The TREAT Study: Can Devices Lower Bleeding Rates? Sunil V. Rao MD Assistant Professor of Medicine Duke University Medical Center Durham VA Medical Center Duke Clinical Research Institute

Sunil V. Rao, MD DISCLOSURES Consulting Fees Honoraria The Medicines Company, Bristol-Myers Squibb, Astra Zeneca Honoraria sanofi-aventis U.S. LLC Grants/Contracted Research Cordis, a Johnson & Johnson company, Momenta Pharmaceuticals, Inc., Portola Pharmaceuticals, Inc. I intend to reference unlabeled/ unapproved uses of drugs or devices in my presentation. I intend to reference Bivalirudin and Fondaparinux for ACS; Enoxaparin for PCI; Clopidogrel for stenting.

Disclosures Consultant, Speakers’ Bureau, Honoraria Sanofi-Aventis, Bristol Myers Squibb The Medicines Company Terumo Corporation Astra Zeneca Research funding Cordis Corporation Momenta Pharmaceuticals Portola Pharmaceuticals Off-label uses of drugs/devices will not be discussed

Rationale Bleeding is a common complication Bleeding is associated with short- and long-term morbidity and mortality Bleeding most commonly occurs at the vascular access site in pts undergoing PCI Bleeding limits the clinical use of certain antithrombotic therapies

Why bleeding? - In Hospital PCI Mortality & Bleeding Peterson ED ACC 2007 Mehta SR ACC 2007

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

PCI-related complications and costs N=335,477 Medicare pts undergoing PCI in 2002 Given the incidence of vascular complications and the cost per complication, this is roughly $117.6 million dollars in costs Kugelmass A, et. al. AJC 2006

Bleeding in PCI Trials: Frequency and site* Among bleeders *All transfemoral access Rao SV, et. al., JACC 2010 (in press)

Bleeding in NSTEMI Overall Among bleeders Access site bleeds are 29.8% of all bleeds Rao SV, et. al., JACC 2010 (in press)

Bleeding in STEMI Among bleeders Rao SV, et. al., JACC 2010 (in press)

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

The design The goal: Can transradial reduce bleeding with accepted/approved antithrombotics and INFORM THE LABEL? TransRadial Eduction And Therapy (TREAT) Program A series of programs that includes both prospective clinical investigations and educational programs Prospective registry Uses NCDR CathPCI as a backbone Site identification Data collection with 1-2 unique pages

Prevalence of radial approach in the US N = 593,094 PCI procedures 2004-2007 606 sites 1.3% of all PCI procedures Rao SV, et. al. JACC: CI 2008

TREAT - Challenges Low penetration of transradial in the US “E” part of the TREAT Sampling of various antithrombotic agents and class effect of radial? Does an effect in one agent translate to an effect in another in the same class? Is it reasonable to expect that data from a registry is sufficient to inform drug labeling? Some agents of interest are in the last phase of the product life cycle