CARDIOLOGY GRAND ROUNDS Title: Reintroduction Overview: Watchman Speaker: Mario Goessl, MD, FACC, FAHA, FESC, FSCAI Minneapolis Heart Institute at Abbott Northwestern Hospital Date: Monday, October 24, 2016 Time: 7:00 8:00 AM Location: ANW Education Building, Watson Room OBJECTIVES At the completion of this activity, the participants should be able to: 1. Define the rationale behind LAA closure. 2. List indications for the Watchman device. 3. Describe the Watchman procedure. ACCREDITATION Physician: This activity has been planned and implemented in accordance with the accreditation requirements and policies of the Accreditation Council for Continuing Medical Education (ACCME) through the joint providership of Allina Health and Minneapolis Heart Institute Foundation. Allina Health is accredited by the ACCME to provide continuing medical education for physicians. Allina Health designates this live activity for a maximum of 1.0 AMA PRA Category 1 Credit(s) TM. Physicians should claim only the credit commensurate with the extent of their participation in the activity. Nurse: This activity has been designed to meet the Minnesota Board of Nursing continuing education requirements for 1.2 hours of credit. However, the nurse is responsible for determining whether this activity meets the requirements for acceptable continuing education. DISCLOSURE STATEMENTS Speaker(s): Dr. Goessl declares that he does not have any conflicts of interest to disclose. Planning Committee: Dr. JoEllyn Carol Moore (Abraham), MD, Dr. Alex Campbell, Dr. Kevin Harris, Rebecca Lindberg, Dr. Michael Miedema, Dr. Scott Sharkey, Eva Zewdie and Jolene Bell Makowesky have declared that they do not have any conflicts of interest associated with the planning of this activity. Dr. David Hurrell declares the following relationship honoraria: Boston Scientific. ACKNOWLEDGMENT OF SUPPORT This presentation is partially funded by an educational grant from Abbott Vascular. PLEASE SAVE A COPY OF THIS FLIER AS YOUR CERTIFICATE OF ATTENDANCE Signature: My signature verifies that I have attended the above stated number of hours of the CME activity. Allina Health - Learning & Development - 2925 Chicago Ave - MR 10701 - Minneapolis MN 55407
(Re) Introduction of the WATCHMAN device for Left atrial appendage closure (LAAC) Mario Gössl, MD, FACC, FAHA, FESC, FSCAI Director, Transcatheter Research and Education & Structural Interventional Cardiology Fellowship Atrial Fibrillation & Stroke Risk AF is the most common cardiac arrhythmia AF increases risk of stroke Blood clots form in the left atrial appendage Many patients are unprotected < Non-LAA 10% 90% Thrombus Originate LAA 10% 15% Intolerant Non-LAA 70% 15% 45% Treated 55% with Untreated Contraindicated Treated Warfarinwith 90% Warfarin Thrombus Originate LAA > 33M people with AF Worldwide 1 5x greater risk of stroke with of stroke-causing clots that come from the left atrium in non-valvular AF are formed in the LAA 3 AF 2 >90% ~45% of patients eligible for warfarin are untreated (tolerance/adherence) 4 1 Chugh, S et al. Circulation, 2014; 129: 837-847 2 Holmes DR, Atrial Fibrillation and Stroke Management: Present and Future, Seminars in Neurology 2010;30:528 536. 3 Blackshear JL. Odell JA., Annals of Thoracic Surgery. 1996;61:755-759 4 Waldo, AL. JACC 2005;46:1729-1736. / Holmes DR et al, Atrial Fibrillation and Stroke Management: Present and Future, Seminars in Neurology 2010;30:528 536 1
