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Left Atrial Appendage Closure: Prevention of Thromboembolism in Atrial Fibrillation Thank you for inviting me here – it’s a real pleasure to be able to.

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Presentation on theme: "Left Atrial Appendage Closure: Prevention of Thromboembolism in Atrial Fibrillation Thank you for inviting me here – it’s a real pleasure to be able to."— Presentation transcript:

1 Left Atrial Appendage Closure: Prevention of Thromboembolism in Atrial Fibrillation
Thank you for inviting me here – it’s a real pleasure to be able to be with you this evening. I’ve been the chief medical officer for CRM and EP for over a year now and I thought that this would be a great opportunity to reflect back on what I’ve learned in my time here and to share with you my thoughts on what practicing EPs need from you and from BSC. [CLICK] Maurice Buchbinder, MD, FACC, FSCAI Director, Foundation for Cardiovascular Medicine, San Diego, CA Director, Advanced Interventional Therapies, Gagnon Cardiovascular Institute, Morristown, NJ

2 Maurice Buchbinder, MD Advisory Committee Abbott Laboratories
Boston Scientific Corporation Ownership Interest (Stocks, Stock Options, or other Ownership Interest): Cordis Corporation EndoCross

3 Intellectual Property
MiCardia Board Membership

4 Atrial Fibrillation and Stroke
Atrial Fibrillation is one of the MOST common cardiac Dysrrhythmias seen in clinical practice 1,2 Untreated, it is associated with nearly FIVEFOLD increase in stroke rates Strokes are often more severe in patients with AF Paroxysmal AF and persistent AF are associated with the same incremental risk of cerebrovascular events 1Go, et al. Prevalence of Diagnosed Atrial Fibrillation in Adults. JAMA. 2001; 285: 2ACC/AHA/ESC Guidelines for the management of patients with atrial fibrillation. JACC. 2001; 38:1. 3Wolf, Abbott, Kannel. Atrial fibrillation as an independent risk factor for stroke: the Framingham Study. Stroke, 1991; 5

5 CHADS2 Score and Stroke Rate
Annual Risk of Stroke Adapted from Gage et al, JAMA 2001;285:2864–2870

6 Camm et al, European Heart Journal doi:10.1093/eurheartj/ehq278
CHA2DS2-VASc 2010 ESC AF Guidelines now call for use of CHA2DS2-VASc score Recommend oral anticoagulation for score 2 or greater and either anticoagulation or aspirin for score =1 Camm et al, European Heart Journal doi: /eurheartj/ehq278

7 Inadequate VKA Treatment for AF
Adequacy of Anticoagulation in Patients with AF in Primary Care Practice INR above target 6% INR in target range 15% No warfarin 65% Sub-therapeutic INR 13% Samsa GP, et al. Arch Intern Med 2000;160:967. 8

8 Anticoagulation and Bleeding
“An assessment of bleeding risk should be part of the patient assessment before starting anticoagulation ... It would seem reasonable to use the HAS-BLED score to assess bleeding risk in AF patients, whereby a score of ≥3 indicates ‘high risk’, and some caution and regular review of the patient is needed following the initiation of antithrombotic therapy,whether with VKA or aspirin.” According to HAS-BLED, 61% of pts currently on warfarin for AF are at “moderate” risk of bleeding and additional 19% are at “high” risk! Camm et al, European Heart Journal doi: /eurheartj/ehq278 Pisters R, et al Chest 2010; 138:

9 New Anticoagulants for AF: Potential Changes in Recommendations
Medication Action Phase III Trial Comparator Design n Dabigatran DTI RE-LY Warfarin Non-inferiority 18 113 Apixaban Anti Xa AVERROES Aspirin Superiority 5 599 ARISTOLE 18 201 Rivaroxaban ROCKET AF 14 269 Edoxaban ENGAGE 21 500 Biotinylated Idraparinux BOREALIS-AF 9 600 Tecarfarin VKA EmbraceAC 612 Others include: betrixaban (EXPLORE-Xa), darexaban (OPAL-1), AZD0837 10

