Download WATCHMANTM Left Atrial Appendage Closure (LAAC

Kenneth Stein, MD FACC FHRS
Senior Vice President and Chief Medical Officer,
Rhythm Management and Global Health Policy
Boston Scientific
SH-450507-AA FEB2017
Lessons From WATCHMAN
Launch: FDA, CMS, and the
Launch of a New Therapy
Disclosure
This presentation may include products and/or
uses that have not been approved or cleared by
the U.S. Food and Drug Administration and are
not available for sale in the U.S.
All future product approval and launch dates are
based on estimates of completion of regulatory
submissions, review and/or approval or clearance,
as well as other business considerations.
Dr. Stein is a Boston Scientific employee and
shareholder.
2
Procedural Success1-2
~50%
new operators
100.0%
90.9%
~70%
new operators
98.5%
94.4%
95.1%
94.8%
CAP1
N=566
PREVAIL
N=265
CAP2
N=579
95.6%
90.0%
80.0%
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70.0%
60.0%
50.0%
40.0%
30.0%
20.0%
10.0%
0.0%
PAF
N=449
EWOLUTION
N=1019
Implant success defined as deployment and release of the device into the LAA; no leak ≥ 5 mm
1 WATCHMAN FDA Panel Sponsor Presentation. Oct 2014; 2 Boersma, L.et al. EHJ; published online Jan 2016 in press; 3
Post-FDA
Approval
N=3822
Outcomes in the Post-FDA Approval
Watchman Experience
Pericardial Tamponade
Post-FDA Approval Experience
39 (1.02%)
Treated with Pericardiocentesis
24 (0.63%)
Treated Surgically
12 (0.31%)
Resulted in Death
Pericardial Effusion – No Intervention
3 (0.078%)
11 (0.29%)
Procedure-Related Stroke
Device Embolization
3 (0.078%)
9 (0.24%)
Removed Percutaneously
3
Removed Surgically
6
Death
Procedure-Related Mortality
3 (0.078%)
Additional Mortality within 7 days
1 (0.026%)
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Complications
Comparison of Procedural Complications
Across Watchman Studies
AGGREGATE
CLINICAL DATA
Clinical Trial
Experience
5.0%
PROCEDURAL PARAMETERS
6720
Pericardial Tamponade
Implantation Success, %
94.9%
COMPLICATION RATES
Pericardial Tamponade
1.28%
Procedure-Related Stroke
0.18%
Device Embolization
0.25%
Procedure-Related Death
0.06%
Complication Rates
4.0%
Procedure-Related Stroke
Device Embolization
3.0%
2.0%
1.0%
0.0%
Procedure-Related Death
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No. of Procedures
Post Approval
Experience
WATCHMAN ‘NESTed’ Post Approval
Study
• 2000 patients from the NCDR LAAO Registry
– This study is ‘nested’ within the larger LAAO Registry. The data collected within this study will be
collected as part of the LAAO registry. Thus, no additional data elements are required as part of
the WATCHMAN NESTed study
• Follow-up occurring at implant, 45 days, 6, 12 and 24 months
• 1st Primary Effectiveness Endpoint*
– The occurrence of stroke (including ischemic and/or hemorrhagic), cardiovascular death
(cardiovascular and/or unexplained cause) and systemic embolism at 24 months.
• 2nd Primary Effectiveness Endpoint*
– The occurrence (excluding the first 7 days post implant) of ischemic stroke or systemic embolism
(thrombolic events) at 24 months.
