1. The PLATINUM DIVERSITY Study Everolimus-eluting Stent Implantation
Outcomes in Women and Minorities Compared with White Men One Year After
Everolimus-eluting Stent Implantation
Good morning. On behalf of the PLATINUM DIVERSITY investigators, it is my pleasure and honor to present the initial results of the PLATINUM DIVERSITY study.
Wayne Batchelor, M.D. and Roxana Mehran, M.D.
on behalf of the PLATINUM DIVERSITY investigators

2. Financial Disclosures
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
Company
Grant/Research Support
Consulting Fees/Honoraria
Boston Scientific
Abbott, Medtronic

3. Diversity in the U.S. Population
Minorities expected to represent over half (52%) of the U.S. population by 2050
NOTE: Hispanics may be of any race
U.S. Census Bureau, 2009 National Projections supplement to the 2008 National Projections, August 14, 2008

4. Disparities in Clinical Practice and Research
Whites account for 64% of population but 85-90% of PCI volume
and clinical trial enrollment
US Population 2010*
BSC ION, Libertē and PE Plus Studies**: Pooled Patient Demographics
Composition(%)
Registry US
0.6 6
0.1
0.2
0.3
0.9
0.4 5
2.5 16
5.0 13 87 72
US PCI Procedures 2012*
The data garnered from clinical research trials form the basis for evaluating the safety and efficacy of medical devices. However, despite major efforts from the US FDA and NIH, enrollment of women and minorities in cardiovascular clinical trials remains poor.
N=7987
*MedPar 2012, 2013 Master Hospital file & US 2010 Census
**Data supplied by Dr. P. Underwood, BSC

5. PURPOSE
Construct a novel study design that would specifically address the diversity gap
Determine if there are significant differences in 1 year clinical outcomes between women and minorities compared with white men in the era of second generation DES
To characterize and evaluate the impact of social/behavioral/economic determinants of health in women and minorities

6. PLATINUM DIVERSITY STUDY DESIGN
Multicenter, single-arm, prospective “enriched” cohort study
52 U.S. sites enrolling women and minorities
Pooling of data with PROMUS ELEMENT PAS f
(I) PLATINUM DIVERSITY COHORT (n=1,501)
Inclusion criteria
Patients received at least 1 Promus PREMIER stent
Self-identified as ≥1 of the following:
- Female
- Black, of African heritage
- Hispanic/Latino
- American Indian/Alaskan Native
(II) PROMUS ELEMENT PLUS PAS COHORT (n=2,687)*
prospective, open-label, multicenter, all-comers observational study designed to examine 1 yr outcomes with PROMUS Element Plus stent
*Kandzari et al Am J Cardiol. 2016

7. STUDY DESIGN: STATISTICS Minorities vs White men
1° Endpoint:
Death/MI/TVR at 12 months
Primary Analyses
Women vs White men
Minorities vs White men
Expected rates:
White men = 7.3% (n=1628 PE Plus PAS)
Women = 10.1% (pooled PE Plus PAS
(n=806) & PLATINUM Diversity)
2-sided α = 5%
Power = ~0.80
Expected attrition = 5%
n=1000 (Women in PLATINUM Diversity)
Expected rates:
White men = 7.3% (n=1628 PE Plus PAS)
Minority = 10.6 % (pooled PE Plus PAS (N=284) & PLATINUM Diversity)
2-sided α = 5%
Power = ~0.80
Expected attrition = 5%
n=700 (Minority in PLATINUM Diversity)

8. MI (STEMI and NonSTEMI) TVR Death/MI Definite/Probable ST (ARC)
SECONDARY ENDPOINTS
Death
MI (STEMI and NonSTEMI)
TVR
Death/MI
Definite/Probable ST (ARC)
Definitions for above are as reported in the following:
One-Year Outcomes in "Real-World" Patients Treated With a Thin-Strut, Platinum-Chromium, Everolimus-Eluting Stent (from the PROMUS Element Plus US Post-Approval Study [PE-Plus PAS]). Kandzari et al. Am J Cardiol. 2016

9. STUDY DESIGN Total Patients N=4,188 Platinum DIVERSITY N=1,501
PE Plus PAS
N=2,687
Women
N=1,863
White Men
N=1,635
Minority
N=1,059
12-month Follow-up
94% (N=1,755)
12-month Follow-up
95% (N=1,556)
12-month Follow-up
93% (N=982)

