Why Radial Access Should be the Default for Women undergoing PCI? Sanjit Jolly MD, FRCP Interventional Cardiologist, Hamilton Health Sciences, McMaster University, Hamilton, Canada

Sanjit S. Jolly, MD Grant Support or Honoraria: Medtronic, Bristol Myers Squibb, Sanofi-Aventis, GlaxoSmithKline

Female gender and access site complications Ahmed B, et. al. Circulation 2009

Radial approach in women Data from 593,000 procedures in NCDR CathPCI Femoral approach as the reference Rao SV, et. al. JACC Intv 2008

Rates of Radial Approach in Women Over Time N=2 Rates of Radial Approach in Women Over Time N=2.2 million procedures in CathPCI 2007-2011 Feldman D, et. al. AHA 2012

RIVAL Study Design Primary Outcome: Death, MI, stroke NSTE-ACS and STEMI (n=7021) Key Inclusion: Intact dual circulation of hand required Interventionalist experienced with both (minimum 50 radial procedures in last year) Randomization Radial Access (n=3507) Femoral Access (n=3514) Blinded Adjudication of Outcomes Primary Outcome: Death, MI, stroke or non-CABG-related Major Bleeding at 30 days Jolly SS et al. Am Heart J. 2011;161:254-60.

Definitions Major Bleeding (CURRENT/ OASIS 7) Fatal > 2 units of Blood transfusion Hypotension requiring inotropes Leading to hemoglobin drop of ≥ 5 g/dl Requiring surgical intervention ICH or Intraocular bleeding leading to significant vision loss Major Vascular Access Site Complications Large hematoma Pseudoaneurysm requiring closure AV fistula Other vascular surgery related to the access site

Operator Volume Procedure Characteristics Radial (n=3507) Femoral (n=3514) HR (95% CI) P value Operator Annual Volume PCI/year (median, IQR) 300 (190, 400) 300 (190,400) Percent Radial PCI (median, IQR) 40 (25,70) 40 (25, 70) PCI Success 95.4 95.2 1.01 (0.95-1.07) 0.83 Vascular closure devices used in 26% of Femoral group

Primary and Secondary Outcomes Radial (n=3507) % Femoral (n=3514) % HR 95% CI P Primary Outcome Death, MI, Stroke, Non-CABG Major Bleed 3.7 4.0 0.92 0.72-1.17 0.50 Secondary Outcomes Death, MI, Stroke 3.2 0.98 0.77-1.28 0.90 Non-CABG Major Bleeding 0.7 0.9 0.73 0.43-1.23 0.23

Other Outcomes Radial (n=3507) % Femoral (n=3514) % HR 95% CI P Major Vascular Access Site Complications 1.4 3.7 0.37 0.27-0.52 <0.0001 Other Definitions of Major Bleeding TIMI Non-CABG Major Bleeding 0.5 1.00 0.53-1.89 ACUITY Non-CABG Major Bleeding* 1.9 4.5 0.43 0.32-0.57 * Post Hoc analysis

Site of Non-CABG Major Bleeds (RIVAL definition) *Sites of Non Access site Bleed: Gastrointestinal (most common site), ICH, Pericardial Tamponade and Other

Other Outcomes Radial (n=3507) Femoral (n=3514) P Access site Cross-over (%) 7.6 2.0 <0.0001 PCI Procedure duration (min) 35 34 0.62 Fluoroscopy time (min) 9.3 8.0 Persistent pain at access site >2 weeks (%) 2.6 3.1 0.22 Patient prefers assigned access site for next procedure (%) 90 49 Symptomatic radial occlusion requiring medical attention 0.2% in radial group

Non CABG major bleeding by actual access site used to complete procedure (not intent to treat)* *Post Hoc analysis

Subgroups: Primary Outcome R I V A L Subgroups: Primary Outcome Death, MI, Stroke or non-CABG major Bleed Overall p-value Interaction Age <75 ≥75 0.786 Gender Female Male 0.356 BMI <25 25-35 0.637 >35 Radial PCI Volume by Operator ≤70 70-142.5 >142.5 0.536 Radial PCI Volume by Centre Lowest Tertile Middle Tertile Highest Tertile 0.021 Diagnosis at presentation NSTE-ACS STEMI 0.025 0.25 1.00 4.00 Radial better Femoral better Hazard Ratio (95% CI)

High*, Medium* and Low* Volume Radial Centres Results stratified by High*, Medium* and Low* Volume Radial Centres R I V A L *High (>146 radial PCI/year/ median operator at centre), Medium (61-146), Low (≤60) Tertiles of Radial PCI Centre Volume/yr HR (95% CI) p-value Primary Outcome Interaction High 0.021 Medium Low Death, MI or stroke High 0.013 Medium Low Non CABG Major Bleed High Medium 0.538 Low Major Vascular Complications Of note in high volume femoral PCI centres, femoral was not better than radial. High 0.019 Medium Low Access site Cross-over High 0.003 Medium Low No significant interaction by Femoral PCI center volume 0.25 1.00 4.00 16.00 Radial better Femoral better Hazard Ratio(95% CI)

Major Vascular Complications in RIVAL

Specific Challenges in Women for TRA Smaller radial diameter/ Higher rates of Spasm Greater Expertise needed Need proficiency with 5 Fr PCI

Implications Operators should learn and practice radial access Women at higher risk of bleeding and so should not be denied TRA

Radial Access Now Class IIa indication in ACC guidelines PCI inHosptals Without On-Sie Surgical Backup I IIa IIb III A Level of Evidence of A 2011 ACCF/AHA/SCAI Guideline for PCI. JACC. 2011; 58:e44-122. 19

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, 65 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