Transcript The Detrimental Impact of Chronic Renal Insufficiency

DESERT
(Drug-Eluting Stent Event
Registry of Thrombosis)
The International FDA approved
DES Thrombosis Registry
Ron Waksman, MD and Martin Leon, MD
On Behalf of the DESERT Investigators
Disclosure Statement of Financial Interest
Within the past 12 months, I or my spouse/partner have had a financial
interest/arrangement or affiliation with the organization(s) listed below.
Affiliation/Financial Relationship
• Grant/Research Support
•
Consulting Fees/Honoraria
Company
• Volcano
• Medtronic Vascular
• Abbott Vascular
• Boston Scientific
• Biotronik
• Medtronic
• Abbott Vascular
• Boston Scientific
• Lilly Daiichi
• Astra Zeneca
This is an investigator initiated trial sponsored in part by
Medtronic Vascular
Background
DES Thrombosis
• Acute and subacute DES thrombosis
are the most devastating complication
of coronary stent implantation
• Late DES thrombosis is a relatively
new and poorly studied phenomenon
• Cohort-based analyses require years
of follow-up, and very large numbers
of patients
Background
Limitations of Prior Analyses
• Most have not included angiographic and
procedural data
• Limited number of stent thrombosis events
(frequency of 2% or less):

Ability to assess only very strong correlates

Wide confidence intervals around risk estimates

A study of 5000 patients would only have
approximately 100 events, with ability to reliably
assess 5-10 predictors
DESERT: Study Objectives
• To describe the correlates (clinical, procedural,
and angiographic) of late (FDA approved) DES
thrombosis (>30 days from stent implantation)
using an adequately sized and powered casecontrol study design

