1. Role of LAA Occlusion in Patients With Atrial Fibrillation After PCI Marco Mennuni, MD Interventional Cardiologist Hopital Europeen George Pompidou, Paris (France)

2. Disclosure Statement of Financial Interest
Within the past 12 months, I or my spouse/partner have had a financial interest/arrangement or affiliation with the organization(s) listed below.
Affiliation/Financial Relationship
Company
Grant
Consulting Fees
EAPCI - European Society of Cardiology
Boston Scientific

3. Epidemiology of atrial fibrillation and PCI in US and EU
20 Million people with AF (1-2% of population)
16 Million anticoagulation indicated (80%)
4.8 Million have CAD as well (20%-45%)
1- 2 Million potential revascularization (20%-25%)
The AFFIRM Investigators. Am Heart J 2002;143:991–1001;
Carpodanno D et al, Circ Cardiovasc Interv 2014;7:113–124;
Kralev S et al, PLoS One 2011;6:e24964;
Bahit MC et al, Int J Cardiol 2013;170:215–220

4. Stroke in AF and ACS are mediated by a thrombotic process
Coronary/stent thrombosis
Stroke +
DAPT
OAC
Bleeding

5. HR for Risk of Bleeding
Arch Intern Med. 2010;170(16):

6. AVIATOR registry: 900 pts with Afib undergoing PCI Triple therapy at discharge among different risk strata
Highest Risk *
p = NS * * *
% of patients on TT
p<0.01 for trend
HAS-BLED score
CHADS2 score
Lowest risk
Mennuni et al Am J Cardiol Jul 1;116(1):37-42

7. Bleeding and mortality
Increased HR of mortality at 1 y, after bleeding post-PCI
Mehran et al JACC Cardiovasc Interv Jun;4(6):

8. How to manage the high bleeding risk…
Evidence suggestion:
to drop off Aspirin from TT (WOEST trial)
Reduce the duration of TT at 1 month (ISAR-triple trial)
The problems:
Both trials not powered for ischemic events
In WOEST, the primary endpoint was driven by minor bleedings
DAPT benefit in ACS patients is well established
ESC Guidelines on AF. Eur Heart J 2016; 37:
ACC/AHA Guidelines on AF. Circulation 2014; 130:
Bhatt et al JACC 2015

9. NOACs and antiplatelets are just empirical…
Recommendations on combined use of
NOACs and antiplatelets are just empirical…
RE-LY
Dabigatran
ROCKET- AF
Rivaroxaban
ARISTOTLE
Apixaban
ENGAGE
Edoxaban
Concomitant use of aspirin alone
32%
≈37%
≈31%
≈29%
Concomitant use of clopidogrel alone
≈2%
<2%
Concomitant use of DAPT
≈5%
Excluded
Capodanno D, et al. EuroIntervention. 2015;10:

10. Requiring Medical Attention (%)
Except for Rivaroxaban. PIONEER Trial adds a new alternative to reduce bleeding in Afib patients undergoing PCI.
TIMI Major, TIMI Minor, or Bleeding
Requiring Medical Attention (%)
26.7%
VKA+ DAPT
VKA+ DAPT
18.0%
16.8%
Riva + DAPT
Riva + DAPT
Riva + P2Y12
Riva + P2Y12
Riva + P2Y12 v. VKA + DAPT
180
360
Days
Gibson et al. N Engl J Med Dec 22;375(25):

11. The New Oral Anticoagulants work better than Warfarin but …
They are good, but they are still coagulation blockers, with an intrinsic rate of bleeding events which increase permanently over the time
2) They have a not negligible discontinuation rate
Study
Treatment
Major Bleeding
Discontinuation in the study
RE-LY
Dabigatran (110mg)
2.71 %
20.7 %
Dabigatran (150mg)
3.11 %
21.2 %
Warfarin
3.36 %
16.6 %
ROCKET-AF
Rivaroxaban
3.6 %
23.7%
3.4 %
22.2 %
ARISTOLE
Apixaban
2.13 %
25.3 %
3.09 % nc
ENGAGE AF
Edoxaban HD
2.7%
34%
Edoxaban LD
1.6%
32%
3.4%

12. May be LAA Occlusion in AF Patients undergoing PCI an Option?
Evidence available is weak
1) ACP Registry (1,000 patients treated with Watchman)
36% with CAD and 22% with previous PCI. No further analysis performed.
2) Single center series:
15 patients with AF undergoing PCI for acute coronary syndrome.
Procedural success in 14/15 patients (1 pericardial effusion before transeptal without implantation of the device).
No peri-procedural major adverse events.
At a 6 months follow-up 1 peri-procedural minor bleeding and 2 non-CV death.
LAA occlusion in AF and PCI patients is based on empirical data.
Ciccarelli G et al., Int J Cardiovasc Res 2017; 6, 1
Tzikas A et al.,EuroIntervention 2016;11:

