Left Atrial Appendage Occlusion

Transcription

1 Left Atrial Appendage Occlusion A new strategy to prevent stroke in atrial fibrillation Ashok Talreja MD and Arijit Chanda MD VHVI symposium 24th February 2018

2 Outline of presentation 1. Risk of stroke in AF patients 2. Bleeding risk 3. Clinical evidence for LAAO occlusion 4. Long term safety and efficacy data 5. Patient selection and preparation 6. Implant procedure 7. Followup Dr. Talreja Dr. Chanda

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5 CHA 2 DS 2 -VASc Risk factor score C Congestive heart failure/lv dysfunction 1 H Hypertension 1 A 2 Age 75y 2 D Diabetes mellitus 1 S 2 Stroke/TIA/TE 2 V Vascular disease (prior myocardial infarction, peripheral artery disease, or aortic plaque) 1 A Age 65-74y 1 Sc Sex category (ie female gender) 1 Maximum Score 9 maximum score is 9 since age may contrubute 0, 1, or 2 points Lip GY, et al., Chest 137, , 2010

6 CHA 2 DS 2 -VASc overall event rates %/year 6 Stroke and systemic embolism CHA 2 DS 2 - VASc No of patients

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10 Relation of HAS-BLED score to bleeding risk

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12 Oral Anticoagulation is Standard of Care, but Not Ideal for All AF Patients Using Anticoagulation 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 Anticoagulation Use Declines with Increased Stroke Risk 1 CHADS 2 Score p < (n=27,164) 1. Piccini, et al.. Pharmacotherapy in Medicare beneficiaries with atrial fibrillation. Heart Rhythm. 2012;9: SH AC JUN 2015

13 Anticoagulant Therapy Carries Risk of Intracerebral Hemorrhage or Death Spontaneous intraparenchymal bleed Hemorrhagic transformation SH AC JUN 2015

14 Despite Increasing NOAC Adoption, Overall Rate of Anticoagulation in High Risk NVAF Patients has Not Improved Anticoagulant Use in Patients with NVAF and CHADS 2 2 Total on Oral Anticoagulation Warfarin NOACs n=25719 n=29194 n=31582 n=36490 n=67102 n=70667 n=70320 n=71396 Results from the NCDR PINNACLE Registry 1 1. Jani, et al. Uptake of Novel Oral Anticoagulants in Patients with Non-Valvular and Valvular Atrial Fibrillation: Results from the NCDR-Pinnacle Registry. ACC 2014 SH AC JUN 2015

15 Discontinuation and Major Bleeding Rates with NOACs Treatment Study Drug Discontinuation Rate Major Bleeding (rate/year) Rivaroxaban 1 24% 3.6% Apixaban 2 25% 2.1% Dabigatran 3 (150 mg) Edoxaban 4 (60 mg / 30 mg) 21% 3.3% 33 % / 34% 2.8% / 1.6% Warfarin % % There is an unmet need of stroke risk reduction for patients with AF who are seeking an alternative to long-term OACs 1 Connolly, S. NEJM 2009; 361: yrs follow-up (Corrected) 2 Patel, M. NEJM 2011; 365: yrs follow-up, ITT 3 Granger, C NEJM 2011; 365: yrs follow-up, 4 SH AC JUN 2015

16 Connection Between Non-Valvular AF-Related Stroke and the Left Atrial Appendage AF Creates Environment for Thrombus Formation in Left Atrium Stasis-related LA thrombus is a predictor of TIA 1 and ischemic stroke 2. In non-valvular AF, >90% of stroke-causing clots that come from the left atrium are formed in the LAA Stoddard et al. Am Heart J. (2003) 2. Goldman et al. J Am Soc Echocardiogr (1999) 3 Blackshear JL. Odell JA., Annals of Thoracic Surg (1996) SH AC JUN 2015

17 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 SH AG NOV2016

18 * Typical to patient treatment in U.S. clinical trials SH AG NOV2016 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 General anesthesia* (Does not require open heart surgery) 1 hour procedure* 1-2 day hospital stay*

19 WATCHMAN Device Endothelialization Canine Model 30 Day Canine Model 45 Day Images on file at Boston Scientific Corporation. Results in animal models may not necessarily be indicative of clinical outcomes. Human Pathology - 9 Months Post-implant (Non-device related death) SH AG NOV2016

20 Evidence base for Watchman LAAO PROTECT AF CAP Registry PREVAIL CAP2 Registry Totals Enrollment Enrolled Randomized WATCHMAN: warfarin (2:1) Mean Follow-up (years) 463 : : : N/A Patient-years Source: FDA Oct 2014 Panel Sponsor Presentation. SH AG NOV2016