500 total late Stent thrombosis events
• To describe the outcomes of patients with
stent thrombosis in the DES era
DESERT Investigator Sponsored Study
Organization
Study Role
Name
Principal Investigators
Ron Waksman, MD & Martin Leon, MD
Executive Committee
Ron Waksman, MD
Jeffrey Popma, MD
David Cohen, MD
Renu Virmani, MD
Study Management/ CRO
Project Management
Cardiovascular Research Institute
Aisha Wellington
Rebecca Torguson, MPH
Data Coordinating Center
Cardiovascular Research Institute
Kimberly Kaneshige
Zhenyi Xue, MS
Anne Hassell
Martin Leon, MD
Ajay Kirtane, MD
Alan Yeung, MD
Donald Cutlip, MD
Core Angiographic Laboratory Cardiovascular Research Foundation
DESERT Study Investigative Sites
Site Name
City, State
Country
Principal
Investigators
# Enrolled
Pairs
Washington Hospital Center
Washington, DC USA
William Suddath, MD
87
Maine Medical Center
Portland, ME USA
Thomas Ryan, MD
81
Bern University Hospital
Bern, Switzerland
Lorenz Räber, MD
64
Wake Forest University Baptist Medical Center
Winston-Salem, NC USA
Robert Applegate, MD
50
Lahey Clinic
Burlington, MA USA
Sergio Waxman, MD
36
Saint Luke’s Hospital
Kansas City, MO USA
David Cohen, MD
20
Winchester Medical Center
Winchester, VA USA
Jason Call, MD
18
Prairie Education and Research Cooperative
Springfield, IL USA
Greg Mishkel, MD
18
Miriam Hospital
Providence, RI USA
Paul Gordon, MD
20
Washington Adventist Hospital
Takoma Park, MD USA
David Brill, MD
17
Mercy General Hospital
Sacramento, CA USA
Walt Marquardt, MD
16
Columbia University Medical Center
New York, NY USA
Ajay Kirtane, MD
11
Beth Israel Deaconess Medical Center
Boston, MA USA
Don Cutlip, MD
9
Geisinger Medical Center
Danville, PA USA
Thomas Scott, DO
8
Institut Universitaire de Cardiologie
Quebec, Canada
Olivier Bertrand, MD
7
Summa Health System
Akron, OH USA
Ken Berkovitz, MD
3
New York Methodist Hospital
Brooklyn, NY USA
Sorin Brener, MD
2
Providence
Columbia, SC USA
Patrick Hall, MD
4
The Valley Hospital
Ridgewood, NJ USA
Janet Strain, MD
1
San Raffaele Hospital
Milan, Italy
Antonio Colombo, MD
6
Case Inclusion Criteria:
 Subject >18 yo
 Definite late/very late ST per ARC
definition
 Implanted with DES since 4/2003
Trial Design
Consecutive prospective enrollment
Multicenter Case-Control 1:1 Study
Limited Matching
for the Site and
± 3 days to
thrombosis event
Case
DES Implant(s)
ST Event
DES Implant(s)
> 30 days from
implant; no acute
or subacute
thombosis
Follow-Up
- 30 days
Control
Subset of Pts
Control Inclusion Criteria:
 Subject >18 yo
 No known ST per ARC definition
 Implanted with DES since 4/2003
- 180 days
- 365 days
Data Lock 26 OCT 2011
NCT00812552
DES Implant Baseline Demographics
Case
n=478
Control
n=478
P value
58.0 ± 12.6
63.3 ± 11.4
<0.001
Gender (Male)
77.4%
73.2%
0.134
Race (Black)
9.8%
6.3%
0.044
Diabetes
25.3%
29.1%
0.184
Hypertension
65.8%
73.1%
0.014
Current smokers
46.0%
27.3%
<0.001
Prior CVA or TIA
7.1%
9.1%
0.280
History of PVD
9.3%
9.9%
0.733
History of CRI
6.1%
7.2%
0.503
Dialysis
1.5%
1.5%
0.994
History of CHF
6.3%
4.6%
0.257
1.3%
1.7%
0.590
Prior CABG
11.5%
12.4%
0.690
Prior PCI
34.8%
25.8%
0.002
Prior MI
28.8%
20.6%
0.003
Prior ST (any)
2.1%
--
--
Age (Years)
Current Class (III/IV)
DES Implantation Clinical Presentation
Case
n=478
Control
n=478
P value
STEMI
20.1%
14.0%
0.013
ACS/NSTEMI
25.8%
21.0%
0.078
Unstable angina
30.4%
32.3%
0.530
Stable Angina
14.9%
18.2%
0.163
Positive functional test
15.9%
19.3%
0.174
0%
1.0%
0.062
Staged PCI
1.5%
0.6%
0.224
Other Clinical Presentation
4.6%
7.3%
0.076
1 Vessel Disease
39.2%
51.2%
0.001
2 Vessel Disease
35.0%
28.1%
3 Vessel Disease
25.8%
20.8%
28.8 ± 5.9
29.6 ± 6.4
0.029
51 ± 12
54 ± 11
<0.001
Cardiogenic Shock
Number of diseased vessels
BMI
LV EF %
DES Implantation Lesion Characteristics
Case
Lesion n=515
Control
Lesion n=625
P value
LM
0.4%
1.1%
0.196
RCA
35.0%
35.7%
0.798
LAD
42.7%
37.0%
0.048
LCX
17.7%
25.0%
0.003
SVG
4.1%
1.1%
0.001
0%
0.2%
1
Ostial
5.0%
3.7%
0.257
Proximal
42.5%
39.5%
0.304
Bifurcation
9.1%
7.1%
0.198
A
11.5%
18.5%
<0.001
B1/B2
45.1%
54.2%
C
43.5%
27.3%
Arterial Graft
Lesion Location
Lesion Classification (Visual)
DES Implantation Characteristics
