AMPLATZER™ Left Atrial Appendage data...

Modern aspects in multidisciplinarythromboembolic prophylaxis

AMPLATZER™ Left Atrial Appendage data update

Igal Moarof, MD

Interventional Cardiology

Kantonsspital Aarau

Potential conflicts of interest

Speaker’s name: Igal Moarof

▪ I have the following potential conflicts of interest to report:

▪ Consultant for SJM / Abbott

Amulet Global

Observational Study4

N = 1088

AMPLATZER™ left atrial appendage

occlusion Clinical Data

1. Park, J. W., et al. (2011). LAA closure with AMPLATZER Cardiac Plug in atrial fibrillation - initial European experience. Catheterization and Cardiovascular Interventions, 77(5), 700-706.

2. Walsh, K. (2012, May). LAA closure with the AMPLATZER cardiac plug: results of the European post-market observational study. Presented at EuroPCR 2012, Paris.

3. Tzikas, A., et al. (2016). LAA occlusion for stroke prevention in atrial fibrillation: multicentre experience with the AMPLATZER Cardiac Plug. EuroIntervention, 11(10), 1170-1179

4. Landmesser, U. et al.. 2017. LAA occlusion with the AMPLATZER Amulet device: periprocedural and early clinical/echocardiographic data from a global prospective observational study. EuroIntervention 2017;13-online publish-ahead-of-print June 2017

AMPLATZER™ Amulet™ IDE

LAA Occluder RCT

N = >1600 (ongoing)

ACP Multicenter experience³

N = 1047

ACP EU Prospective

Observational Study²

N = 204

ACP Initial EU

Registry¹

N = 137

Physician-Driven Published Real-World Data

N = > 200 published papers (Pubmed search)

2008 2009 2010 2011 2012 2013 2014 2015 2016 2017 2018

Single-arm multicenter clinical evaluation of ACP for stroke prevention in AF pts.

Multicenter Study Experience With the

AMPLATZER™ Cardiac plug

Tzikas, A. et al. (2016). Left atrial appendage occlusion for stroke prevention in atrial fibrillation: multicentre experience with the AMPLATZER Cardiac Plug. EuroIntervention, 11(10), 1170-1179.

Total patients 1,047

Number of centers 22

Patient years follow-up 1,349

CHA2DS2-VASc (Mean) 4.5

HAS-BLED (Mean) 3.1

Age (Mean) 74.9

Prior stroke / TIA 37%

Previous major bleeding 47%

Taking OAC at time of implant 29.5%

Concomitant procedures to LAAO 20.6%

Multicenter Study Experience with the AMPLATZER™ Cardiac Plug

Indication for LAAO in more than 1,000 patients:

8%

9%

14%

15%

16%

17%

22%

35%

47%

0% 5% 10% 15% 20% 25% 30% 35% 40% 45% 50%

Risk of falls

Labile INR

Renal or hepatic disease

Previous minor bleeding

Stroke on Warfarin

Drug Interaction

CAD and stenting

High bleed risk

Previous major bleeding


Multicenter Study Experience With the

AMPLATZER™ Cardiac Plug1

5,62%

2,30%

0%

2%

4%

6%

Total PatientsTotal Patient

Years

CHA2DS2-VASc

Score

1001 1349 4.43

Estimated Stroke Rate

per CHA2DS2-VASc

Actual Annual Stroke

Rate

(N strokes + TIA)

5.62% 2.30% (31)

5,34%

2,08%

0%

2%

4%

6%

Total PatientsTotal Patient

Years

HAS-BLED

Score

1001 1349 3.12

Estimated Bleeding Rate

per HAS-BLED

Actual Annual Bleeding

Rate

(N major bleeds)

5.34% 2.08% (28)

-59% - 61%

Estimated based on CHA2DS2-VASc score

Observed rate in study

Estimated based on HAS-BLED score

Observed rate in study

Effectiveness in Stroke Reduction vs. Estimated

Effectiveness in Bleeding Reduction vs. Estimated


4

5,08

9,6

5,9

5,3

7,7

6,7

5,62 5,8

7,7

8,6

1,98 2,14 2,4 2,3 0 2,5 3,2 2,3 2,3 2,2 2,90

2

4

6

8

10

Walsh Kefer Lopez-Minguez

Urena Chun Santoro Kebernik Tzikas Korsholm Berti Berti -2

TE

ra

te [

eve

nts

/ye

ar]

Expected*

Observed

68%61%

7

Expected and observed stroke rates in

AMPLATZER™ LAA Occluders

1. Walsh et al. Presented at EuroPCR, Paris. 2012 2. Kefer, J. et al. Acta Cardiolog. 201368(6); 551-558 3. López-Mínguez et al. Heart. 2015;101:877–883. 4. Urena et al. JACC Cardiovascular Interventions, 2013. 62, 96-102.

