1. Transradial Approach for the Female Sex
Update on the Study of Access Site For Enhancement of PCI for Women Study
(SAFE-PCI for Women)
Mitchell W. Krucoff, MD, FACC
Professor, Medicine/Cardiology
Duke University Medical Center
Director, Cardiovascular Devices Unit

2. Mitchell W. Krucoff, MD Contracted Research / Grant Support:
Medtronic, Inc.
Eli Lilly and Company
Terumo Cardiovascular Systems Group
OrbusNeich Medical
Cordis Corporation
Abbott Vascular
Consulting Fees:

3. SAFE-PCI FOR WOMEN Principal Investigator: Sunil V. Rao MD
Study Chair: Mitchell W. Krucoff MD
Project Lead: William Barham RN

4. Background

5. Access sites bleeding in “real-world” PCI patients
ASA
Thienopyridines
IIbIIIa inhibitors
Anti-thrombin agents
Novel anti-thrombotic agents
5.4%
12.7%
Kinnaird et al Am J Cardio 2003

6. Kaplan Meier Curves for 30-Day Death, Stratified by Bleed Severity
Bleeding & 30 Day Mortality N=26,452 pts from PURSUIT, GUSTO IIb, PARAGON A & B
Kaplan Meier Curves for 30-Day Death, Stratified by Bleed Severity
log rank p-value for all four categories <0.0001
log-rank p-value for no bleeding vs. mild bleeding = 0.02
log-rank p-value for mild vs. moderate bleeding <0.0001
log-rank p-value for moderate vs. severe <0.001
Rao SV, et al. Am J Cardiol. 2005

7. Scores Predicting Bleeding risk in PCI
Mehran R, et. al. JACC 2010

8. Predictors of Major Femoral Bleeding N=17,901 pts from Mayo Clinic 1994-2005
Major femoral bleeding defined as hematoma > 4 cm, external bleeding requiring surgery
or blood transfusion, or retroperitoneal hematoma
Doyle BJ, et. al. JACC:Interventions 2008

9. PCI-related outcomes in women N=22,725 PCI pts in the BMC2 Registry
Risk of PCI outcomes Women vs. Men
Duvernoy CS, et. al. AHJ 2010

10. ACC-NCDR CATH-PCI Registry: USA Use of radial PCI
Radial access: 1.32%
Rao, S. V. et al. J Am Coll Cardiol Intv 2008;1:

11. Transradial access and outcomes N=21 studies, 5600 patients
1.0
Transfemoral better
Transradial better
PCI Failure
Access site crossover
Death
Death, CVA, or MI
Major bleeding
0.27 ( )
0.71 ( )
0.74 ( )
3.82 ( )
1.31 ( )
Jolly SS, AHJ 2008

14. 2006 FDA – Duke/DCRI Memorandum Of Understanding (MOU)
Cardiac Safety Research Consortium
(CSRC)
A Transparent Public-Private Partnership of Stakeholders

15. The TREAT Initiative

16. TransRadial Education, Assessment & Therapy: June 2010
Regulatory
FDA:
CDER
CDRH
OC OWH
Societies
ACC
SCAI
ESC
SOLACI
Academia
Duke
Harvard
Cleveland Clinic
Columbia
Emory
Wash Hrt Ctr
Mayo Clinic
Johns Hopkins
Industry
Abbott
Medtronic
Terumo
Cordis/J&J
The MEDCO
Eli Lilly (Daichi)
Sanofi/BMS
Federal
NIH
AHRQ

17. ACC National Cardiovascular Data Registries
National EDC infrastructure
Fully operational quality metrics (clinical enterprise)
Widely vetted data fields
Quality controls in place
Multiple procedural & therapeutic areas

18. National Cardiovascular Research Infrastructure (NCRI)
NIH/NHLBI grant (#: 1RC2HL )
PI: Robert Harrington
Duke Clinical Research Institute

19. 65% workload reduction per patient for site coordinators
EDC using NCRI* extraction from ACC-NCDR: Imbedding an RCT into Ongoing Registry
NCRI Data Interface Strategy
65% workload reduction per patient for site coordinators
Part 11 Compliant Inform Database
* Trial specific data is data that is not included in NCDR data.
*NIH/NHLBI grant (#: 1RC2HL )

20. TREAT Discussion Emphases
Prospective RCT design
Patient selection bias
Confounding adjuncts:
Anti-thrombotic therapy
Vascular closure strategies
Equipoise for randomization: female sex
higher risk for vascular and bleeding complications
Smaller, more tortuous limb vessels
higher risk for bleeding even with transradial PCI