2014 ACC/AHA/HRS Treatment Guidelines to Prevent Thromboembolism in Patients with AF Assess stroke risk with CHA 2 DS 2 -VASc score Score 1: Annual stroke risk 1%, oral anticoagulants or aspirin may be considered Score 2: Annual stroke risk 2%-15%, oral anticoagulants are recommended Balance benefit vs. bleeding risk 2014 AHA/ACC/HRS Guideline for the Management of Patients with AF January, CT. et al. 2014 AHA/ACC/HRS Guideline for the Management of Patients With Atrial Fibrillation. JACC. 2014; doi: 10.1016/j.jacc.2014.03.022 Oral Anticoagulation is Standard of Care, but Not Ideal for All Use of OACs in AF Patients peaks at ~50%, use declines with increasing risk Warfarin Bleeding risk Daily regimen High non-adherence rates Regular INR monitoring Food and drug interaction issues Complicates surgical procedures Novel Oral Anticoagulants Bleeding risk Daily regimen High non-adherence rates Complicates surgical procedures Lack of reversal agents High cost 1. Hsu, J et al. JAMA Cardiol. Published online March 16, 2016. doi:10.1001/jamacardio.2015.0374 2
Despite NOAC Adoption and Ability to Switch NOACs, Adherence to Anticoagulation Remains a Challenge ~30% of NOAC patients stop taking any drug at 2 years Source: Martinez C, et al. Therapy Persistence in Newly Diagnosed Non-Valvular Atrial Fibrillation Treated with Warfarin or NOAC. A Cohort Study. Thromb Haemost. 2015 Dec 22;115(1):31-9. doi: 10.1160/TH15-04-0350. WATCHMAN Left Atrial Appendage Closure (LAAC) Device Procedure One-time implant that does not need to be replaced Performed in a cardiac cath lab/ep suite, does not need hybrid OR Performed by a Heart Team IC/EP or IC&EP, TEE, General Anesthesia, Surgical Back- up, WATCHMAN Clinical Specialist Transfemoral Access: Catheter advanced to the LAA via the femoral vein (Does not require open heart surgery) General anesthesia* 1 hour procedure* 1-2 day hospital stay* * Typical to patient treatment in U.S. clinical trials 3
WATCHMAN LAAC Closure Device 160 Micron Membrane Minimally Invasive, Local Solution Available sizes: 21, 24, 27, 30, 33 mm diameter Intra-LAA design Avoids contact with left atrial wall to help prevent complications Nitinol Frame Conforms to unique anatomy of the LAA to reduce embolization risk 10 active fixation anchors - designed to engage tissue for stability Anchors 1. Holmes, DR et al. JACC 2014; Vol. 64, No. 1 Proximal Face Minimizes surface area facing the left atrium to reduce post-implant thrombus formation 160 micron membrane PET cap designed to block emboli and promote healing Warfarin Cessation 92% after 45 days, >99% after 12 months 1 95% implant success rate 1 WATCHMAN Therapy National Coverage Determination Effective Feb. 8, 2016 CMS will cover percutaneous LAAC implants when specific criteria are met: Documented in medical record Eligible patients must have a CHADS 2 score 2 or a CHA 2 DS 2 -VASc score 3 Patients must be suitable for short-term warfarin, but deemed unable to take long-term oral anticoagulation Documented evidence of a formal shared decision interaction between the patient and an independent non-interventional physician using an OAC evidence-based decision tool LAA Registry: Patients must be enrolled in a prospective national registry Operator requirements: IC or EP or cardiovascular surgeon must have performed at least 25 transseptal punctures (TSP) through intact septum Must maintain at least 25 TSP over a two year period (at least 12 are LAAC) Facility Requirements: The procedure must be furnished in a hospital with an established structural heart disease (SHD) and/or electrophysiology (EP) program 4
WATCHMAN Device Patient Selection 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 CHADS 2 or CHA 2 DS 2 -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. SH-230506-AD June15 * Please refer to product DFU for more specific details on patient selection WATCHMAN LAAC Procedure Implant Video 5