5.Chun et al. Heart Rhythm, 2013 10, 1792-1799. 6. Santoro et al. EuroIntervention, 2016. 11(10), 1188-1194 7. Kebernik et al. Cardiology and Therapy, 2015. 4(2), 167-177. 8. Tzikas et al. EuroIntervention, 2016. 11(10), 1170-1179.

9. Korsholm et al. EuroIntervention. 2017;12:2075-2082. 10 Berti et al. Heart. 2016;102:1969-1973. 11. Berti et al., Int J Cardiol. 2017 Jul 16. pii: S0167-5273(17).

* Expected stroke rates are based on the patients CHADS2 or CHA2DS2VASc scores.

Patients 204 75 158 52 40 128 89 1001 107 110 542

Patient years 101 75 290 87 NR 238 93 1349 265 264 896

Strokes/TIAs 2 2 7 2 0 5 3 31 6 6 16

TEreduction [%] 51% 58% 75% 61% N/A 68% 52% 59% 61% 71% 66%

51%58%

61%

58%

58%75% 59%

52%

71%

66%

1 2 3 4 5 6 7 8 109 11

Reported by Nietlispach¹

Park²

(Multi)

Berti³

(Italian)

Walsh4

(Multiple)

Santoro5

(Spain)

Tzikas6

(Multiple)

Lopez-

Minguez7

(Spain)

Meerkin8

(Israel)

Betts9

(UK)

Berti (2)10

(Italian)

Nielsen-

Kudsk 11

(Nordic)

Enrollment period 2008 12/2008–

12/2009

1/2009–

4/2013

8/2009 –

9/2011

1/2009 –

12/2012

12/2008 –

11/2013

3/2009 –

2013

NR 7/2009 –

11/2014

12/2008-

4/2015

2009 –

2/2015

CHADS2

CHA2DS2-VASc

NR

3.7

NR NR

4.4

2.6

-

NR

4 (median)

2.8

4.5

3 (median)

4 (median)

3.2

-

2.63 ± 1.24

4.22 ± 1.56

-

4.2 ± 1.5

NR

3.9

Patients enrolled 120 143 121 204 134 1047 167 100 125 613 176

Successful device

implantation

117

(97.5%)

132

(96.4%)

117

(96.7%)

197

(96.6%)

128

(95.5%)

1019

(97.3%)

158

(94.6%)

100

(100%)

119

(95.2%)

585

(95.4%)

172

(97.2%)

Major peri-procedural

complications

▪ Stroke/TIA

▪ MI / air embolism

▪ Device embolization

▪ Major

tamponade/effusion

▪ Major bleeding

▪ Other

7 (5.8%)

3

0

2

2

0

0

10

(7.3%)

3

0

2

5

0

0

4 (3.3%)

1

0

0

3

0

0

6 (2.9%)

0

0

3

3

0

0

4 (3.0%)

1

0

0

3

0

0

52 (4.97%)

9

1

8

13

13

8

9 (5.4%)

2

0

1

2

0

4

1 (1.0%)

0

0

0

1

0

0

6 (4.8%)

2

0

2

2

0

0

38 (6.2%)

4

0

1

12

20

1

7 (4.0%)

0

0

1

1

2

3

Procedural success and safety with AMPLATZER™ Cardiac Plug

>100 patients*

• Procedures carried out according to IFU with Echocardiography and fluoroscopy.

1.Nietlispach et al. Cath and Card Int., 2013. 82, 283-289. 2. Park et al. Cath.and Card.Int., 2011. 77(5), 700-706. 3. Berti et al. J.American College of Cardiology: Card. Int. 2014. 7, 1036-1044. 4. Walsh et al. Presented at EuroPCR 2012, Paris.

5. Santoro et al. EuroIntervention, 2016. 11(10), 1188-1194. 6. Tzikas et al. EuroIntervention, 2016. 11(10), 1170-1179 7. López-Minguez et al. Heart, 2015.101, 877-883. 8. Meerkin et al. International Journal of Cardiology, 2013. 168, 3920-39259.

9. Betts et al. Catheter Cardiovasc Interv. 2016 Sep 21. [Epub ahead of print] 10. Berti et al. Int J Cardiol. 2017 Jul 16. [Epub ahead of print] 11. Nielsen-Kudsk et al. EuroIntervention. 2017 Jun 20;13(3):371-378. doi: 10.4244/EIJ-D-17-00201.

