameter in Systole -0.3 -0.2 0.98

LV Diameter in Diastole -0.1 -0.3 0.85

Interventricular Mechanical Delay -2 -18 0.12

QRS Width -6 -20 0.01


Change in Neurohormone Levels

Control CRT P-value

Brain Natriuretic Peptide (BNP)

-3 -38 0.41

Dopamine 0.0 0.0 0.56

Norepinephrine -38.0 10.5 0.24

Epinephrine -4.0 0.0 0.03

Big Endothelin -0.5 -0.5 0.88


Comparison of InSync and InSync ICD

William T. Abraham, MD


InSync ICD Study Design


SuccessfulImplant

Control CRT


1, 3, 6 Month

Follow-up

1, 3, 6 Month

Follow-up

CRT

DoubleBlinded


1week

CRT


• Control: DDI mode

• Treatment (CRT): DDD mode

• ICD active in all patients

• Heart failure medication stability maintained


Timing of Baseline Tests

Test InSync InSync ICD

6-Minute Hall Walk 0-7 days pre-implant


Cardiopulmonary Exercise Test


0-7 days post-implant

QOL Questionnaire



NYHA 0-7 days pre-implant



InSync ICDn=362

InSyncn=532

Age, years (mean ± sd) 67 ± 10 64 11

Gender (% male) 77% 70%

NYHA (% Class III) 88% 90%

QRS duration, ms (mean ± sd) 164 ± 22 166 ± 21

LVEF, % (mean ± sd) 20 ± 7 22 ± 6

LVEDD, mm (mean ± sd) 71 ± 9 69 ± 10

Heart Failure Etiology (% ischemic) 69% 55%

Comparison of Patient Demographics – InSync and InSync ICD


InSync ICDn=362

InSyncn=532

Peak VO2 , ml/kg/min (mean ± sd) 13.5 ± 3.9 13.8 ± 3.7

6-MW Distance, meters (mean ± sd) 246 ± 123 298 ± 97

Heart Rate, bpm (mean ± sd) 71 ± 13 74 ± 13

SBP, mmHg (mean ± sd) 111 ± 18 112 ± 19

DBP, mmHg (mean ± sd) 66 ± 12 68 ± 11

Diuretic Use 93% 93%

ACE-I or ARB Use 90% 91%

Beta-blocker Use 60% 56%

Comparison of Patient Demographics – InSync and InSync ICD


Change in Quality of Life Score(InSync ICD vs. InSync)

P=0.010 P=0.003

InSyncInSync ICD

10

20

30

40

50

60

70

80

Base 1 M 3 M 6 M

Imp

rov

em

en

t

Control CRT

10

20

30

40

50

60

70

80

Base 1 M 3 M 6 M

Imp

rov

em

en

tControl CRT


P=0.02 P<0.001InSyncInSync ICD

Change in NYHA Class(InSync ICD vs. InSync)

47%63%

38%

68%

48%34%

59%

30%

3% 4% 2%5%

0%

20%

40%

60%

80%

100%

InSyncICD

Control

InSyncICD

Treatment

InSyncControl

InSyncTreatment

Worsened

Stayed theSame

Improved


Change in 6-Minute Hall Walk Distance (InSync ICD vs. InSync)

P=0.408 P=0.003InSyncInSync ICD

150

200

250

300

350

400

450

Base 1 M 3 M 6 M

Control CRT

150

200

250

300

350

400

450

Base 1 M 3 M 6 M

Control CRT


InSync and InSync ICD Studies:Primary Endpoints

0.003

0.408

+40

+56

+10

+53

6-minute walk

(meters)

<0.001

0.027

-1

-1

0

0

NYHA Class

(class)

0.003

0.010

-18.5

-19

-9

-10

Quality of Life

(points)

P-valueCRTControlEndpoint

White = InSync Study; Yellow = InSync ICD Study


InSync and InSync ICD Studies:Secondary Clinical Endpoints

<0.001

0.038

66,20,14

55,19,26

42,35,23

40,26,33

Composite Response (%)

<0.001

<0.001

85

58

12

-26

Exercise Time

(sec)

0.038

0.050

1.0

1.1

0.1

0.0

Peak VO2

(ml/kg/min)

P-valueCRTControlEndpoint

White = InSync Study; Yellow = InSync ICD Study


InSync ICDDeath or Worsening Heart Failure Requiring


50%

60%

70%

80%

90%

100%


Fre

edo

m f

rom

Eve

nt

Rat

e

Hazard Ratio = 0.6995% CI (0.46,1.04)

55102117137153170186— CRT

469396117137148176— Control

Patients At Risk

P = 0.07

CRT

Control


InSyncDeath or Worsening Heart Failure Requiring


50%

60%

70%

80%

90%

100%


Fre

edo

m f

rom

Eve

nt

Rat

e

Hazard Ratio = 0.5895% CI (0.37,0.92)

73157162184211219230— CRT

62150157178197209231— Control

Patients At Risk

P = 0.02

CRT

Control


Hospitalization Results: InSync ICDTotal Days Hospitalized Through 6 Months

573

703

0100200300400500600700

257

374

0

100

200

300



* Control Group: 134 hospitalizations (79 pts) CRT Group: 127 hospitalizations (75 pts)

# Control Group: 70 hospitalizations (47 pts) CRT Group: 54 hospitalizations (39 pts)

P = 0.18 P = 0.11


Hospitalization Results: InSyncTotal Days Hospitalized Through 6 Months

275

664

0100200300400500600700

56

302

050

100150200250300350



*Control Group: 99 hospitalizations (60 pts) CRT Group: 80 hospitalizations (57 pts)

#Control Group: 39 hospitalizations (27 pts) CRT Group: 20 hospitalizations (14 pts)

P=0.002 P=0.083


The End

1 version 1, 2/21/02, draft medtronic insync ® icd cardiac resynchronization system fda advisory...

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