Device Release Criteria: PASS WATCHMAN Device features one-step deployment Recapturable and Repositionable All criteria must be met prior to device release (PASS) Position device is distal to or at the ostium of the LAA Anchor fixation anchors engaged / device is stable Size device is compressed 8-20% of original size Seal device spans ostium, all lobes of LAA are covered Caution: Investigational device limited to investigational use only under US federal law. Not for sale. Device Release Criteria Position Device should be at or just distal to the LAA ostium 6
Device Release Criteria Anchor Pass or Fail Test 1. To test stability, gently retract deployment knob and let go, observe device returns to original position Deployment Knob Core Wire Hemostasis Valve 2. If the device moves to where position is no longer acceptable or the compression is no longer sufficient, the device should be recaptured 3. Test stability more than once if device stability is questionable Device Release Criteria - Size Device Compression Table 8 20% of original device size selected 20.8 Device Size (uncompressed diameter) Maximum (20%) Compression Measured Diameter* Minimum (8%) Compression Measured Diameter* 21 16.8 mm 19.3 mm 24 19.2 mm 22.1 mm 27 21.6 mm 24.8 mm 30 24.0 mm 27.6 mm 33 26.4 mm 30.4 mm *Measure in-situ device diameter at approximate TEE angles of 0, 45, 90 and 135 degrees to accurately assess device compression Caution: Investigational device limited to investigational use only under US federal law. Not for sale. 7
Device Release Criteria Seal Residual flow around the device of 5mm acceptable If all 4 device release criteria are met (PASS), device can be released Counter clockwise on proximal handle 3-5 turns WATCHMAN Device Endothelialization Canine Model 30 Day Canine Model 45 Day Human Pathology - 9 Months Post-implant (Non-device related death) Images on file at Boston Scientific Corporation. Results in animal models may not necessarily be indicative of clinical outcomes. 8
Observed Rates of Major Bleeding Over Time According to Treatment Group Post Procedure Therapy Warfarin + ASA (81mg) daily Clopidogrel (75mg) + ASA (325 mg) daily Destination Therapy ASA (325mg) daily Overall Implant 45 days* 6 months Post Procedure Destination *if leak >5mm, patients remained on warfarin + ASA until seal documented, skipping the clopidogrel + ASA pharmacotherapy Bleeding Rate (n events / N at risk) 10.8 (79/732) 5.9 (40/682) 3.2 (19/601) LAAC (n=732) Event Rate per 100 pt-yrs (n events / N at risk) 3.5 (79/2268) 1.8 (40/2255) 1.0 (19/1958 Long-term warfarin (n=382) Bleeding Rate (n events/n at risk) 11.3 (43/382) 11.3 (43/381) 9.7 (35/360) Event Rate per 100 pt-yrs (n events / N at risk) 3.6 (43/1187) 3.6 (43/1180) 3.5 (35/1004) Rate Ratio P value 0.96 0.84 0.49 0.001 0.28 <0.001 Overall period defined as after randomization to the end of follow-up; post-procedural period as >7 days after randomization to the end of follow-up; destination therapy period as beyond 180 days post-randomization, when patients assigned to LAA closure were eligible to receive aspirin alone. Price, M. J., V. Y. Reddy, et al. JACC: CV Interv 2015; 8(15): 1925-1932 PROTECT AF/PREVAIL Pooled Analysis: Less Bleeding with WATCHMAN TM Device 6 Months Post-Implant 100 90 Free of Major Bleeding Event (%) 80 70 60 WATCHMAN Warfarin HR = 0.29 p<0.001 71% Relative Reduction In Major Bleeding after cessation of anti-thrombotics WATCHMAN Device Arm Drug Protocol 50 Warfarin +Aspirin Warfarin +Aspirin Aspirin+ Clopidogrel Aspirin 0 7 8 45 46 180 6 60 Time (days) Time (months) Definition of bleeding: Serious bleeding event that required intervention or hospitalization according to adjudication committee Price, MJ. Avoidance of Major Bleeding with WATCHMAN Left Atrial Appendage Closure Compared with Long-Term Oral Anticoagulation : Pooled Analysis of the PROTECT-AF and PREVAIL RCTs. TCT 2014 (abstract) SH-230506-AD June15 9