All studies include learning curve – increased success rates and reduced

complication rates with increasing operator experience.

AMPLATZER™ Amulet™ Device Multicentre prospective real-world observational study

Procedural and up to 3 month follow up

Landmesser, U.,et al. EuroIntervention 2017;13-online publish-ahead-of-print June 2017

Study and patient characteristics

Enrollment 1,088 (61 centers, enrolled between June 2015 and September 2016)

Age 75±8.5 years

CHA2DS2-VASc 4.2±1.6 (64.9% CHA2DS2-VASc score ≥4)

HASBLED 3.3±1.1

(77.1% HAS-BLED score ≥3)

Follow up 2.4±0.8 months.

Indication 82.8% absolute or relative contraindication to LT OAC

72.4% previous major bleeding

General

Anaesthesia

56.5%



Results

Successful implantation 99%

Closure < 3mm (follow up) 98.2%

First device choice 93.9%

99,6%98,2%

0%

50%

100%

LAA Closure (Implant) LAA Closure (1-3Month Visit)

LAA Closure Rates


• LAA closure defined by an independent echo core lab as

• absence of peri-device flow –or-• flow of < 3 mm jet into the LAA

• Implanting centers reported:

99.7% at implant and 99.4% at 3 months of

patients had no leak or < 5mm.


During Procedure and Index Hospitalization (CEC Adjudicated)

Results

Major AE 3.2%

Major bleeding:

Pericardial effusion/tamponade

Pericardiocentesis

Surgery

2.4%

(1.2%)

(0.9%)

(0.3%)

Vascular complications 0.9%

Death –

1 cardiac perforation

1 cardiorespiratory arrest/shock

0.2%

Device embolization 0.1%


AMPLATZER™ Amulet™ DeviceMulticentre prospective real-world observational study


Post procedural medication (discharge)

Single antiplatelet 23%

Dual antiplatelet 54.3%

Oral anticoagulation 18.9%

No antithrombotic therapy 2%

Device Associated Thrombus:

• Ten (10) cases of device on thrombus were reported through 90 days of implant.

• Represents 0.9% device on thrombus rate within 90 days of implants in all implanted patients in the study. (10 out of 1077 implant attempts)

• Represent 1.5% (10 out of 673 echoes adjudicated by core lab)

• One patient had an ischemic stroke 28 days after detection of device thrombus.


Study Freixa1 Cruz² Abualsaud³ Bartoletti4 Karczewski5 Kleinecke6 Landmesser7 Aguirre8

Enrollment period 7/2012 -

6/2013

10 – 12

2014

11/2009 –

6/2012

8/2014 –

11/2015

NA 10/2014 –

8/2015

6/2015 –

9/2016

6-9/2016

Mean

stroke

risk

CHADS2

CHA2DS2-VASc

NA

4.3 ±1.7

NA

4.9 ± 1.3

3.2

4.1

NA

4(median)

3

5

NA

5.2 ± 1.8

NA

4.2±1.6

3.8 ± 1.1

NA

LAA occlusion attempted 25 20 31 39 34 50 1088 22

Successful device

implantation

24

(96%)

20

(100%)

31

(100%)

39

(100%)

34

(100%)

49

(98%)

1077

(99%)

22

(100%)

Major peri-procedural

complications

▪ Stroke

▪ TIA

▪ MI / coronary air embolism

▪ Device embolization

▪ Major tamponade//effusion

▪ Major bleeding

▪ Other

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

2

0

0

0

0

0

2

0

1

0

0

0

0

1

0

0

4

0

0

0

1

2

01(retropharyngea

l hematoma)

41

2

0

0

1

13

132 deaths

(perforation and

cardiac arrest)

0

0

0

0

0

0

0

0

Minor peri-procedural

complications

0 0 0 0 3 (vascular) 5 ( vascular) 10 (vascular) 0

LAA closure success

(% < 3mm leak)

2-3 mths:

100%

60 days:

100%

Mean 1.4

mths:

96%

Mean 189 ±119 days

91.6%2 pts<5mm leak)

6 mths:

100%

6 weeks:

100%

Mean 2.4±0.8

mths: 98.2%

30 days:

100%

<5mm

Procedural success and safety of AMPLATZER™ Amulet™ LAA occluder

>20 patients*

Procedures performed with recommended echocardiographic and fluoroscopic Guidance

1. Freixa X, et al. Int J Cardiol. 2014 Jul 1;174(3):492-6. 2. Cruz-González, I. et al. Revista Española de Cardiología, 2015. 68, 724-726. 3. Abualsaud, A. et al. J.Inv. Card., 2016. 28, 34-38. 4. Bartoletti,S. et al. Heart 2016;102:A45-A46.