10. STUDY COMMITTEES Principal Investigators Roxana Mehran Wayne Batchelor
Mount Sinai Medical Center
Wayne Batchelor
Tallahassee Memorial Hospital
Joseph Kannam (chair)
Germano DiSciascio
Claude Hanet
Goran Stankovic
Boston Scientific Corporation
Lisa Currier, Project Manager
Project Management, Statistics
PRA International
Colleen Mullenix, Project Manager
Monitoring, Data Management, Safety, Statistics
Independent
Clinical Events
Committee
Study Sponsor
CRO

11. PLATINUM DIVERSITY TOP SITES
Study Principal Investigators
Roxana Mehran (81)
Mount Sinai Medical Center
Wayne Batchelor (48)
Tallahassee Memorial Hospital
Top Enrolling Centers
Principal Investigators
Scott Davis (101)
Arkansas Cardiology
Roger Hill (38)
St Bernards Heart and Vascular
Luis Tami (96)
Research Physicians Network Alliance
Steven Hearne (36)
Delmarva Heart Research Foundation
John Wang (71)
MedStar Union Memorial Hospital
Vince Vismara (35)
Palmetto Health
Islam Othman (69)
NC Heart and Vascular Research
Jerrold Grodin (34)
VA North Texas Health Care System
Osvaldo Gigliotti (65)
Seton Heart Institute
Jerome E Williams (34)
Novant Health Heart and Vascular Institute
Amir Haghighat (47)
Cardiovascular Institute of Northwest Florida
Robert Pyo (33)
Montefiore Medical Center
Sarabjeet Singh (46)
Central Cardiology Medical Clinic
Elie Gharib (32)
CAMC Clinical Trials Center
Mario Lopez (43)
Charlotte Heart and Vascular Institute
Hosbedar Tamboli (31)
Bay Area Cardiology
Gregory Giugliano (40)
Baystate Medical Center
Zafir Hawa (31)
North Kansas City Hospital
Phillip Horwitz (39)
University of Iowa Hospitals and Clinics
Tim Shapiro (30)
Lankenau Medical Center
Sandeep Nathan (38)
University of Chicago Medical Center
George Kichura (29)
St. Louis Heart and Vascular

12. 6 months ahead of schedule
STUDY ENROLLMENT
Enrollment complete
6 months ahead of schedule
1,501 Patients
at 52 sites
No.
Patients
First Patient October 2014
August 2015
Enrollment Complete
February 2016
Expected Completion

13. DEMOGRAPHICS PLATINUM Diversity N=1,501 Women Minorities N=1,057 N=766
White
Black
Hispanic
Asian
American Indian
Pacific Islander
Other
Women
N=1,057
Minorities
N=766
42%
58%

14. BASELINE CHARACTERISTICS
Variable
White Men
1,635 pt
2,207 les
Women
1,863 pt
2,463 les
P-value
Minority
1,059 pt
1,455 les
Age, y
63 ± 11
66 ± 12
<0.0001
62 ±11
0.01
Current Smoker, % 22
0.73 24
0.50
Current Diabetes, % 34 42 51
Hyperlipidemia, % 76 75
0.42 72
0.05
Hypertension, % 84
History of CAD, % 60 63
0.07 48
ACS, % 59 55 53
0.0006
MI <72h, % 31
0.02 33
0.002
Renal Disease, % 9 14 20
RVD, mm
3.0 ± 0.54
2.9 ± 0.50
2.9 ± 0.52
0.003
Lesion Length, mm
17 ± 11
18 ± 11
0.65
19 ± 11
Severe Calcification, %
3.3
8.8
9.3
Thrombus, % 13
9.1
8.6
Study Stents/pt
1.5 ± 0.82
1.5 ± 0.77
0.37
1.6 ± 0.87
0.11
White men from PE Plus PAS; Females/minorities from DIVERSITY and PE Plus PAS ;
P-value from χ2 test; les=lesions

15. ANTIPLATELET MEDICATION USE
100 90 80 70
ASA
White men
Women
Minority
P-value (vs white men)
100 90 80 70
Dual Antiplatelet Therapy
P-value (vs white men)
(Discharge)
Time (Months)
Patients were treated with one of the following P2Y12 inhibitors per standard of care; P-value from χ2 test

16. PRIMARY ENDPOINT: DEATH/MI/TVR
White men
Women
1 Endpoint
Components of 1 Endpoint
P=0.33
P=0.04
P=0.06
P=0.27
Binary Rates; Per protocol, MI definition based on CK > 2x ULN; P-value from χ2 test

17. PRIMARY ENDPOINT: DEATH/MI/TVR
White men
Women
Minority
1 Endpoint
Components of 1 Endpoint
P=0.33
P=0.04
P=0.06
P=0.27
P=0.08
P=0.03
P=0.0002
P=0.97
Binary Rates; Per protocol, MI definition based on CK > 2x ULN; P-value from χ2 test

