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TAVI and Adjunctive Pharmacological Therapy:
Current Practice and Future Perspectives
Α-Δ. ΜΑΥΡΟΓΙΑΝΝΗ
ΚΑΡΔΙΟΛΟΓΟΣ
AIMOΔΥΝΑΜIΚΟ ΕΡΓΑΣΤΗΡΙΟ
Γ.Ν.Θ. «Γ.ΠΑΠΑΝΙΚΟΛΑΟΥ»
ΘΕΣΣΑΛΟΝΙΚΗ
Disclosure Statement of Financial Interest
none whatsoever…
Evolution of Devices (2002 - 2015)Prosthesis with CE Mark Approval
EDWARDS SAPIEN THV EDWARDS SAPIEN XT SYMETIS ACURATE
TA
SJM PORTICO DIRECT FLOW
MEDICAL
BSC LOTUS EDWARDS
SAPIEN 3
MEDTRONIC
EVOLUT R
MEDTRONIC COREVALVE JENAVALVE MEDTRONIC
ENGAGER
SYMETIS ACURATE
NEO
2007 2010 2011 2012 2013 2014 2015
TAVI at the Antipodes of the Risk Spectrum:
Mortality at 30-days in FDA Approved Studies 2010 - 2015
Pilgrim T., Windecker S.
Transcatheter Aortic Valve Replacement: Lessons Gained From Extreme-Risk Patients.
J Am Coll Cardiol. 2015 Sep 22;66(12):1335-8
The Majority of AS Patients Indicated Per Guidelines
Remain Untreated
Sources: Nkomo 2006, Livanainen 1996, Aronow 1991, Bach 2007, Freed 2010, Lung 2007, Pellikka 2005, Internal estimates
Estimated U.S. AVR Penetration
In Severe, Symptomatic Patients
TAVI Present Guidelines
Indication for AVR Heart Valve Team
Low Intermediate
Surgical Risk
Surgical
AVR (I)
High
Surgical Risk
Prohibitive
Surgical Risk
TAVR
(II a)
Predicted post TAVR
Survival > 1 year
TAVR
(I)
Palliative
Care
Bridge to
TAVR or SAVR
for severe
symptoms
BAV (IIa)
Nishimura RA. et al.
2014 AHA/ACC guideline for the management of patients with valvular heart disease:
a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines.
J Am Coll Cardiol. 2014 Jun 10;63(22):e57-185
Stroke in TAVI
DAPT SINGLE ANTIPLATELET
DOACs
Stortecky S., Windecker S.
Stroke: an infrequent but devastating complication in cardiovascular interventions.
Circulation. 2012 Dec 18;126(25):2921-4
STROKE
PROTECTION
STRATEGY
MINIMAL TOUCH TECHNIQUE
EMBOLIC PROTECTION DEVICE
NEW GENERATION VALVE PROSTHESIS
INTRA AND PERIPROCEDURAL ANTITHROMBOTIC THERAPY
PTS. WITH SR
PTS. WITH AFib
Stroke in TAVI
Nombela-Franco L. et al.
Timing, predictive factors, and prognostic value of cerebrovascular events in a large cohort of patients undergoing transcatheter aortic valve implantation.
Circulation. 2012 Dec 18;126(25):3041-53
What Lies Within?
75
52 53
32
21 20
1210
0
10
20
30
40
50
60
70
80
pts.+ debris aortic wall/valve thrombusoverall
collagenoustissue
valve tissue thrombusisolated
amorphouscalcium
foreign boby
Van Mieghem NM. et al.
Histopathology of embolic debris captured during transcatheter aortic valve replacement.
Circulation. 2013 Jun 4;127(22):2194-201
TAVI: Rate of Stroke at 30 Days
0
0,5
1
1,5
2
2,5
3
3,5
4
4,5
5
SOURCE 2012 PARTNER Coh 1.2011
German Registry2011
ADVANCE 1 2012 US CORE VALVE2014
PARTNER II Si3
Petronio SA.
euroPCR 2016
2,50%
4,70%
2,80%
3,30%
4,90%
1,00%
TAVI: Neuroimaging
0
10
20
30
40
50
60
70
80
90
Rhodes Cabau JACC 2011 Ghanem JACC 2010 Arnold JACC Int. 2010 Kahlert Circulation 2010 Astarci EJCTS 2011
68.0% 68.0% 69.0%72.7%
84.0%
Daneault B. et al.
Stroke associated with surgical and transcatheter treatment of aortic stenosis: a comprehensive review.