13. Comparison between LAA Occlusion and Warfarin
Pooled analysis of 1100 pts from 2 RCTs that compared WATCHMAN LAA closure with long-term warfarin therapy in AF.
Overall: Bleeding Events
Post Procedure: Bleeding Events
p = ns
Overall bleeding rates similar
p = 0.002
51% reduction in bleeding events in WATCHMAN device arm
Price MJ et al., J Am Coll Cardiol Interv 2015,

14. Indirect Comparison between LAA Occlusion and NOACs
Network meta-analysis of 19 RCTs with a total of 87 831 patients with AF receiving anticoagulants, APT, placebo or LAAC.
LAA occlusion
NOAC
Antiplatelet
VKA
ShwetSahay et al. Heart 2017;103:

15. Comparison between LAA Occlusion and NOACs for Mortality and Stroke
Shweta Sahay et al. Heart 2017;103:

16. Comparison between LAA Occlusion and NOACs
for Bleeding Events
Shweta Sahay et al. Heart 2017;103:

17. Implant Procedure Safety
7-Day SAEs procedure-related in WATCHMAN studies.
2.8%
SAE: Serious Adverse Event - Composite of vascular complications includes cardiac perforation, pericardial effusion with tamponade, ischemic stroke, device embolization, and other vascular complications.
PROTECT AF/CAP: Reddy et al. Circulation 2011
PREVAIL: Holmes et al. JACC 2014

18. PARIS Risk Score for Ischemic and Bleeding Events
Which patients could be a potential candidate for
LAA occlusion after PCI?
PARIS Risk Score for Ischemic and Bleeding Events
Data from 4,190 patients treated with DES and enrolled in the PARIS registry externally validated.
Baber U et al., JACC 2016

19. DAPT study Predictors of Net Treatment Effect
Characteristics
Impact on Net Treatment Effect
% of Variation Explained
Age ≥ 75
Age 65 - < 75
Age < (reference)
-1.2%
-0.5% -
6.0%
2.1%
Prior PCI or MI
1.1%
14.6%
Stent Diameter < 3 mm
0.9%
10.1%
CHF or LVEF < 30%
1.9%
9.9%
MI at Presentation
1.0%
9.6%
Paclitaxel-Eluting Stent
8.8%
Cigarette Smoker
0.7%
4.3%
Diabetes
0.6%
Vein Graft PCI
1.6%
3.7%
Hypertension
0.2%
0.4%
Renal Insufficiency
0.3%
PAD
-0.1%
0.04%
Bleeding
Predictors
Ischemia
Predictors
Bleeding
and
Ischemia
Predictors

20. The DAPT Score Distribution of DAPT Scores among all
randomized subjects in the DAPT Study
Variable
Points
Patient Characteristic
Age
≥ 75 -2
65 - <75 -1
< 65
Diabetes Mellitus 1
Current Cigarette Smoker
Prior PCI or Prior MI
CHF or LVEF < 30% 2
Index Procedure Characteristic
MI at Presentation
Vein Graft PCI
Stent Diameter < 3mm

21. Continued Thienopyridine vs Placebo after 12 months
DAPT Score <2 (Low); N=5731
DAPT Score ≥ 2 (High); N=5917
Death, MI, or Stroke (MACCE)
Death, MI or Stroke (MACCE)
10%
Continued Thienopyridine Placebo
10%
Continued Thienopyridine Placebo 8% 8% 6% 6%
4.9% vs. 7.6%
P<0.001
Cumulative Incidence of MACCE
Cumulative Incidence of MACCE 4%
3.7% vs. 3.8%
P=0.73 4% 2% 2% 0% 0% 12 15 18 21 24 27 30 12 15 18 21 24 27 30
Months After Enrollment

22. Conclusions
In patient with AF, need of DAPT, and high risk of bleeding LAA occlusion may represents a therapeutic option to reduce risk of stroke and bleeding at long-term follow-up.
Potential candidate for LAA occlusion might be patients with high scores (PARIS or DAPT) which identify who might benefit from prolonged DAPT.

23. Conclusions
Trials on NOACs and LAA occlusion in AF patients undergoing PCI are ongoing:
ENTRUST AF PCI (Edoxaban+P2Y12 vs TT)
AUGUSTUS (Apixaban+P2Y12+Aspirin vs TT) double randomization of (Apixaban vs Warfarin and Aspirin vs Placebo)
RE-DUAL PCI (Dabigatran+P2Y12 vs TT)
WATCHMAN vs Warfarin after PCI (results expected on Q4 2017)
Amplazter Cardiac Plug vs Dabigatran+Aspirin vs Dabigatran+Clopidogrel (not yet recruiting)
They will provide important indication on the best therapeutic strategy in this high risk population.

24. Thanks.