TAVI and Adjunctive Pharmacological Therapy: … and Adjunctive Pharmacological Therapy: Current...

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.


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


Stroke/ Embolism

0,9 0,9

2,7

0

0,5

1

1,5

2

2,5

3


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.


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

TAVI and Adjunctive Pharmacological Therapy: … and Adjunctive Pharmacological Therapy: Current...

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