21. SAFE-PCI for Women Trial Structure
Clinical and Data Coordinating Center - DCRI
Study chair - Mitchell W. Krucoff MD,
Principal Investigator - Sunil V. Rao MD
DCRI Project lead – Britt Barham
Sponsors
Terumo Medical, Abbott Vascular, The Medicines Company, Eli Lilly others pending approval of applications
Partners
NIH-NCRI (David Kong, Eric Peterson, Bob Harrington), ACC, FDA Office of Women’s Health, CSRC, SCAI
DSMB
Spencer King (chair), Olivier Bertrand, Alexandra Lansky, Statistician TBD

22. Objectives: TRI vs. TFA Safety of TRI PCI in women Secondary:
Procedure time, radiation dose, and contrast volume
Resource use, patient preferences, and QOL
Associations with 30-day death, vascular complications and repeat revascularization
*If funding can be obtained

23. Bleeding ARC (BARC)
Mehran R et al, Circulation. 2011;123: )

24. BARC Bleeding Type 2: Overt actionable type of bleeding Type 3
Does not meet criteria for Types 3, 4, or 5
Does require evaluation by a medical professional, require non- surgical intervention by a medical professional, lead to hospitalization or increased level of care
Type 3
3a – Overt bleeding with hgb drop 3 to < 5 g/dl, or any transfusion
3b – Overt bleeding with hgb drop ≥ 5 g/dl, tamponade, requiring surgical intervention, requiring pressors
3c – ICH or intra-ocular
Type 5: Fatal bleeding
5a – Probable fatal bleeding
5b – Definite fatal bleeding
Mehran R, et. al. Circulation in press.

25. Primary efficacy and feasibility endpoints
Efficacy – BARC Types 2, 3, and 5 bleeding or major vascular complications occurring within 72 hrs of PCI or hospital discharge, whichever comes first
Vascular complications defined as:
AV fistula
Arterial pseudoaneurysm
Arterial occlusion
Primary feasibility endpoint
Procedural failure – inability to complete the procedure from the assigned access site.
CEC adjudication of Bleeding and vascular complication endpoints
Requiring surgical intervention

26. Sample size assumptions and calculations
Rate of primary composite endpoint in femoral arm – 8.0%
Assume 50% reduction with radial approach
Sample size:
1800 patients provides >90% power at 2-sided alpha=0.05

27. Inclusion/exclusion criteria
Age > 18 years
Female patient undergoing elective or urgent PCI or
Undergoing diagnostic angiography to evaluate ischemic symptoms with the possibility of PCI
Have capacity to sign informed consent
Non-palpable radial or femoral pulses
Bilateral IMA grafts
Bilateral abnormal Barbeau tests
Hemodialysis AV fistula or graft in arm to be used for PCI
INR ≥ 1.5
Planned staged PCI within 30d of index PCI
Valvular heart disease requiring surgery
Planned RHC
Primary PCI for STEMI

28. Study of Access site For Enhancing PCI for Women (SAFE-PCI for Women)*
Female patient undergoing urgent or elective PCI
Best background medical therapy
Bivalirudin, Clopidogrel, Prasugrel
2b3a at investigator’s discretion
N=1800 pts, 30 sites
Sites from NCRI
Patent hemostasis required
Vascular closure devices allowed
Radial
Femoral
Primary Efficacy Endpoint: BARC Types 2, 3, or 5 bleeding or Vascular Complications requiring surgical intervention
Primary Feasibility Endpoint: Procedural failure
Secondary endpoints: Procedure duration, total radiation dose, total contrast volume
*Planned in collaboration with ACC, CSRC, FDA Office of Women’s Health

29. Site & Enrollment Update
Active Sites: 22
Enrolling Sites: 17
Patients Randomized: 153
Patients Randomized with PCI: 49 (32%)
Target Enrollment: women undergoing PCI

30. SAFE PCI for Women: Conclusions
Female sex is associated with more bleeding and vascular complications with PCI
Trans-radial PCI has potential but unproven benefits for women
The SAFE-PCI for Women Study:
Addresses an important public health issue with a prospective multicenter RCT
Involves a unique collaboration across industry, federal agencies and professional societies
Utilizes a uniquely efficient EDC strategy through combined NCDR-NCRI processes

31. Transradial Approach for the Female Sex
Update on the Study of Access Site For Enhancement of PCI for Women Study
(SAFE-PCI for Women)
Mitchell W. Krucoff, MD, FACC
Professor, Medicine/Cardiology
Duke University Medical Center
Director, Cardiovascular Devices Unit