Is there an alternative strategy?
Prof. Corrado TamburinoCardiovascular Department, Ferrarotto Hospital,
University of Catania, Catania, Italy
Optimal DAPT choices for high-bleeding risk patients- A challenging ACS - STEMI patient -
Speaker's name: Corrado Tamburino
I have the following potential conflicts of interest to report:
Receipt of honoraria or consultation fees: Abbott, Biosensors, Medtronic, Symetis
Potential conflicts of interest
High bleeding risk patients: Trial criteria
Age ≥ 75 years OAC planned after PCI Baseline Hb < 11g / dl or transfusion during prior 4 weeks Planned major surgery (within next year) Cancer diagnosed or treated ≤ 3 years Creatinine clearance < 40 ml / min Hospital admission for bleeding during past year Thrombocytopenia (< 100.000 / mm3) Any prior intra-cerebral bleed Any stroke during the past year Severe liver disease NSAID or steroids planned after PCI Anticipated poor DAPT compliance for other medical reason
High bleeding risk patients: DAPT score
Yeh RW et al. JAMA 2016;315:1735-1749
Variables Points
Age < 65 years 0
Age 65 - <75 -1
Age ≥ 75 - 2
Vein graft PCI 1
Current or prior smoking 1
Diabetes mellitus 1
MI at presentation 1
Stent diameter < 3 mm 1
Prior CHF or LVEF <30% 2
Prior PCI or Prior MI 1
Paclitaxel-eluting stent 1
High bleeding risk patients: DAPT score < 2 (Low)
Yeh RW et al. JAMA 2016;315:1735-1749
ST/MI Bleeding
High bleeding risk patients: PRECISE-DAPT score
Costa F et al. Lancet 2017; 389:1025-1034
High thrombotic risk characteristics
NSTEMI/STEMI Low EF Diabetes, CKD Bifurcation, Long lesions, small vessels Calcified lesion-rotablation Planned surgery within 12 months after PCI Cancer Hematological disorders determining a
prothrombotic state Poor DAPT adherence
ACS/ More Complex Lesions Age/More Comorbidities
Thrombotic Risk Hemorragic Risk
Prolonged DAPT ? Reduced DAPT ?
More Bleeding More Thrombosis?
Squaring the circle in high bleeding and thrombotic risk
An Optimal antiplatelet regimenand a safe DES are needed
Strategies on high thrombotic and bleeding risk
Procedural optimization – the key role of
intravascular imaging
Short DAPT
Stent selection
Strategies on high thrombotic and bleeding risk
Procedural optimization – the key role of
intravascular imaging
Short DAPT
Stent selection
Lesion preparation is key to achieve good DES expansion in calcified lesions
Devices for lesions preparation
Ultra-low profile balloons
Semi compliant balloons
NC Balloons
High pressure OPN NC balloons
Scoring balloons
Cutting balloons
Atherectomy
Preparation strategy in calcified lesions
IVUS
Non-circumferential calcification< 270° calcium arc
Circumferential calcification> 270° calcium arc
NC balloon dilatationBalloon escalation strategy
Atherectomy
Scoring, OPN balloon, Cutting
Residual stenosis > 40%
Residual stenosis > 40%
IVUS pre-procedural role for LM PCI
Assessment of intermediate lesions
Sizing
Plaque distribution
Procedural plan
To determine when and how much to debulk
Considerations for LM stenting technique in a high
bleeding risk patient
One stent technique
Less metal
Less complicated stenting
Trends towards better outcomes in overall bifurcations
Two-stent technique
Preferable as:
LCx > 2.75 mm
Critical LCx ostialstenosis > 5 mm
Severe calcification
My proposed strategy: IVUS guided two-stent technique(Preference for TAP or mini-crush)
IVUS-guided optimization – Criteria for stentunderexpansion at the distal LM bifurcation
Kang S et al. Circ Card Interv 2011;4:562-569
Ferrarotto HospitalAOU Policlinico-Vittorio EmanueleCatania, Italy
De La Torre-Hernandez et al.
J Am Coll Cardiol Intv. 2014;7:244-254
Impact of IVUS on Left Main PCI Outcomes505 Propensity-Matched Pairs From 1,670 Patients Undergoing Left Main PCI
In the Spanish, Multicenter (N=51) IVUS-TRONCO-ICP Registry
After matching
3-Year FUIVUS
(N=505)
No IVUS
(N=505)P value
All-Cause Death 7.4% 13.0% 0.01
CV Death 3.3% 6% 0.07
MI 4.5% 6.5% 0.4
TLR 7.7% 6.3% 0.7
CV Death/MI/TLR 11.7% 16% 0.04
ST 0.6% 2.2% 0.04
Benefit pronounced in distal left main disease and patients treated with 2-stent strategies
Strategies on high thrombotic and bleeding risk
Procedural optimization – the key role of
intravascular imaging
Short DAPT
Stent selection
DAPT duration: guidelinesrecommendations
ESC NSTE-ACS 2015 Class Level
P2Y12 inhibitor administration for a shorter duration of 3-6 months after DES implantation may be considered in patients deemed at high bleeding risk
IIb A
ESC Myocardial Revascularization 2014 Class Level
Shorter DAPT duration (< 6 months) may be considered after DES implantation in patients at high bleeding risk
IIb A
Roffi M, et al. 2015 ESC Guidelines for Management of ACS. EHJ 2015 (Online Aug 29, 2015). Windecker S, et al. 2014 ESC/EACTS Guidelines on Myocardial Revascularization. EHJ 2014;35:3541-619.