Continued
Case
Lesion n=515
Control
Lesion n=625
P value
Pre DS visual (%)
87.0 ± 11.4
85.5 ± 11.2
0.034
Lesion Length visual (mm)
20.7 ± 12.7
17.0 ± 10.2
<0.001
RVD visual (mm)
3.0 ± 0.4
3.0 ± 0.5
0.255
Visual Thrombus
20.8%
13.9%
0.002
III
66.3%
80.4%
<0.001
II
13.3%
9.2%
I
3.9%
2.4%
0
16.6%
8.1%
10.7%
4.6%
<0.001
4.5%
1.4%
0.002
CTO
2.9%
2.6%
0.719
Moderate/Severe Calcium (visual)
16.0%
13.4%
0.208
Pre TIMI Flow
ISR (any)
DES ISR
Stent Details
Case
Lesion n=515
Control
Lesion n=625
P value
Cypher
50.8%
49.6%
0.688
Taxus
42.6%
40.6%
0.489
Endeavor
2.2%
1.5%
0.394
Xience/Promus
5.0%
7.0%
0.160
0
0.7%
0.130
2.9 ± 0.4
3.0 ± 0.4
0.006
DES total stented length
27.7 ± 16.5
23.2 ± 12.8
<0.001
Max deployment pressure
(atm)
14.1 ± 3.1
14.0 ± 3.1
0.364
Stents per lesion
1.3 ± 0.6
1.2 ± 0.5
0.002
37.5%
23.9%
<0.001
Other
DES diameter
Overlapping
Time to ST Event Presentation
1 year
75% of ST after 1 yr
Days to ST
Case
n=478
895 ± 651
> 30 days, < 180 days
14.3%
> 180 days, < 365 days
10.5%
> 365 days, < 730 days
23.9%
> 730 days, < 1095 days
16.4%
> 1095 days
35.0%
ST Event Clinical Presentation
Case
n=478
STEMI
66.9%
ACS/NSTEMI
22.0%
Unstable angina
7.7%
Stable Angina
1.7%
Positive functional test
1.7%
Cardiogenic Shock
4.8%
Other Clinical Presentation
1.9%
ST identified by autopsy
0.2%
LV EF %
51 ± 12
Length of Hospitalization (days)
4.3 ± 4.6
ICU stay required
Length of ICU Stay (days)
72.6%
2.5 ± 3.5
ST Event: Antiplatelet Therapy Intake
Case
n=478
DES Implant
Not Taking
Taking at ST
Discharge
at ST
If not,
stopped
within 5
days of ST
Unknown at
ST
Aspirin
99.4%
74.6%
24.8%
67.5%
3.8%
Clopidogrel
98.5%
31.8%
66.0%
51.8%
4.6%
Ticlopidine
1.3%
0.4%
1.3%
66.7%
1.0%
Prasugrel
0.4%
0.4%
0
--
--
DAPT
99.4%
29.8%
64.9%
43.9%
3.8%
ST Event Lesion Characteristics
Case
Lesion n=514
Visual Thrombus
99.6%
Pre DS visual (%)
96.5 ± 10.5
Pre TIMI Flow
III
10.9%
II
10.9%
I
3.8%
0
74.5%
Malapposition
By IVUS (Investigator determination)
4.9%
By Angiography (Investigator determination)
5.8%
Revascularization any
96.3%
CABG
1.0%
PCI
95.3%
ST Lesion PCI Details
Case
Lesion n=490
Balloon
77.6%
Thrombectomy
46.1%
Cutting Balloon
0.6%
Laser
2.0%
Atherectomy
1.4%
Re-Drug Eluting Stent
30.6%
Bare Metal Stent
20.2%
Perfusion Catheter, Anticoagulant
0.8%
Perfusion Catheter, Other Drug
Other, PCI Device
0%
1.0%
Post TIMI Flow
III
93.4%
II
3.7%
I
0.8%
0
2.1%
No Reflow/Abrupt Closure
1.8%
ST Events In Hospital
Available Follow up Post Discharge
from ST event to 12 months
%
Available Follow up Post Discharge
from ST event MACE KM Curve
At Risk
170
158
153
149
140
135
128
119
116
111
108
102
86
Correlates of Late DES Stent
Thrombosis
p value
0.095
0.079
0.080
0.093
0.068
<0.001
<0.001
0.010
0.035
0.040
0.047
Independent Correlates of Late
DES Stent Thrombosis
p value
<0.001
<0.001
0.010
0.035
0.040
0.047
Limitations
• Prevalence of Late and Very Late DES
ST cannot be assessed
• In DESERT 90% of the patients in both
groups had first generation DES
• This analysis only identifies patients
who survived the acute event of ST and
presented for an angiogram
• Angiographic data is currently being
analyzed
Summary
• DESERT is the largest case-control registry of
late and very late DES Stent Thrombosis
• In DESERT, the majority of the Late ST
occurred after one year (~75%) and continued
to occur up to 7.3 years
• The clinical presentation of late ST was mainly
MI (66.9% STEMI and 22% NSTEMI)
• Nearly 30% of the patients with L ate ST were
on DAPT at the time of the event
• In hospital mortality of patients who presented
with late ST was 3.8% and 1.67% at one year
Conclusions

Patients who had first generation DES continue to
be at risk for late stent thrombosis up to 7 years

Younger patients, smokers, black ethnicity,
patients with multi vessel disease, STEMI, or SVG
lesions are at higher risk of developing late ST and
should be reconsider for DES, or for a potent or
longer DAPT regimen

Mortality with late ST is lower when compared with
historically reported acute and subacute ST. This
suggest a different pathological mechanism for late
ST: (late restenosis and/or neo-atherosclerosis)
Thank You for your attention