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