Implant Success & Warfarin Cessation Implant success defined as deployment and release of the device into the left atrial appendage p = 0.04 Warfarin Cessation Study 45-day 12-month PROTECT AF 87% >93% CAP 96% >96% PREVAIL 92% >99% PROTECT AF and CAP: Reddy, VY et al. Circulation. 2011;123:417-424. PREVAIL: Holmes, DR et al. JACC 2014; 64(1):1-12. PREVAIL Implant Success No difference between new and experienced operators Experienced Operators n=26 96% New Operators n=24 93% p = 0.28 Favorable Procedural Safety Profile: 7-Day Safety Events 12.0% 10.0% 9.9% Patients with Safety Event (%) 8.0% 6.0% 4.0% Learning Curve 4.8% 4.1% 4.1% 3.8% 2.0% 0.0% PROTECT AF CAP PREVAIL CAP2 n=232 n=231 n=566 n=269 n=579 1 st Half 2 nd Half All Device and/or procedure-related serious adverse events within 7 Days Source: FDA Oct 2014 Panel Sponsor Presentation. ~50% New Operators in PREVAIL 10
PROTECT AF 4-Year Results in JAMA WATCHMAN TM Met Criteria for both Noninferiority and Superiority for the Primary Composite Endpoint Compared to Warfarin Reddy, VY et al. JAMA. 2014;312(19):1988-1998. SH-230506-AD June15 PROTECT AF: Final, 5-Year Primary Efficacy Events Consistent with 4-Year Results Event Rate (per 100 Pt-Yrs) Rate Ratio Posterior Probability WATCHMAN Warfarin (95% CrI) Non-inferiority Superiority Primary efficacy 2.2 3.7 0.61 (0.42, 1.07) >99.9% 95.4% Stroke (all) 1.5 2.2 0.68 (0.42, 1.37) 99.9% 83% Systemic embolism 0.2 0.0 N/A -- -- Death (CV/unexplained) 1.0 2.3 0.44 (0.26, 0.90) >99.9% 98.9% Source: FDA Oct 2014 Panel Sponsor Presentation. SH-230506-AD June15 11
Meta-Analysis Shows Comparable Primary Efficacy Results to Warfarin HR p-value Efficacy 0.79 0.22 All stroke or SE 1.02 0.94 Ischemic stroke or SE 1.95 0.05 Hemorrhagic stroke 0.22 0.004 Ischemic stroke or SE >7 days 1.56 0.21 CV/unexplained death 0.48 0.006 All-cause death 0.73 0.07 Major bleed, all 1.00 0.98 Major bleeding, non procedure-related 0.51 0.002 Favors WATCHMAN Favors warfarin 0.01 0.1 1 10 Hazard Ratio (95% CI) Source: Holmes DR, et al. Holmes, DR et al. JACC 2015; In Press. Combined data set of all PROTECT AF and PREVAIL WATCHMAN patients versus chronic warfarin patients SH-230506-AD June15 WATCHMAN TM Device Reduced Ischemic Stroke Over No Therapy 8 7 Ischemic Stroke Risk (Events/100 Patient-Years) 6 5 4 3 2 1 0 79% Relative Reduction PROTECT AF 67% Relative Reduction PREVAIL Only CAP 83% Relative Reduction Imputed Ischemic Stroke Rate* Observed WATCHMAN Ischemic Stroke Rate Baseline CHA 2DS 2-VASc = 3.4 Baseline CHA 2DS 2-VASc = 3.8 Baseline CHA 2DS 2-VASc = 3.9 * Imputation based on published rate with adjustment for CHA 2 DS 2 -VASc score (3.0); Olesen JB. Thromb Haemost (2011) FDA Oct 2014 Panel Sponsor Presentation. Hanzel G, et al. TCT 2014 (abstract) SH-230506-AD June15 12
ASAP-TOO Randomized, controlled IDE study in subjects unsuitable for oral anticoagulation - Primary Endpoint: ischemic stroke/systemic embolism - Estimated Enrollment: ~900 randomized subjects - Study Start Date: FPI 2 nd half 2016 - Target Follow-up Duration: 5-year follow up - Sites: ~100 sites globally - Arms: WATCHMAN medication: 3-months DAPT, followed by 9-months low dose ASA Control group: Single antiplatelet or no therapy Randomization: 2:1 Questions THANK YOU! 13