Optimal DAPT Management for

High Bleeding Risk Patients on

Non Polymer Stent
Dr Shaiful Azmi bin Yahaya, MD, Mmed, FNHAM, FAsCC, FAPSIC
Sheraton Mustika Hotel
Jogjakarta, Indonesia
Disclosure

 I have nothing to disclose

 Patients at High Bleeding Risk (HBR)
Advanced Age Cancer Anemia / Bleeding

Shortened
Recent Stroke Need for Anticoagulants Planned Surgery
DAPT
 A Acute

ACS patients >75 years, who M

I
Myocardial
Infarction in

underwent PCI (n=33,834) S Switzerland

%
 JACC 2015; 66:1046-8

Impact of bleeding and MI on mortality risk

« How do you manage a patient who is at very high risk
for bleeding requiring coronary stent implantation? »

946 interventional cardiologists

Summer 2014

EuroIntervention 2015;11:68-74
Bleeding Avoidance Strategies

1. Vascular Access
2. Choice of Stent
3. DAPT Regime
MATRIX
Ø 8404 Patients with ACS & PCI
Ø Randomized to radial vs femoral access
Ø Co-primary endpoints @ 30 days:
- MACE (Death, MI or stroke)
- NACE (MACE + Major Bleeding)

All Cause Mortality BARC 3-5 Bleeding Events

Bleeding Avoidance Strategies

1. Vascular Access
2. Choice of Stent
3. DAPT Regime
Major bleeding in PCI DAPT trials
(first 12 months on DAPT after PCI)

% LEADERS FREE BARC 3-5

ARCTIC STEEPLE major
DAPT DES GUSTO moderate or severe
EXCELLENT TIMI major
RESET TIMI major
OPTIMIZE trial specific
Bleeding Avoidance Strategies

1. Vascular Access
2. Choice of Stent
3. DAPT Medication
Optimal DAPT duration after coronary
stenting?

«For every complex problem there is an answer that is clear,

simple and wrong»
H.L.Menken
High Bleeding Risk Patients (HBR)

 Mostly excluded from device and APT trials

 Never specifically studied
 Current guideline recommendations: ≈20%

 BMS + one month DAPT

 DES + “shortened” DAPT
Detailed medical history?
Lab values?
There now is a choice…

PCI candidate

not HBR HBR

DES & guidelines DCS & short DAPT

 BioFreedom™ Drug Coated Stent
Selectively micro-structured surface
holds drug in abluminal surface
structures

Proprietary Highly Lipophilic Limus drug

1 1
Potential advantage
o Avoid long term late adverse effects that
might be attributable to the polymer
o Improved surface integrity since there is
no polymer to be sheared or peeled away
from the stent struts
o Possible shorter need of dual antiplatelet
therapy

1 Data on file at Biosensors Intl

current DAPT trend : A new polymer-
« shorter is better » free metallic stent

A forgotten patient
population
 Two-Year Outcomes of
High Bleeding Risk Patients after
Polymer-Free Drug-Coated Stents
Philip Urban, Philippe Garot, Damras Tresukosol,
Stuart J. Pocock, Ian Meredith, Alex Abizaid, Didier Carrié, Christoph
Naber, Andrés Iñiguez, Suneel Talwar,
Ian B.A. Menown, Evald H. Christensen, Samuel Copt,
John Gregson, Hans-Peter Stoll, Samantha Greene, 
and Marie-Claude Morice for the LEADERS FREE Investigators
LEADERS FREE Trial Design
Prospective, double-blind randomized (1:1) trial
2466 High bleeding risk (HBR) PCI patients

BioFreedom™ Gazelle™
DCS
vs. BMS

DAPT mandated for 1 month only, followed by long-term SAPT

• Primary safety endpoint:

Composite of cardiac death, MI, definite / probable stent thrombosis
at 1 year (non-inferiority then superiority)
• Primary efficacy endpoint:
Clinically-driven TLR at 1 year (superiority)
 Primary Endpoints at 1 Year
Efficacy (cd-TLR) Safety (cardiac death, MI, ST)

DCS BMS DCS BMS

%
12 %

Cumulative Percentage with Event

Cumulative Percentage with Event

15
9.8% 12.9%
9 12

9 9.4%
6
5.1%
6
3
3
HR 0.71, (95% CI = 0.56‒0.91)
p for superiority < 0.001 p < 0.0001 for non-inferiority
0 HR 0.50, (95% CI = 0.37‒0.69) 0 p = 0.005 for superiority

0 90 180 270 390 Days 0 90 180 270 390 Days

Urban P et al. N Engl J Med 2015;373:2038-47

Two Year Follow-up
 Enrollment and Follow-Up
2466 patients randomized

1,239 DCS 1,227 BMS

18 with no PCI 16 with no PCI

performed performed

1,221 analyzed (modified ITT) 1,211 analyzed (modified ITT)

28 (2.3%) patients 20 (1.7%) patients

withdrew before withdrew before
24-month visit or 24-month visit or
were lost to FU were lost to FU

1193 (97.7%) completed 1191 (98.3%) completed

24-month visit or died 24-month visit or died
 Antithrombotic Medication at Discharge

None of the regimens differ at p < 0.05

 Antithrombotic Medication after 1 month visit*
* at day 37

None of the regimens differ at p < 0.05

 Antithrombotic Medication at 2 years

p=0.03 *82% on OAC

 Primary Safety Endpoint
(Cardiac Death, MI, ST) at 2 year
20

15.3%

Patients with Event (%)

15 12.7%
12.6%
10

9.2%
5
HR 0.80 (95%CI 0.64-0.99)
p = 0.039
0
0 180 365 545 730 Days
Number at Risk
DCS 1221 1104 1052 1006 620
BMS 1211 1067 1010 973 587

2 year FU was obtained at 730 days + 60 days

 Components of Safety Endpoint
% (2 years)

p = 0.69 p = 0.04 p = 0.76

 Primary Efficacy Endpoint
(Clinically-Driven TLR) at 2 Years
20

Patients with Event (%)

15

12.0%
10 9.3%

6.8%
5

4.9% HR 0.54 (95%CI = 0.41-0.72)

P<0.0001
0
0 180 365 545 730 Days
Number at Risk
DCS 1221 1129 1061 1013 626
BMS 1211 1074 999 945 561

2 year FU was obtained at 730 days + 60 days

Subgroups at 2 years follow-up
Conclusions
ü At two years, the use of a BA9-DCS remained both
significantly safer and more effective than a control BMS in
HBR patients treated with a one-month only DAPT course

ü No subgroup was identified for which use of a BMS was

superior to a DCS

ü HBR patients suffer from a persistently high incidence of

bleeding and thrombotic events, both of which are
associated with a high and similar mortality over a one year
period

ü Identification of predictors of both the composite primary

safety event and major bleeding may help design future
trials of DAPT duration for HBR patients
Conclusion
The realisation that HBR patients require specific therapeutic
measures is having a major impact on PCI practice and
guidelines:
 Radial access whenever possible
 BMS no longer recommended
 Default approach: shorten DAPT to 3 months (DES)
or 1 month (DCS)
 Prescribe PPI liberally
 Every HBR patient is different (presentation, target lesion,
procedure), so remember to use your clinical judgment!
Thank You!