SAFE-PCI for Women Hypotheses and Design

Determining bleeding risk

Mehran R, et. al. JACC 2010

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

Bleeding & Outcomes N=26,452 pts from PURSUIT, GUSTO IIb, PARAGON A & B

Rao SV, et al. Am J Cardiol. 2005

Kaplan Meier Curves for 30-Day Death, Stratified by Bleed Severity

PCI-related complications and costs N=335,477 Medicare pts undergoing PCI in 2002

Kugelmass A, et. al. AJC 2006

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 (0.16-0.45)

0.71 (0.49-1.01)

0.74 (0.42-1.30)

3.82 (2.83-5.15)

1.31 (0.87-1.96)

Jolly SS, AHJ 2008

Female gender and access site complications

Ahmed B, et. al. Circulation 2009

Predictors of Major Femoral Bleeding N=17,901 pts from Mayo Clinic 1994-2005

Doyle BJ, et. al. JACC:Interventions 2008

Major femoral bleeding defined as hematoma > 4 cm, external bleeding requiring surgery

or blood transfusion, or retroperitoneal hematoma

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

Rao, S. V. et al. J Am Coll Cardiol Intv 2008;1:379-386

CATH-PCI Registry: Trend in the Use of radial PCI Over Time in Key Subgroups

n=593,094

Radial access: 1.32%

Transradial PCI in women

Smaller diameter arteries

May not accommodate 6F systems readily

May be associated with greater degree of spasm

Female sex independently associated with forearm hematomas in the EASY trial

Saito S, et. al. CCI 1999

Bertrand OF, et. al. AHJ 2009

SAFE-PCI Equipoise

Females at higher risk for vascular and bleeding complications

It may be more difficult to complete transradial procedures in women

Women may be at higher risk for bleeding/vascular complications after transradial PCI

Objectives

To determine the efficacy and safety of the transradial approach to PCI in women

Secondary:

To determine the association between transradial PCI and procedure time, radiation dose, and contrast volume

To determine the association between transradial PCI and resource use, patient preferences, and quality of life*

To determine the association between transradial PCI and 30-day death, vascular complications and repeat revascularization

Inclusion/exclusion criteria

Inclusion

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

Exclusion

Non-palpable radial or femoral pulses

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

Primary efficacy and feasibility endpoints

Efficacy – BARC Types 2, 3, and 5 bleeding or majoe 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 primary endpoints

Requiring surgical intervention

Study Treatments

Radial access

Counterpuncture or anterior wall access

Either side may be used; if one side fails, then other side is recommended provided Barbeau test is ok on that side

Femoral access

Femoral head fluoroscopy or U/S guided recommended

Anticoagulation during diagnostic angiography

Radial – minimum of 40 IU/kg UFH recommended

Femoral – left to investigator discretion

Antithrombotic therapy during PCI

Bivalirudin recommended

Oral antiplatelet therapy and GPI at investigator discretion

Prasugrel recommended for patients meeting labeled criteria

Intent to use GPI must be declared prior to randomization

Study Treatments

Vascular access site hemostasis

Radial – patent hemostasis mandated

Femoral - ≥ 2 hours after bivalirudin gtt discontinued, ACT < 150 (UFH), 6 hours after last SC enox

Vascular closure devices allowed

Manual pressure and ambulation

Per local practice

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

Radial Femoral

N=2000 pts, 30 sites

Sites from NCRI

Patent hemostasis required

Vascular closure devices allowed

Primary endpoint: Composite of Procedure Failure or Vascular Complications

Secondary endpoints: Procedure duration, total radiation dose, total contrast volume

*Planned in collaboration with ACC, CSRC, FDA Office of Women’s Health