Congresso SBHCI - 2014
Julho, Porto Alegre-RS
Terapia antiplaquetária dupla
após o implante de SF
contemporâneos: onde estamos?
Fausto Feres
São Paulo- Brazil
Instituto Dante Pazzanese de Cardiologia
Terapêutica Antiplaquetária Dupla
após SF contemporâneo
n  How
did we get to 12 months in
the first place?
DAPT with first generation DES
§ 
§ 
§ 
§ 
§ 
Bare metal stents – one month
FIM 1999 (Cypher, sirolimus) – two months
RAVEL 2002 (Cypher, sirolimus) – three months
SIRIUS 2003 (Cypher, sirolimus) – three months
TAXUS IV 2004 (Taxus, paclitaxel) – six months
Up to
2006:
Smith SC, et al. J Am Coll Cardiol. 2006;47:216-35
Late and Very Late Stent
Thrombosis: A “New” Phenomenon
Feres F et al. Catheter Cardiovasc Interv. 2006; 68:83-88
A New Mechanism
Late Acquired Incomplete Stent Apposition
Cypher SES 1216 days pos procedure
Taxus PES 331 days pos procedure
Feres F et al. Catheter Cardiovasc Interv. 2006; 68:83-88
2007 Updated Guideline
King SB, et al. J Am Coll Cardiol. 2008;51:172-209
Guidelines: US & EUROPE
Levine GN. Circulation 2011;124:e574-e651
Wijns W. European Heart Journal 2013
Terapêutica Antiplaquetária Dupla
após SF contemporâneo
n  How
did we get to 12 months in
the first place?
n  Limitations of prolonged DAPT
Limitations of prolonged DAPT
•  Cost
•  Convenience
•  Bleeding
Limitations of prolonged DAPT
•  Cost
•  Convenience
•  Bleeding
PLATO: Major Bleeding
5.5%- 1st month
15
Major Bleeding
PLATO Criteria (%)
Ticagrelor
11.6%
Clopidogrel 11.2%
10
5
P=0,43
HR: 1,04 ( IC 95%, 0,95–1,13)
0
0
60
120
180
240
300
360
Days after 1st dose
No
Ticagrelor
9.235
7.246
6.826
6.545
5.129
3.783
3.433
Clopidogrel
9.186
7.305
6.930
6.670
5.209
3.841
3.479
Ambos os grupos incluiram AAS
Wallentin L, et al. N Engl J Med. 2009;361:1045–1057.
P=NS
Scottish Coronary
Revascularization Registry
17.797 Stented Pts
2003 - 2007
Non-Cardiac Surgery
1953 pts (11%)
BMS
1383
DES
570
4.4%
within
1st year
ORTHO
COSMETIC
DIGEST
VASCULAR
Gruden NLM Circ Cardiovasc Interv. 2010;3:236-42
33%
19%
16%
10%
Terapêutica Antiplaquetária Dupla
após SF contemporâneo
n  How
did we get to 12 months in
the first place?
n  Limitations of prolonged DAPT
n  Does the DES type make a
difference?
Does the DES type make a difference?
Raber, L. et al. Circulation 2012
Terapêutica Antiplaquetária Dupla
após SF contemporâneo
n  How
did we get to 12 months in
the first place?
n  Limitations of prolonged DAPT
n  Does the DES type make a
difference?
n  What is the current evidence
for shorter DAPT?