DAPT duration in high bleeding riskpatients
There no studies on DAPT duration in high bleeding risk patients
HBR patients were excluded from studies on which the guidelines recommendations on DAPT duration are based
Individualized treatment in clinical practice
Strategies on high thrombotic and bleeding risk
Procedural optimization – the key role of
intravascular imaging
Short DAPT
Stent selection
Biofreedom as alternative stent? LEADERS FREE: Trial Design
Prospective, double-blind randomized (1:1) trial2466 High bleeding risk (HBR) PCI patients
vs.
DAPT mandated for 1 month only, followed by long-term SAPT
BioFreedom™ DCS
Gazelle™BMS
• Primary safety endpoint:Composite of cardiac death, MI, definite / probable stent thrombosisat 1 year (non-inferiority then superiority)
• Primary efficacy endpoint:Clinically-driven TLR at 1 year (superiority)
LEADERS FREE: Primary Safety Endpoint(Cardiac Death, MI, ST)
0
90 180 270 390
Cu
mu
lati
ve P
erce
nta
ge o
f Ev
ent
(%)
3
6
9
12
Days0
12.9%
9.4%
p = 0.005 for superiority
15
Number at Risk
DCS 1221 1146 1105 1081 1045
BMS 1211 1115 1066 1037 1000
DCS with short DAPT VS.
DCS with prolongedDAPT?
A 1-month DAPT regimen with UltimasterDES has been CE-approved
Patients should be maintained on clinically adequate post-procedural antiplatelet therapy (aspirin, thienopyridine, or
other appropriate antiplatelet agents) according to the current guidelines.
In case of need, dual antiplatelet therapy can be discontinued earlier, but not before one month.
DAPT, dual antiplatelet therapy.
Ultimaster instructions for use. 2014-10
Safety of Ultimaster in high risk populationsCardiac death & MI at 2-year follow-up
5.7
2.4
4.1
6.0
3.3
6.55.9
6.4
7.77.2
0
1
2
3
4
5
6
7
8
9
DiabetesMellitus
High risk ACS MV Disease Long lesions Bifurcation
Ultimaster Xience
%
P=NS
High risk ACS: STEMI+NSTEMI
CENTURY II
CENTURY II Severe calcification versus moderate/mild/none
TLF at 4 years
Moderate/mild/none7.90%
[6.41% ; 9.71%]
Severe calcification
18.42% [11.35% ; 29.11%]
N°=1040
N°=76
CENTURY II Severe cacification versus moderate/mild/none
TLF at 4 years
Xience24.24%
[12.94% ; 42.67%]
Ultimaster13.95%
[6.52% ; 28.45%]
N°=33
N°=43
MASTER DAPT TRIAL: study design
≈4300 high bleeding risk patientstreated with Ultimaster DES
DAPT discontinuation
DAPT continuation(at least 11 months)
Primary Endpoint at 11 months after randomization Net adverse clinical endpoints (NACE) defined as a composite of all-cause
death, myocardial infarction, stroke and bleeding events MACCE defined as a composite of all-cause death, myocardial infarction and
stroke Major or clinically relevant non-major bleeding defined as a composite of type
2, 3 and 5 BARC bleeding events
R
1 Month after PCI
Closing remarks
In HBR patients with high-thrombotic risk (i.e. STEMI, complex lesions) it is reasonable to shorten DAPT (< 6 months) under these conditions:
Optimal procedural results confirmed by intravascular imaging
Use of a new generation DES with a good safety profile, especially in high-risk subgroups
The MASTER DAPT trial will be the first large trial providing insights on the DAPT duration after DES (Ultimaster) in HBR patients.
Baseline characteristicsLEADERS-FREE vs. e-Ultimaster
DCS (%)
N°=1239
BMS (%)
N°=1227
e-Ultimaster
N°=1643
Mean age 75.7 ± 9.4 75.7 ± 9.3 74.7 ± 9.4
Female gender 29.8 30.9 31.5
BMI 27.5 ± 4.8 27.2 ± 4.6 27.5 ± 4.5
Diabetes 34.0 32.3 32.0
NSTEMI presentation 22.4 23.2 28.1
STEMI presentation 4.7 4.0 16.8
Prior MI 19.6 21.4 24.3
Prior PCI 22.2 21.9 28.4
Prior CABG 9.4 10.1 8.3
Multivessel CAD 62.9 61.6 52.6
Index procedureLEADERS-FREE vs. e-Ultimaster
DCS (%)N°=1239
BMS (%)N°=1227
e-UltimasterN°=1643
Radial access 60.7 58.7 80.2
Number of treated lesions / patient
1.6 ± 0.8 1.6 ± 0.9 1.5 ± 0.8
LMS 3.0 3.9 3.8
SVG 1.4 1.8 2.2
Bifurcation 14.9 16.0 15.4
ISR 2.4 2.6 5.9
CTO 5.0 4.4 4.6
Mean total implanted
stent length / patient34.5 ± 23.1 33.4 ± 23.4 34.2 ± 23.3
Mean number of stents
implanted / patient1.9 ± 1.1 1.8 ± 1.2 1.6 ± 0.9
Device success 97.7 97.6 99.6
5.1
9.8
1.3
0.0
2.0
4.0
6.0
8.0
10.0
12.0
Clinically driven TLR
DCS BMS e-Ultimaster
%
Clinically driven TLR at 12 MonthLEADERS-FREE vs. e-Ultimaster
4.2
6.1
2.0
5.3
8.9
2.2
3.5
2.1
1.3
0.0
1.0
2.0
3.0
4.0
5.0
6.0
7.0
8.0
9.0
10.0
Cardiac death MI Definite + probable ST
DCS BMS e-Ultimaster
%
Components of safety endpointLEADERS-FREE vs. e-Ultimaster