10 Stroke Prevention: Anticoagulant Effect
Meta-analysis of ischemic stroke or systemic embolism Favors warfarin 0.3 0.6 0.9 1.2 1.5 Favors other Rx W vs Placebo W vs Wlow dose W vs Aspirin W vs Aspirin + Clop W vs Ximelagatran W vs Dabigatran 110 W vs Rivaroxaban W vs Dabigatran 150 Category 1.8 2.0 Modified from Camm AJ. EHJ 2009;30:2554-5 12 8 9 11

11 Bleeding Risks with Old and New Drugs
P=.31 P=.003 Bleeding Risk % per year Connolly SJ, et.al., N Engl J Med Sep 17;361(12):

12 Thromboembolism versus Haemorrhage
Bleeding risk ? Left Atrial Occlusion Device 3-4% pa Thromboembolic risk 1-2% pa 13

13 WATCHMAN® LAA Closure: Rationale and Technique
14

14 LAA Thrombus

15 Location of Thombi in Left Atrium
Location Frequency (%) 91% in LAA Blackshear J.L. Odell J.A., Annals of Thoracic Surgery, 1996;61:

16 WATCHMAN® LAA Closure System Implanted Device
Frame: Nitinol structure Available sizes: 21, 24, 27, 30 & 33mm (diameter) 10 Fixation anchors around device perimeter engage LAA tissue Contour shape accommodates most LAA anatomy Fabric Cap: (PET) Fabric Polyethyl terephthalate prevents harmful emboli from exiting during the healing process 160 micron filter PET fabric Anchors

17 WATCHMAN® LAA Closure System WATCHMAN Access System
Transseptal Access System Double or Single Curve styles 14F O.D. (4.7 mm), 12F I.D cm working length Double Curve Single Curve Preformed curve shapes guide position in LAA

18 OPTIMAL POSITION

19 WATCHMAN® LAA Closure: Clinical Program
20

20 Continued Access Registry (CAP)
Clinical Studies STUDY PATIENTS SITES COMMENTS Pilot 66 8 318 patient years of follow-up 30 patients with 5+ years of follow-up PROTECT AF 800 59 1,500 patient years of follow-up 27 months average follow-up per patient Continued Access Registry (CAP) 566 26 Significantly improved safety results ASAP 135 4 Treat patients contra-indicated for warfarin EVOLVE 69 3 Evaluate next generation WATCHMAN® PREVAIL 253 ≤50 Same endpoints as PROTECT AF Revised inclusion/exclusion criteria Initiate enrollment October 2010 Total 1,889 21

21 PROTECT AF Clinical Trial
Prospective, randomized study of WATCHMAN® LAA Device vs. Long-term warfarin Therapy 2:1 allocation ratio device to control 800 patients enrolled from February 2005 to June 2008 93 roll-in; 707 randomized 59 enrolling centers (U.S. & Europe) Follow-up requirements TEE follow-up at 45 days, 6 months and 1 year Clinical follow-up biannually up to 5 years INR monitoring every 2 weeks for 6 months and monthly thereafter Holmes D R et. Al, Lancet 2009;374:534-42 22 22

22 Holmes D R et. Al, Lancet 2009;374:534-42
Patient Risk Factors Baseline Risk Factors WATCHMAN® N= 463 Control N= 244 P-value CHADS2 Score: 1 2 3 4 5 6 157/463 158/463 88/463 37/463 19/463 4/463 33.9% 34.1% 19.0% 8.0% 4.1% 0.9% 66/244 88/244 51/244 24/244 10/244 5/244 27.0% 36.1% 20.9% 9.8% 2.0% 0.39 AF Pattern: Paroxysmal Persistent Permanent Unknown 200/463 97/463 160/463 6/463 43.2% 21.0% 34.6% 1.3% 99/244 50/244 93/244 2/244 40.6% 20.5% 38.1% 0.8% 0.76 LVEF (%) 57.3 ± 9.7 460 30.0, 82.0 56.7 ± 10.1 239 30.0, 86.0 0.42 23 Holmes D R et. Al, Lancet 2009;374:534-42 23

