desert ( d rug- e luting s tent e vent r egistry of t hrombosis)
DESCRIPTION
DESERT ( D rug- E luting S tent E vent R egistry of T hrombosis). The International FDA approved DES Thrombosis Registry. Ron Waksman, MD and Martin Leon, MD On Behalf of the DESERT Investigators. Grant/Research Support Consulting Fees/Honoraria. Volcano Medtronic Vascular - PowerPoint PPT PresentationTRANSCRIPT
DESERTDESERT((DDrug-rug-EEluting luting SStent tent EEvent vent RRegistry of egistry of TThrombosis)hrombosis)
The International FDA approved The International FDA approved DES Thrombosis RegistryDES Thrombosis Registry
Ron Waksman, MD and Martin Leon, MDRon Waksman, MD and Martin Leon, MDOn Behalf of the DESERT InvestigatorsOn Behalf of the DESERT Investigators
Disclosure Statement of Financial Interest
• Grant/Research Support
• Consulting Fees/Honoraria
• Volcano• Medtronic Vascular • Abbott Vascular• Boston Scientific• Biotronik• Medtronic• Abbott Vascular• Boston Scientific• Lilly Daiichi• Astra Zeneca
Within the past 12 months, I or my spouse/partner have had a financial Within the past 12 months, I or my spouse/partner have had a financial interest/arrangement or affiliation with the organization(s) listed below.interest/arrangement or affiliation with the organization(s) listed below.
Affiliation/Financial Relationship Company
This is an investigator initiated trial sponsored in part by Medtronic Vascular
• Acute and subacute DES thrombosis Acute and subacute DES thrombosis are the most devastating complication are the most devastating complication of coronary stent implantationof coronary stent implantation
• Late DES thrombosis is a relatively Late DES thrombosis is a relatively new and poorly studied phenomenonnew and poorly studied phenomenon
• Cohort-based analyses require years Cohort-based analyses require years of follow-up, and very large numbers of of follow-up, and very large numbers of patientspatients
Background
DES ThrombosisDES Thrombosis
• Most have not included angiographic and Most have not included angiographic and procedural dataprocedural data
• Limited number of stent thrombosis events Limited number of stent thrombosis events (frequency of 2% or less):(frequency of 2% or less):
Ability to assess only very strong correlatesAbility to assess only very strong correlates
Wide confidence intervals around risk estimatesWide confidence intervals around risk estimates
A study of 5000 patients would only have A study of 5000 patients would only have approximately 100 events, with ability to reliably approximately 100 events, with ability to reliably assess 5-10 predictorsassess 5-10 predictors
BackgroundLimitations of Prior AnalysesLimitations of Prior Analyses
DESERT: Study Objectives
• To describe the correlates (clinical, procedural, To describe the correlates (clinical, procedural, and angiographic) of late (FDA approved) DES and angiographic) of late (FDA approved) DES thrombosis (>30 days from stent implantation) thrombosis (>30 days from stent implantation) using an adequately sized and powered case-using an adequately sized and powered case-control study designcontrol study design
500 total late Stent thrombosis events500 total late Stent thrombosis events
• To describe the outcomes of patients with To describe the outcomes of patients with stent thrombosis in the DES erastent thrombosis in the DES era
DESERT Investigator Sponsored Study Organization
Study Role NamePrincipal Investigators Ron Waksman, MD & Martin Leon, MD
Executive Committee Ron Waksman, MD Martin Leon, MDJeffrey Popma, MD Ajay Kirtane, MDDavid Cohen, MD Alan Yeung, MDRenu Virmani, MD Donald Cutlip, MD
Study Management/ CROProject Management
Cardiovascular Research InstituteAisha WellingtonRebecca Torguson, MPH
Data Coordinating Center Cardiovascular Research InstituteKimberly KaneshigeZhenyi Xue, MSAnne Hassell
Core Angiographic Laboratory Cardiovascular Research Foundation
DESERT Study Investigative SitesSite 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
Trial Design
Case
Follow-Up
ST Event
DES Implant(s) DES Implant(s)
ControlLimited Matching for the Site and
± 3 days to thrombosis event
- 30 days- 180 days- 365 days
> 30 days from implant; no acute
or subacute thombosis
Control Inclusion Criteria: Subject >18 yo No known ST per ARC definition Implanted with DES since 4/2003
Subset of Pts
Case Inclusion Criteria: Subject >18 yo Definite late/very late ST per ARC definition Implanted with DES since 4/2003
NCT00812552Data Lock 26 OCT 2011
Multicenter Case-Control 1:1 StudyMulticenter Case-Control 1:1 Study
Consecutive prospective enrollmentConsecutive prospective enrollment
DES Implant Baseline DemographicsCasen=478
Controln=478
P value
Age (Years) 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
Current Class (III/IV) 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% -- --
DES Implantation Clinical Presentation
Casen=478
Controln=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
Cardiogenic Shock 0% 1.0% 0.062
Staged PCI 1.5% 0.6% 0.224
Other Clinical Presentation 4.6% 7.3% 0.076
Number of diseased vessels
1 Vessel Disease 39.2% 51.2% 0.001
2 Vessel Disease 35.0% 28.1%
3 Vessel Disease 25.8% 20.8%
BMI 28.8 ± 5.9 29.6 ± 6.4 0.029
LV EF % 51 ± 12 54 ± 11 <0.001
DES Implantation Lesion CharacteristicsCase
Lesion n=515Control
Lesion n=625P 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
Arterial Graft 0% 0.2% 1
Lesion Location
Ostial 5.0% 3.7% 0.257
Proximal 42.5% 39.5% 0.304
Bifurcation 9.1% 7.1% 0.198
Lesion Classification (Visual)
A 11.5% 18.5% <0.001
B1/B2 45.1% 54.2%
C 43.5% 27.3%
DES Implantation Characteristics Continued
CaseLesion n=515
ControlLesion 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
Pre TIMI Flow
III 66.3% 80.4% <0.001
II 13.3% 9.2%
I 3.9% 2.4%
0 16.6% 8.1%
ISR (any) 10.7% 4.6% <0.001
DES ISR 4.5% 1.4% 0.002
CTO 2.9% 2.6% 0.719
Moderate/Severe Calcium (visual) 16.0% 13.4% 0.208
Stent Details
CaseLesion n=515
ControlLesion 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
Other 0 0.7% 0.130
DES diameter 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
Overlapping 37.5% 23.9% <0.001
Time to ST Event Presentation
Casen=478
Days to ST 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%
1 year
75% of ST after 1 yr
ST Event Clinical Presentation
Casen=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 72.6%
Length of ICU Stay (days) 2.5 ± 3.5
ST Event: Antiplatelet Therapy Intake
Casen=478
DES Implant Discharge
Taking at STNot Taking
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
CaseLesion 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 DetailsCase
Lesion n=490Balloon 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 0%
Other, PCI Device 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
p value
0.095
0.079
0.080
0.093
0.068
<0.001
<0.001
0.010
0.035
0.040
0.047
Correlates of Late DES Stent Thrombosis
p value
<0.001
<0.001
0.010
0.035
0.040
0.047
Independent Correlates of Late DES Stent Thrombosis
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