J Am Coll Cardiol. 2011 Nov 15;58(21):2143-50
TAVI vs SAVR in High-risk Patients
New Onset Atrial Fibrillation
0
5
10
15
20
25
30
35
PARTNER 1 newonset AFIB 30 days PARTNER 1 new
onset AFIB 1 year CORE VALVE HIGHRISK new onset
AFIB 30 daysCORE VALVE HIGH
RISK new onsetAFIB 1 year
New Onset Atrial Fibrilation
TAVI SAVR
Windecker S.
euroPCR 2015
Comorbidities:
Atrial Fibrillation in TAVI Patients
0
5
10
15
20
25
30
35
40
45
50
Piazza 2008 Webb 2009 Leon 2010 Leon 2010 Smith 2011 Smith 2011 Tamburino2011
Bullesfeld2011
29
41,1
32,9
48,8
40,842,7
16,4
39,7
Stefanini G.
euroPCR 2015
Variables Mean (min–max)
Age (years) 82 (50–98)
Male sex (%) 44 (24–57)
Diabetes (%) 28 (23–35)
Hypertension 60 (36–85)
Prior coronary
disease (%)
54 (41-69)
Prior CABG (%) 25 (14-45)
Chronic renal
failure (%)
35 (20–62)
COPD (%) 26 (21–30)
Prior stroke (%) 9 (7–11)
Peripheral vascular
disease (%)
19 (7–35)
TA 30 (11–50)
TF 11 (4–19)
Porcelain aorta (%) 12 (7-18)
Frailty (%) 21 (17–25)
Mean CHADS2 score ~3
Clinical Experience – Published Registries
Patient Characteristics
TAVI and Coronary Artery Disease
59
65
73
2023
44
11
17
31
0
10
20
30
40
50
60
70
80
Gasparato et al. Wenaweser et al. Abdul Wahab et al.
CAD PCI pre TAVI DES
Gasparetto et al. CCI 2013
Wenaweser et al. Eurointervention 2012
Abdul-Wahab et al. Am J Cardio 2012
67 y/o Male Physician s/p TAVI with 29mm Sapien 3 Valve
Day 1 TTE
Gradient 10 mmHg
4 months post TAVI
Gradient 23 mmHg
Worsening shortness of breath 4 months post-TAVR
Leaflet Thickening/ Restricted Leaflet Motion Noted on 4D VR-CT
Restricted leaflet motion
Hypoattenuating lesions
Leaflet motion restored following anticoagulation with warfarin (INR 2-3)
Repeat CT performed after 3 months
Resolution of symptoms with anticoagulation
Risk of THV Thrombosis
None 0 (0/1)
(0.0–97.5)
Aspirin only 25.0 (4/16)
(7.2–52.3)
Clopidogrel only 12.5 (2/16)
(1.5–38.3)
Aspirin+clopidogrel 9.7 (19/195)
(6.0–14.8)
Warfarin only 7.1 (2/28)
(0.9–23.5)
Warfarin+aspirin 1.0 (1/96)
(0.0–5.7)
Warfarin+clopidogrel 0 (0/41)
(0.0–8.6)
Warfarin+aspirin+
clopidogrel
0 (0/6)
(0.0–45.9)
NOAC only 0 (0/5)
(0.0–52.2)
Warfarin, part of post-
TAVR
antithrombotic
therapy*
Yes 1.8 (3/171)
(0.4–5.0)
No 10.7 (25/234)
(7.0–15.4)
J Am Coll Cardiol. 2016 Nov 8;68(19):2059-2069
Transcatheter Aortic Valve Thrombosis:
Incidence, Predisposing Factors, and Clinical Implications.
Hansson NC. et al.
TAVI: Risk of Ischaemic and Bleeding Complication
Nijenhuis VJ. et al.
Antithrombotic treatment in patients undergoing transcatheter aortic valve implantation (TAVI).
Thromb Haemost. 2015 Apr;113(4):674-85
Major Late Bleeding: Etiology
40,8
15,5
7,8 6,3
3,5 2,1 2,1 2,1
1,4 0,7
23,2
0
5
10
15
20
25
30
35
40
45
Généreux P. et al.
Incidence, predictors, and prognostic impact of late bleeding complications after transcatheter aortic valve replacement.
J Am Coll Cardiol. 2014 Dec 23;64(24):2605-15
142 Major Late Bleedings
(incidence 5.9%)
AFIB and MLB after TAVI: Cumulative Risk
Généreux P. et al.
Incidence, predictors, and prognostic impact of late bleeding complications after transcatheter aortic valve replacement.