• Primary Safety Endpoint*
– The occurrence of major safety events between the time of implant and within 7 days of the
procedure or by hospital discharge, whichever is later
• First data analysis expected Q1 2017
*Results will be compared to Performance Goals based on historical data
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– CMS linkage to NESTed study patients for follow-up data collection during years 2-5
ASAP-TOO
Assessment of the WATCHMAN Device in Patients
Unsuitable for Oral Anticoagulation
• 888 subjects at 100 global sites (65 US, 35 Intl)
• Randomized 2 Device to 1 Control
– Control group: Single antiplatelet or no therapy
– Device group: WATCHMAN plus 3-months DAPT, followed
by 9-months low dose ASA
• Primary effectiveness endpoint: ischemic stroke/systemic
embolism
• 5-year follow up
• PIs: Vivek Reddy, Maurice Buchbinder, Jacqueline Saw
• Current status: currently enrolling
Clinicaltrials.gov Identifier: NCT02928497
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Indication expansion IDE study testing the safety and
effectiveness of WATCHMAN in subjects unsuitable for
oral anticoagulation
The WIN-Her™ Initiative
Program Summary
Patient & physician materials
WIN-Her Initiative Pilot success
 35 - 40% female enrollment
WIN-Her Initiative Data
 future protocol design
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 barriers to female enrollment
LEIO-AF Pre-Clinical
Objective:
• Evaluate safety and feasibility
of LAAC after electrical isolation
in canine model
• 9 canine underwent PVI and LAA electrical isolation and LAAC with
WATCHMAN
Results:
• All PVs and 8/9 LAAs electrically isolated
• Acute LAA reconnection in 4 of 8 LAAs
• 45-Days 7of 8 had persistent LAA electrical isolation
Heart Rhythm. 2015 Jan;12(1):202-10.
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Methods:
LEIO-AF Human Feasibility
48 Screened
25 Excluded Pre-Enrollment
• 23 didn’t meet eligibility criteria
• 2 declined participation
22 catheter ablation + LAAC
• 20/22 successful LAA
isolation
• 20/20* successful LAAC
1 Excluded Post-Enrollment
• LAA ostium >33mm on baseline
CT
2 excluded as unable to achieve
pre-specified LAA electrical
isolation
Follow-up analyzed (n=20)
*2 unsuccessful LAA electrical isolation therefore LAAC not attempted
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23 Enrolled
LEIO-AF Human Feasibility:
Kaplan Meier
1.0
0.6
Treated
Blanking period
Control
0.4
0.2
0.0
0
60
120
180
240
Follow up (days)
300
360
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AF/AT-free survival
0.8
LEIO:AF
Study Assumptions
• 10 Investigational Sites
– Located in the ~3 countries in EU
– Have a RhythmiaTM System
• Utilize WATCHMANTM FLX* Device
• Randomization:
– Control Group: Conventional Persistent AF Ablation
– Treatment Group: Conventional Persistent AF, LAA Electrical
Isolation, WATCHMAN Implant
• Visits at Baseline, 6-wk, 3-, 6-, 12- and 24-months
• Primary Endpoint Evaluation at 12-months
*Caution: Investigational Device. Limited by Federal (or US) law to investigational use only. Not available for sale.
CE Mark pending – not available for sale in the European Economic Area (EEA).
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• Sample Size: ~ 214 subjects
LEIO-AF:
Endpoints
Primary Safety
Secondary
• Freedom from AF/AT at 12 months
• Major procedure/device events
• Stroke, Major bleeding, Death
•
•
•
•
Freedom from AF at 12 months
Change in AF burden
Serious adverse cardiovascular event
Change in AF symptom score (AF-EQT and EQ-5D health
score)
• Cost effectiveness
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Primary Efficacy
INDICATIONS FOR USE
The WATCHMAN Device is indicated to reduce the risk of thromboembolism from the left atrial appendage in patients with non-valvular atrial fibrillation who:
• Are at increased risk for stroke and systemic embolism based on CHADS2 or CHA2DS2-VASc scores and are recommended for anticoagulation therapy;
• Are deemed by their physicians to be suitable for warfarin; and
• Have an appropriate rationale to seek a non-pharmacologic alternative to warfarin, taking into account the safety and effectiveness of the device compared to warfarin.
The WATCHMAN Access System is intended to provide vascular and transseptal access for all WATCHMAN Left Atrial Appendage Closure Devices with Delivery Systems.
CONTRAINDICATIONS
Do not use the WATCHMAN Device if:
• Intracardiac thrombus is visualized by echocardiographic imaging.
• An atrial septal defect repair or closure device or a patent foramen ovale repair or closure device is present.
• The LAA anatomy will not accommodate a device. See Table 46 in the DFU.
• Any of the customary contraindications for other percutaneous catheterization procedures (e.g., patient size too small to accommodate TEE probe or required catheters) or conditions (e.g., active infection, bleeding disorder) are present.
• There are contraindications to the use of warfarin, aspirin, or clopidogrel.