21 Patient Risk Factors Across Trials Characteristic PROTECT AF N=707 CAP N=566 PREVAIL N=407 CAP2 N=579 p-value CHADS 2 Score 2.2 ± ± ± ± 1.1 < CHADS 2 Risk Factors (% of Patients) CHF Hypertension Age <0.001 Diabetes Stroke/TIA < CHA 2 DS 2 -VASc 3.5 ± ± ± ± 1.3 < Source: FDA Oct 2014 Panel Sponsor Presentation. SH AG NOV2016

22 Procedural Success ~50% new operators ~70% new operators Implant success defined as deployment and release of the device into the LAA; no leak 5 mm * The EWOLUTION Registry is a European prospective registry which reflects CE Mark indications for use which differ from the FDA indications for use. SH AG NOV2016

23 Favorable Procedural Safety Profile: All Device and/or Procedure-related Serious Adverse Events within 7 Days ~50% New Operators in PREVAIL N=232 N=231 N=566 N=269 N=579 N= * The EWOLUTION Registry is a European prospective registry which reflects CE Mark indications for use which differ from the FDA indications for use. SH AG NOV2016

24 Favorable Procedural Safety Profile: Major Procedural Complications Across WATCHMAN Studies Clinical Trial Experience Post Approval Experience * The EWOLUTION Registry is a European prospective registry which reflects CE Mark indications for use which differ from the FDA indications for use. SH AG NOV2016

25 Favorable Procedural Safety Profile: Major Procedural Complications Across WATCHMAN Studies PROTECT-AF PREVAIL CAP CAP2 EWOLUTION Post-FDA Approval Aggregate Data Pericardial Tamponade 20 (4.3%) 5 (1.9%) 8 (1.4%) 11 (1.9%) 3 (0.29%) 39 (1.02%) 86 (1.28%) Treated with pericardiocentesis 13 (2.8%) 4 (1.5%) 7 (1.2%) n/a 2 (0.20%) 24 (0.63%) Treated surgically 7 (1.5%) 1 (0.4%) 1 (0.2%) n/a 1 (0.10%) 12 (0.31%) Resulted in death (0.78%) Pericardial effusion no intervention 4 (0.9%) 0 5 (0.9%) 3 (0.5%) 4 (0.39%) 11 (0.29%) 27 (0.40%) Procedure-related stroke 5 (1.15%) 1 (0.37%) 0 2 (0.35%) 1 (0.10%) 3 (0.078%) 12 (0.18%) Device embolization 3 (0.6%) 2 (0.7%) 1 (0.2%) 0 2 (0.20%) 9 (0.24%) 17 (0.25%) Removed percutaneously Removed surgically Death Procedure-related mortality Additional mortality within 7 days (0.1%) 3 (0.078%) 4 (0.06%) (0.17%) 3 (0.29%) 1 (0.026%) 5 (0.07%) * The EWOLUTION Registry is a European prospective registry which reflects CE Mark indications for use which differ from the FDA indications for use. SH AG NOV2016

26 Meta-Analysis Shows Comparable Primary Efficacy Results to Warfarin PROTECT AF 4 Yrs/PREVAIL 2 Yrs HR p-value Efficacy All stroke or SE Ischemic stroke or SE Hemorrhagic stroke Ischemic stroke or SE >7 days CV/unexplained death All-cause death Major bleed, all Major bleeding, non procedure-related Favors WATCHMAN Favors warfarin Hazard Ratio (95% CI) Source: Holmes, J. D. R., S. K. Doshi, et al. JACC 2015; 65(24): Combined data set of all PROTECT AF and PREVAIL SH AG NOV2016

27 WATCHMAN TM Device Reduces Ischemic Stroke Over No Therapy Ischemic Stroke (Events/100 Patient- Years) 79% Relative Reduction 67% Relative Reduction 83% Relative Reduction Baseline CHA 2 DS 2 -VASc = 3.5 Baseline CHA 2 DS 2 -VASc = 3.8 Baseline CHA 2 DS 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 AG NOV2016

28 Price, M. J., V. Y. Reddy, et al. JACC: CV Interv 2015; 8(15): SH AG NOV2016 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 Post Procedure Destination Implant 45 days* 6 months *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 Bleeding Rate (n events/n at risk) 11.3 (43/382) 11.3 (43/381) 9.7 (35/360) Long-term warfarin (n=382) Event Rate per 100 ptyrs (n events / N at risk) 3.6 (43/1187) 3.6 (43/1180) 3.5 (35/1004) Rate Ratio P value <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.

29 Bleeding Outcomes after Left Atrial Appendage Closure Compared with Longterm Warfarin Freedom of Major Bleeding Over 3 Adjunctive Pharmacotherapy Intervals 72% >6 months post-procedure Price, M. J., V. Y. Reddy, et al. JACC: CV Interv 2015; 8(15): p < SH AG NOV2016