Scientific Evidence
Early Discontinuation DAPT post DES
Randomized Trials
EXCELLENT
PRODIGY
RESET
OPTIMIZE
Registries
Metanalysis
Everolimus
(Xience V)
4 Randomized
Trials
Zotarolimus
(Resolute)
Scientific Evidences
Early Discontinuation DAPT post DES
Randomized Trials
EXCELLENT
PRODIGY
RESET
OPTIMIZE
Registries
Metanalysis
Everolimus
(Xience V)
4 Randomized
Trials
Zotarolimus
(Resolute)
EXCELLENT
EXCELLENT: DAPT- 6 vs 12 m
1.443 pacientes tratados com SF de 1ª vs. 2ª gerações
EP 1ário: morte cardíaca, IAM e revascularização do vaso-alvo
Gwon et al. Circulation 2012;125:505-513
PRODIGY Trial : DAPT 6 vs 24 m
Valgimigli al. Circulation 2012;125:2015-2026
PRODIGY: DAPT 6 vs 24 m
~2.000 pts randomized (1:1), 75% ACS
4 stent types (1:1:1:1) – BMS & DES 1ª e 2ª generation
10.1% vs. 10.0%
EP 1ário: morte, IAM, AVE
Valgimigli al. Circulation 2012;125:2015-2026
RESET Trial
Kim et al. J Am Coll Cardiol 2012;60:1340-1348
RESET: DAPT 3 vs 12 m
Cardiac Death, AMI, ST, TVR and Bleeding
Kim et al. J Am Coll Cardiol 2012;60:1340-1348
OPTIMIZE
F Feres and coauthors for the OPTIMIZE
Trial Investigators"
"
Three vs Twelve Months of Dual Antiplatelet
Therapy After Zotarolimus-Eluting Stents:
The OPTIMIZE Randomized Trial"
"
Published online October 31, 2013!
"
"
Available
jama.com
and
Availableatat
jama.com
mobile.jamanetwork.com!
mobile
jamanetwork.com
"
"
jamanetwork.com
OPTIMIZE:
A Prospective, Randomized Trial
of 3 Months Versus 12 Months
of Dual Antiplatelet Therapy with the
Endeavor Zotarolimus-Eluting Stent
•  Fausto Feres, MD, PhD
•  On behalf of the OPTIMIZE Trial Investigators
•  Instituto Dante Pazzanese de Cardiologia
•  São Paulo, Brazil
33 Clinical Sites in Brazil
n: 3119 pts
Dr. Fausto Feres (624pts)
Dr. Roberto Botelho (180pts)
Dr. João Eduardo Tinoco (446pt)
Dr. Décio Salvadori Jr. (166pts)
Dr. José A. Mangione (280pts)
Dr. Marcos Gusmão (160pts)
Dr. Hélio Castello Junior (135pts)
Dr. Eduardo Nicolela Jr. (125pts)
Dr. Marco Perin (117pts)
Dr. Fernando Devito (106pts)
Dr. J. Antônio Marin-Neto (100pts)
Dr. George Meireles (91pts)
Dr. André Labrunie / Dr. Marden Tebet (70pts)
Dr. Nelson Moura de Araújo (58pts)
Dr. Andrés Sanchez (55pts)
Dr. Sérgio Berti (52pts)
Dr. Pablo Teixeirense (49pts)
Dr. Adrian Kormann (41pts)
Dr. Rone Padilha (40pts)
Dr. Rogério Sarmento Leite (35pts)
Dr. Augusto Lima Filho e Dr. André Lima (32pts)
Dr. Marcio A. dos Santos (24pts)
Dr. Helman Martins (24pts)
Dr. Gilberto Nunes (21pts)
Dr. Paulo Marra da Motta (21pts)
Dr. Heloísa Guimarães (17pts)
Dr. Luiz E. São Thiago (15pts)
Dr. Paulo Caramori (13pts)
Dr. Alexandre Zago (9pts)
Dr. Jamil A. Saad (6pts)
Dr. Edmur Araújo (5pts)
Dr. Ari Mandil (2pts)
1st Investigator Meeting
November/2009
Primary Endpoint: NACCE at 1 Year
(All-Cause Death, MI, Stroke, Major Bleeding)
Cumulative Incidence
of NACCE (%)
15
12M DAPT
No. at risk
No. events
No. at risk
No. events
Non-inferiority
P-value = 0.002
10