• The patient has a known hypersensitivity to any portion of the device material or the individual components (see Device Description section) such that the use of the WATCHMAN Device is contraindicated.
WARNINGS
• Device selection should be based on accurate LAA measurements obtained using fluoro and ultrasound guidance (TEE recommended) in multiple angles (e.g., 0º, 45º, 90º, 135º).
• Do not release the WATCHMAN Device from the core wire if the device does not meet all release criteria.
• If thrombus is observed on the device, warfarin therapy is recommended until resolution of thrombus is demonstrated by TEE.
• The potential for device embolization exists with cardioversion <30 days following device implantation. Verify device position post-cardioversion during this period.
• Administer appropriate endocarditis prophylaxis for 6 months following device implantation. The decision to continue endocarditis prophylaxis beyond 6 months is at physician discretion.
• For single use only. Do not reuse, reprocess, or resterilize.
PRECAUTIONS
• The safety and effectiveness (and benefit-risk profile) of the WATCHMAN Device has not been established in patients for whom long-term anticoagulation is determined to be contraindicated.
• The LAA is a thin-walled structure. Use caution when accessing the LAA and deploying the device.
• Use caution when introducing the WATCHMAN Access System to prevent damage to cardiac structures.
• Use caution when introducing the Delivery System to prevent damage to cardiac structures.
• To prevent damage to the Delivery Catheter or device, do not allow the WATCHMAN Device to protrude beyond the distal tip of the Delivery Catheter when inserting the Delivery System into the Access Sheath.
• If using a power injector, the maximum pressure should not exceed 100 psi.
• In view of the concerns that were raised by the RE-ALIGN1 study of dabigatran in the presence of prosthetic mechanical heart valves, caution should be used when prescribing oral anticoagulants other than warfarin in patients treated with the
WATCHMAN Device. The WATCHMAN Device has only been evaluated with the use of warfarin post-device implantation.
ADVERSE EVENTS
Potential adverse events (in alphabetical order) which may be associated with the use of a left atrial appendage closure devi ce or implantation procedure include but are not limited to:
Air embolism, Airway trauma, Allergic reaction to contrast media/medications or device materials, Altered mental status, Anemia requiring transfusion, Anesthesia risks, Angina, Anoxic encephalopathy, Arrhythmias, Atrial septal defect , AV fistula ,
Bruising, hematoma or seroma, Cardiac perforation , Chest pain/discomfort, Confusion post procedure, Congestive heart failure, Contrast related nephropathy, Cranial bleed, Decreased hemoglobin, Deep vein thrombosis, Death, Device embolism,
Device fracture, Device thrombosis, Edema, Excessive bleeding, Fever, Groin pain, Groin puncture bleed, Hematuria, Hemoptysis, Hypotension, Hypoxia, Improper wound healing, Inability to reposition, recapture, or retrieve the device, Infection /
pneumonia, Interatrial septum thrombus, Intratracheal bleeding, Major bleeding requiring transfusion, Misplacement of the device / improper seal of the appendage / movement of device from appendage wall, Myocardia erosion, Nausea, Oral
bleeding, Pericardial effusion / tamponade, Pleural effusion, Prolonged bleeding from a laceration, Pseudoaneurysm, Pulmonary edema, Renal failure, Respiratory insufficiency / failure, Surgical removal of the device, Stroke – Ischemic , Stroke –
Hemorrhagic, Systemic embolism, TEE complications (throat pain, bleeding, esophageal trauma), Thrombocytopenia, Thrombosis, Transient ischemic attack (TIA), Valvular damage, Vasovagal reactions
There may be other potential adverse events that are unforeseen at this time.
CAUTION: Federal law (USA) restricts this device to sale by or on the order of a physician. Rx only. Prior to use, please see the complete “Directions for Use” for more information on Indications, Contraindications, Warnings, Precautions, Adverse
Events, and Operator’s Instructions.
© 2015 Boston Scientific Corporation or its affiliates. All rights reserved.
1Eikelboom JW, Connolly SJ, Brueckmann M, et al. N Engl J Med 2013;369:1206-14.
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ABBREVIATED STATEMENT (US)
WATCHMANTM Left Atrial Appendage Closure Device
with Delivery System and WATCHMAN Access System