23 Intent-to-Treat: Primary Efficacy Results
Primary composite efficacy: - stroke (ischaemic or haemorrhagic) death (cardiovascular or unexplained) - systemic embolism Cohort WATCHMAN® Control Relative Risk (95% CI) Posterior Probabilities Rate (95% CI) Non-inferiority Superiority 600 pt-yrs 4.4 (2.6, 6.7) 5.8 (3.0, 9.1) 0.76 (0.39, 1.67) 0.992 0.734 900 pt-yrs 3.4 (2.1, 5.2) 5.0 (2.8, 7.6) 0.68 (0.37, 1.41) 0.998 0.837 1065 pt-yrs* 3.0 (1.9, 4.5) 4.9 (2.8, 7.1) 0.62 (0.35, 1.25) >0.999 0.900 1350 pt-yrs 2.9 (2.0, 4.3) 4.2 (2.5, 6.0) 0.69 (0.42, 1.37) 0.830 1500 pt-yrs (2.1,4.3) 4.3 (2.6, 5.9) 0.71 (0.44, 1.30) 0.846 Results are consistent over time, demonstrating approximately a 30% reduction in primary efficacy, stroke and mortality risk Presented by Holmes, MD, TCT 2010 *Published Results: Holmes D R et. Al, Lancet 2009;374:534-42 24

24 Intent-to-Treat: All Cause Mortality
Cohort WATCHMAN® Control Relative Risk (95% CI) Posterior Probabilities* Rate (95% CI) Non-Inferiority Superiority 600 pt-yrs 3.4 (1.8, 5.4) 4.9 (2.3, 7.8) 0.69 (0.33, 1.66) 0.991 0.779 900 pt-yrs 2.9 (1.7, 4.4) 4.7 (2.5, 7.1) 0.61 (0.32, 1.32) 0.999 0.889 1065 pt-yrs* 3.0 (1.9, 4.5) 4.8 (2.8, 7.1) 0.62 (0.34, 1.24) >0.999 0.907 1350 pt-yrs 3.1 (2.1, 4.4) 4.4 (2.6, 6.1) 0.70 (0.43, 1.36) 0.823 1500 pt-yrs 3.2 (2.3, 4.5) 4.5 (2.8, 6.2) 0.71 (0.46, 1.28) 0.852 *No adjustment made for multiple comparisons 29% lower relative risk in WATCHMAN® Group Presented by Holmes, MD, TCT 2010 *Published Results: Holmes D R et. Al, Lancet 2009;374:534-42 25

25 PROTECT AF Primary Safety Endpoint*
Peri-procedural events On going bleeding events *Major bleeding and events considered life threatening as defined by CEC David R Holmes, Lancet Vol 374 August 15, 2009 CRV AA-Oct2011

26 Reddy VY et al, Circulation AHA 2011
CAP Results versus Early and Late PROTECT AF: Progression of Procedural Success and Safety Procedure Metrics Pimplant success = 0.001* Pproc. time<0.001* n=271 n=460 Procedure Outcomes P=0.006* P=0.018* P=0.039* *From tests for differences across three groups (early PROTECT AF, late PROTECT AF, and CAP) 27 Reddy VY et al, Circulation AHA 2011 27

27 PREVAIL Study Overview
Scope and Duration: Currently Enrolling Up to 50 U.S. Centers Up to 475 patients (75 roll-in, 400 randomized) 25% randomized patients must be enrolled by new operators Key entry criteria Calculated CHADS2 score of 2 or greater. Patients with a CHADS2 score of 1 may be included if any of the following apply: Female age 75 or older Baseline LVEF ≥ 30 and < 35% Aged and has diabetes or coronary artery disease Aged 65 or greater and has congestive heart failure 28

28 LAA Occlusion – The Future
ASAP Trial – 127 Patients enrolled Use in patients contraindicated to oral anticoagulation, even for short periods EVOLVE Trial – Enrollment complete in EU Next Generation Watchman Device 29

29 Conclusions Thromboembolism is AF is a major cause of morbidity and mortality although Oral Anticoagulation is Effective, many patients will not tolerate it due to ONGOING risk of major bleeding WATCHMAN® LAA Closure Device obliterates the Left Atrial Appendage preventing emboli from forming in LAA In Protect-AF (800 patients, 1500 patient-years of follow-up), the device was non-inferior to oral anticoagulation in patients at high-risk of thrombo embolism with a trend toward improved outcomes The PREVAIL, ASAP and EVOLVE trials will provide further information on the safety and effectiveness of the present device in the indicated population as well as in the next generation technology.


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