Log-Rank P = 0.84
HR 1.03 (0.77 – 1.38)
6.0
5.8
5
0
Month
3M DAPT
0
3
6
9
Time After Initial Procedure (Months)
12
0
1
3
6
12
1563
18
1556
16
1520
25
1514
25
1504
11
1497
11
1468
18
1466
16
1384
21
1381
22
Landmark at 3M: NACCE
(All-Cause Death, MI, Stroke, Major Bleeding)
Incidence of NACCE (%)
15
12M DAPT
P = 0.86
HR 1.03
(0.71 – 1.51)
10
5
0
Month
No. at risk
No. events
No. at risk
No. events
3M DAPT
P = 0.91
HR 1.03
(0.66 – 1.60)
3.5
3.3
0
0
1563
18
1556
16
2.6
2.6
3
6
9
Time After Initial Procedure (Months)
1
1520
25
1514
25
3
1504
11
1497
11
6
1468
18
1466
16
12
12
1384
21
1381
22
Stent Thrombosis vs. Bleeding
ARC Def./Prob. Stent Thrombosis
Any Bleeding*
10
10
Incidence (%)
3M DAPT
12M DAPT
P = 0.64
HR 0.81
(0.34-1.96)
5
P = 0.18
HR 3.97 (0.44-35.49)
P = 0.78
HR 0.93
(0.56-1.54)
5
0.7
0.6
3
6
9
No at risk
1.0
0.4
0
12
0
3
Time After Initial Procedure (months)
Month
P = 0.07
HR 0.43 (0.16-1.11)
2.0
1.9
0.3
0.1
0
0
3M DAPT
12M DAPT
6
9
12
Time After Initial Procedure (months)
0
1
3
6
12
1563
1555
1540
1506
1505
Month
No at risk
0
1
3
6
12
1563
1538
1516
1482
1439
No events
0
6
3
4
0
No events
4
15
10
4
2
No at risk
1556
1541
1525
1501
1500
No at risk
1556
1528
1501
1472
1387
No events
5
3
3
1
0
No events
11
8
12
6
8
*Any bleeding according to the combined REPLACE-2 and GUSTO criteria.
Scientific Evidences
Early Discontinuation DAPT post DES
Randomized Trials
EXCELLENT
PRODIGY
RESET
OPTIMIZE
Registries
Metanalysis
Everolimus
(Xience V)
4 Randomized
Trials
Zotarolimus
(Resolute)
Everolimus (Xience V)
Taxa de TS até 12 meses, %
Análise post-hoc envolvendo ~10.615 pacientes incluídos
nos estudos SPIRIT V and Women, and Xience V USA and
India4 (mundo real), avaliando TS def./prov. (ARC)
4
SEM interrupção de TAD
COM interrupção de TAD
3
2
1
1,64
1,63
0,68
0,68
0,21
0
0-3 Meses
0,29 0,2
0
3-12 Meses
0-1 Mês
Palmerini T. at TCT 2012, Miami, EUA
1-12 Meses
Zotarolimus (Resolute)
Taxa de TS até 12 meses, %
Análise post-hoc envolvendo ~5.000 pacientes incluídos
nos estudos RESOLUTE All-Comers, International, US e
Japão (30% diabéticos), avaliando TS def./prov. (ARC)
4
SEM interrupção de TAD
COM interrupção de TAD
2,96
3
1,92
2
1
0,78
0,67
0,1
0
0-3 Meses
0,21
0
3-12 Meses
0-1 Mês
Bhatt D. at TCT 2013, San Francisco, EUA
0
1-12 Meses
Scientific Evidences
Early Discontinuation DAPT post DES
Randomized Trials
EXCELLENT
PRODIGY
RESET
OPTIMIZE
Registries
Metanalysis
Everolimus
(Xience V)
4 Randomized
Trials
Zotarolimus
(Resolute)
Terapêutica Antiplaquetária Dupla
após SF contemporâneo
• 
Recent studies are consistent that shorter
DAPT duration post 2nd generation DES
might not always require 12 months DAPT
to reduce the risk of adverse thrombotic
events.
•  These outcomes may be especially relevant
for patients who are at high risk of bleeding
complications following PCI, such as the
elderly and patients with a history of
hemorrhagic events, who might need to stop
DAPT earlier.