18. SECONDARY ENDPOINT: DEATH/MI
White men
Women
Minority 10 8 6 4 2
P-values
White men vs Women P=0.006
White men vs Minority P=0.0002
6.5
5.1
Death/MI, %
3.0
180
365
Time (Days)
At-risk Patients
White Men
1635
1569
1068
Women
1863
1795
1251
Minority
1059
1017
715
Kaplan Meier Rates; P-value from log-rank test

19. Kaplan Meier Rates; P-value from log-rank test
12 MONTH TVR
White men
Women
Minority 10 8 6 4 2
P-values
White men vs Women P=0.95
White men vs Minority P=0.91
5.9
5.6
TVR, %
4.8
180
365
Time (Days)
At-risk Patients
White Men
1635
1554
1045
Women
1863
1784
1227
Minority
1059
1011
707
Kaplan Meier Rates; P-value from log-rank test

20. Kaplan Meier Rates; P-value from log-rank test
DEFINITE/PROBABLE ST
White men
Women
Minority 10 8 6 4 2
P-values
White men vs Women P=0.31
White men vs Minority P=0.20
Definite/Probable ST, %
1.2
0.9
0.7
180
365
Time (Days)
At-risk Patients
White Men
1635
1567
1062
Women
1863
1797
1242
Minority
1059
1018
711
Kaplan Meier Rates; P-value from log-rank test

21. PRESPECIFIED MULTIVARIATE ANALYSIS
Women vs White Men
Multivariate Adjustment
Odds Ratio (95% CI)
P-value
C-statistic
Death/MI/TVR
1.1 [0.87, 1.47]
0.35
Death/MI
1.6 [1.11, 2.39]
0.01
0.74
Death
1.4 [0.91, 2.28]
0.11 MI
1.7 [0.91, 3.09]
0.09
TVR
0.87 [0.63, 1.19]
0.42
Minority vs White Men
Multivariate Adjustment
Odds Ratio (95% CI)
P-value
C-statistic
Death/MI/TVR
1.1 [0.81, 1.47]
0.57
Death/MI
1.9 [1.22, 2.80]
0.004
0.74
Death
1.0 [0.62, 1.75]
0.11 MI
2.6 [1.40, 4.82]
0.002
TVR
0.87 [0.63, 1.19]
0.95
Risk vs White Men:
Lower
Higher
Variables in the analysis include history of CABG, CHF, MI, MVD, PCI, renal disease, ISR, hypertension, PVD, CVA, LM, hyperlipidemia, AF, TIA, cardiogenic shock, NYHA Class , family history of CAD, BMI as well as diabetic, angina and smoking status; lesion/procedural characteristics: de novo lesion, calcification, CTO and TO, tortuosity, lesion within or distal to a >60 bend in the vessel, ostial or bifurcated lesion, culprit Lesion for STEMI, TIMI flow, thrombus, restenotic lesion, target lesion vessel, # study stents implanted, pre-or post-dilatation, brachytherapy, IVUS

22. CONCLUSIONS
“All-comers” coronary stent trials do not represent a random selection of U.S. patients and tend to lack adequate enrollment of women and minorities
By employing an “enriched enrollment” prospective cohort design, PLATINUM DIVERSITY efficiently produced valuable outcomes data to help bridge this gap
Despite significant differences in baseline clinical and angiographic characteristics, women, minorities and white men showed no differences in death/MI/TVR

23. CONCLUSIONS Women showed an increased risk of death/MI
Minorities showed an increased risk of MI and death/MI
Similar rates of TVR and ST among all 3 groups suggest that “device failure” is unlikely to account for the observed differences
These results highlight the heterogeneity conferred by sex and race and suggest further study into the biologic, social, behavioral, and economic factors that impact CV risk after DES

24. SOCIAL/BEHAVIORAL FACTORS
PLATINUM DIVERSITY
SOCIAL/BEHAVIORAL FACTORS
Marital Status/Living situation
Income
Employment status
Education
Hx alcohol/substance abuse
Social/
behavioral determinants of health
Life
Wellness
Access or healthcare utilization
Language
Birth country
1 language/English fluency
Language concordance
BMI
Exercise regularity
Type of insurance
Early subject contact
Current PCP
Time/distance to hospital
Smartphone usage
Parameters not collected in PE Plus PAS
Future analyses will investigate the impact of these parameters

25. ACKNOWLEDGEMENTS Paul Underwood Dominic Allocco
Peter Mauer Craig Thompson
Eileen Rose Kristine Roy
Songtao Jiang Peter Lang
Eileen Rose Alison Osattin
Peter Lam

26. End