5. Karczewski M. et al. Kardiochir Torakochirurgia Pol. 2016 Jun;13(2):98-104 6. Kleinecke C, et al. Cardiol J. 2017 Feb 15. [Epub ahead of print] 7. Landmesser, U.,et al. EuroIntervention 2017;13-online publish-ahead-of-print June 2017

8. Aguirre et al. Catheter Cardiovasc Interv. 2017 Aug 24. [Epub ahead of print]

• At 12 month follow up 26% patients were without any ASA or antithrombotic medication

• Conclusion – Aspirin monotherapy is safe post LAAO with AMPLATZER™ LAAO

Devices

Aspirin alone for post-implant

antithrombotic therapy

Korsholm K, et al. EuroIntervention. 2016 Dec 15. [Epub ahead of print]

Study and patient characteristics

Enrollment107 patients

March 2010-March 2015

CHA2DS2-VASc4.4±1.6

HASBLED 4.1±1.1

Follow up Median 2.3 years

Indication80% Bleeding indication

Results

Success 100%

Complication

rate

4.6%

Stroke riskAnnual risk of stroke reduced by

61% to predicted rate

Bleeding riskAnnual risk of bleeding reduced by

57%

Device

related

thrombus

2/107 (1.9%)

1 had clopidogrel due to aspirin

intolerance 1 month post implant

1 at 6 weeks managed with heparin

AMPLATZER™ Amulet™ Device

Randomized control trial - ongoing

Study

Overview

Prospective, randomized, multi-center active control trial designed to evaluate the safety and effectiveness of the

AMPLATZER™ Amulet™ Left Atrial Appendage Occluder (LAAO). The AMPLATZER Amulet is intended to reduce the

risk of thromboembolism from the left atrial appendage (LAA) in patients with non-valvular atrial fibrillation (AF).

Objective To evaluate the safety and effectiveness of the AMPLATZER™ Amulet™ device by demonstrating that the device is non-inferior

to the commercially available WATCHMAN™ left atrial appendage closure device (Control) in subjects with non-valvular AF.

Endpoints • Primary safety endpoint:

o Composite of procedure-related complications, all cause death, major bleeding through 12 months

• Primary effectiveness endpoint:

o A composite of ischemic stroke or systemic embolism through 18 months

• Primary mechanism of action endpoint:

o Device closure (defined as residual jet around the device <5mm) at the 45d visit

Design Prospective, global, multi-center active control trial with 1:1 randomization to Amulet™ (Treatment) or WATCHMAN™ (Control),

evaluating approximately >1600 patients

Study

Population

Patients aged 18 and older, with non-valvular atrial fibrillation (AF) who:

• Are at increased risk for stroke and systemic embolism based on CHADS2 and CHADS2-VASc scores

• Are recommended for anticoagulation therapy

• Are deemed by their physician to be suitable for warfarin; and

• Have an appropriate rationale to seek a non-pharmacologic alternative to warfarin

Data

Collection

• Baseline, Procedure, Discharge, Follow-up (45d, 6mo, 12mo, 18mo, 24mo and annually for 5 years)

• Testing/Assessments: TEE (baseline, 45d, 12mo), TTE (at discharge), medication assessment (all visits), MRI/CT (after

suspected stroke/TIA)

Status • Ongoing

• AMPLATZER™ Left Atrial Appendage Occluders demonstrate

experienced operators are able to achieve an implant success rate

between 95% and 100%.

• AMPLATZER™ Left Atrial Appendage Occluders show there is an

overall procedural complication rate of 4% or lower.

• The most common procedure-related safety event is pericardial

effusion, occurring less frequently with increasing operator

experience.

• Closure (<3mm jet at follow up) in more than 90% of patients.

• Longer-term follow-up results show stable and effective LAA

occlusion over time and a reduction in stroke rate between

approximately 60% and 75%, compared to the stroke incidence

predicted by the CHADS2 or CHA2DS2-VASc score.

Summary

• Randomized control trials still lacking

• The majority of patients implanted according to European guidelines

(Unable to tolerate OAC) results demonstrate:

• Percutaneous LAA occlusion is a feasible option for stroke reduction in

AF patients at high risk for stroke who are contraindicated to long term

oral anticoagulation

• Percutaneous LAA occlusion is a feasible option for stroke reduction in

AF patients at high risk for stroke who have suffered a stroke despite OAC.

• LAA occlusion is also associated with markedly less major bleeding than

OAC.

Conclusion

AMPLATZER™ Left Atrial Appendage data...

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