1. David R. Holmes, Jr., M.D. Mayo Clinic, Rochester
LAA: Who and When
David R. Holmes, Jr., M.D.
Mayo Clinic, Rochester
CRT 2016
Washington, D.C.
February 2016
test

2. Presenter Disclosure Information
David R. Holmes, Jr., M.D.
“LAA: Who and When”
The following relationships exist related to this presentation: Both Mayo Clinic and I have a financial interest in technology related to this research. That technology has been licensed to Boston Scientific.

4. Confirms Role of LAA in CVA Event-free probability
Proof of Concept
Device
Intent-to-Treat
All Stroke
Randomization allocation (2 device:1 control)
WATCHMAN
Control
Key Implication:
Confirms Role of LAA in CVA
Event-free probability
900 patient-year analysis
Days
244
147 52 12
463
270 92 22
Holmes et al, Lancet 2009

5. PROTECT AF/PREVAIL Meta-Analysis: WATCHMAN Comparable to WarfarinHR P
Efficacy
0.79
0.22
All stroke or SE
1.02
0.94
Ischemic stroke or SE
1.95
0.05
Hemorrhagic stroke
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
Hazard Ratio (95% CI)

6. 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

7. The Centers for Medicare & Medicaid Services (CMS) covers percutaneous left atrial appendage closure (LAAC) for non-valvular atrial fibrillation (NVAF) through Coverage with Evidence Development (CED) under 1862(a)(1)(E) of the Social Security Act with the following conditions:
LAA closure devices are covered when the device has received Food & Drug Administration (FDA) Premarket Approval (PMA) for that device’s FDA-approved indication and meet all of the conditions specified below:
CHADS2 – ≥2
CHADS2DS2-VASc – ≥3
Shared decision making with independent non- interventional MD
Suitable for short-term AC but deemed unable or unsuitable for long-term
Trained physicians
Enrolled in a registry

9. NOACS

10. ORBIT AF Trial OAC Contraindications
CHA2DS2-VASc
Contraindication
Overall
(n=1330)
<2 (n=81)
≥2 (n=1249) P
Prior bleed
27.7
13.6
28.7
0.003
Patient refusal
27.5
48.2
26.2
<0.0001
High bleeding risk
18.0
6.2
18.7
0.004
Frequent falls/frailty
17.6
2.5
18.6
0.0002
Need for dual APT
10.4
4.9
10.7
0.10
Unable to adhere
6.0
0.95
Comorbid illness
5.3
5.4
0.24
Prior intracranial hemorrhage
5.0
3.7
0.59
Allergy
2.4
2.3
0.43
Occupational risk
0.8
0.7
0.09
Pregnancy
0.2
0.0
0.66
Other
12.6
24.7
11.8
0.001
O’Brien et al: Am Heart J 167:601-9, 2014

11. ASAP-TOO Study Design Prospective, randomized, multi-center, global
Non-valvular atrial fibrillation deemed not suitable for oral AC to reduce the risk of stroke with CHA2DS2VASC ≥2
Randomized 2:1 (Watchman vs Control)
ASA & Plavix Group Sequential Design
Allows early looks; potential to stop early for benefit
900 subjects at up to 100 global sites
Follow-Up
45 Day with TEE
6,18 month phone visit
12 month with TEE
Years 2-5 annually
Brain imaging required at baseline if prior stroke or TIA

12. ASAP-TOO Efficacy Composite: All cause mortality CV mortality Stroke
Systemic embolism
Significant bleeding
Statistical assessment:
Non-inferiority or superiority

13. Novel Oral Anticoagulants Discontinuation and Bleeding Rates
Treatment
Discontinuation rate in study (%)
Major bleeding
(rate/year) (%)
Dabigatran1 (150 mg) 21
3.1
Rivaroxaban2 24
3.6
Apixaban3 22
2.1
Connolly SJ: N Engl J Med, 2009
Patel MR: N Engl J Med, 2011
Granger CB: N Engl J Med, 2011

14. LAAC + NOACS Prospective, randomized, multicenter, global
Non-valvular AF at risk for stroke
CHA2DS2VASc ≥2
Randomization 2:1 (Watchman vs NOAC)
Group sequential design
Allows early looks
900 subjects
Follow-Up
45 Day with TEE
6,18 month phone visit
12 month with TEE
Years 2-5 annually
Brain imaging required at baseline if prior stroke or TIA

15. LAAC + NOACS Efficacy Composite: All cause mortality CV mortality
Stroke
Systemic embolism
Significant bleeding
Statistical assessment:
Non-inferiority or superiority
Bayesian design

16. A Twofer

17. Twofer Prospective registry, multicenter, global
Patients with non-valvular AF at risk for stroke CHA2DS2VASc ≥2 undergoing
TAVR (n=100)
Atrial fibrillation ablation (n=100)
Endpoints
Early stroke
Embolization
Bleeding
Death
Pericardial effusion
Late stroke

18. NOACS

19. Stroke and Atrial Fibrillation Alternative to Warfarin or NOACS
Patients who could be treated with warfarin/NOACS
Patients who choose not to be treated with warfarin/NOACS
Contraindications to warfarin/NOACS
Patients treated with DAPT
In concert with ablation