J Am Coll Cardiol. 2014 Dec 23;64(24):2605-15
Current Recommendations for Anti-Thrombotic Therapy Following
Transcatheter Aortic Valve Implantation
ACCF/AATS/SCAI/
STS
expert consensus(a)
AHA/ACC
Guidelines(b)
CCS
position statement(c)
ESC/EACTS
guidelines(d)
Long-term
anti-thrombotic
treatment
Aspirin 81 mg/day
indefinitely
Lifelong aspirin 75–
100 mg daily
(Class IIb;
level of evidence: C)
Low-dose aspirin
indefinitely
Low-dose aspirin
indefinitely
Post-procedural
anti-thrombotic
treatment
Aspirin 81 mg/
day + clopidogrel
75 mg/day for 3–6
months
If warfarin indicated
then no clopidogrel
Aspirin 75–100 mg/
day + clopidogrel
75 mg/day for
6 months
ASA 80 mg/
day + thienopyridine
for 1–3 months
If oral anticoagulant
indicated (AF),
avoid triple therapy
unless indication
exists
Low-dose aspirin + a
thienopyridine
early after TAVI
In patients in AF, a
combination of VKA
and aspirin or
thienopyridine is
generally used,
but should be
weighed against
increased risk of
bleeding
a.J Am Coll Cardiol 2012;59:1200–125
b.Circulation 2014;129:e521–e643
c.Can J Cardiol 2012;28:520–5284
d.Eur Heart J 2012;33:2451–2496
Single vs. Dual Antiplatelet Therapy Following TAVI
Iung B., Rodés-Cabau J.
The optimal management of anti-thrombotic therapy after valve replacement: certainties and uncertainties.
Eur Heart J. 2014 Nov 7;35(42):2942-9
Do We Really Need DAPT?
Hassell ME. et al.
Antiplatelet therapy following transcatheter aortic valve implantation.
Heart. 2015 Jul;101(14):1118-25
Triple Therapy Following TAVI
7,8
8,8
10,6
0
2
4
6
8
10
12
DAPT OAC+single APT OAC+DAPT
Death
1,3
0
4
0
0,5
1
1,5
2
2,5
3
3,5
4
4,5
DAPT OAC+single APT OAC+DAPT
Stroke/ Embolism
0,9 0,9
2,7
0
0,5
1
1,5
2
2,5
3
DAPT OAC+single APT OAC+DAPT
Major Bleeding
Dual antiplatelet
(n=993)
OAC + mono antiplatelet
(n=171)
OAC + dual antiplatelet
(n=237)
Zeymer U et al.
Antithrombotic therapy after transfemoral aortic valve implantation (TAVI). Potential hazard of triple therapy. (Abstract)
Eur Heart J 2011; 32 Suppl:900
AF - TAVI
Antithrombotic Treatment
PARTNER Trial (a) ACC/STS Recommendations (b) CCS Statement (c)
Preprocedural ASA 81 mg
Clopidogrel 600 mg_ _
Periprocedural UFH
ACT 250 sec
Reversal with protamine: optional
Bivalirudin- not allowed
UFH
ACT 300sec
Reversal with protamine recommended
Bivalirudin not mentioned
_
Postprocedural ASA 81 mg/ day +
Clopidogrel 75 mg/ day x 90 d
If warfarin indicated (Afib) then no
clopidogrel
ASA 81 mg/ day +
Clopidogrel 75 mg/ day x 3_6 mo.
If warfarin indicated (Afib) then no
clopidogrel
Indefinite low dose ASA generally
recommended +TNP x 1-3 mo.
If oral anticoagulant indicated (Afib), avoid
triple therapy unless definite indication
exists
a. N Engl J Med 2010;363:1597–607
a. N Engl J Med 2011;364: 2187–98
b. Am J Cardiol 2005;96:1379–83
c. J Am Coll Cardiol 2012;59:1200–54
The Future?
Pros Cons
DOACs
Apixaban/Rivaroxaban Rapid onset and predictable
anticoagulation
No antidote, > bleeding risk
Dabigatran Rapid onset and predictable
anticoagulation
No experience with antidote in
this setting
New P2Y12 inhibitors
Prasugrel Rapid onset, > potency,
<interpatient variability
Unknown if > degree of
platelet inhibition is usefull,
contraindicated if prior CVE, >
bleeding risk
Ticagrelor Rapid onset, > potency,
<interpatient variability
Unknown if > degree of
platelet inhibition is usefull,
BID dose, dyspnoea, >
bleeding risk
Rodés-Cabau J. et al.
Antithrombotic treatment in transcatheter aortic valve implantation: insights for cerebrovascular and bleeding events.
J Am Coll Cardiol. 2013 Dec 24;62(25):2349-59
Ongoing/ Upcoming Studies
Trial ARTE(a) ATLANTIS(b) GALILEO(c) POPular-TAVI(d)
Design RCT RCT RCT RCT
Planned N 200 1500 1500 1000
Study regimen Clopid 3 m
ASA 6 m
Apixaban ASA 3 m +
Rivaroxaban 12 m
Aspirin alone /
OAC alone
Control regimen ASA 6 m Standard of care
(DAPT/SAPT/OAC)
Clopid 3 m +
ASA 12 m
Aspirin/OAC +
Clopid 3m
Primary EP Death, MI, CVA or
major bleed @ 1y
Death, MI, stroke, TIA,
systemic embolism,
intracardiac or
bioprosthesis
thrombus, DVT, PE,
major bleed @ 6m
Death, stroke, MI,
valve thrombosis, PE,
DVT and systemic
embolism @1y
Any bleeding @1y
a.NCT01559298
b.NCT02664649
c.NCT02556203
d.NCT02247128