A randomized comparison of RadIal Vs. femorAL access for coronary intervention in ACS (RIVAL)

1. A randomized comparison of RadIal Vs. femorAL access for coronary intervention in ACS (RIVAL) SS Jolly, S Yusuf, J Cairns, K Niemela, D Xavier, P Widimsky, A Budaj, M Niemela, V Valentin, BS Lewis, A Avezum, PG Steg, SV Rao, P Gao, R Afzal, CD Joyner, S Chrolavicius, SR Mehta on behalf of the RIVAL Steering committee

2. Disclosures Funded by: • Sanofi-Aventis and Bristol-Myers Squibb (through CURRENT) • Population Health Research Institute • Canadian Network and Centre for Trials Internationally (CANNeCTIN, an initiative of Canadian Institutes of Health Research)

3. Bleeding is associated with Death and Ischemic Events HR 5.37 (3.97-7.26) HR 4.44 (3.16-6.24) HR 6.46 (3.54-11.79) Eikelboom JW et al. Circulation 2006;114(8):774-82.

4. Prior Meta-analysis of 23 RCTs of Radial vs. Femoral (N=7030) Major bleeding 0.27 (0.16-0.45) Death 0.74 (0.42-1.30) Death, MI or stroke 0.71 (0.49-1.01) PCI Procedure Failure 1.31 (0.87-1.96) Transradial better 1.0 Transfemoral better Jolly SS, et al. Am Heart J 2009;157:132-40.

5. RIVAL Study Objective - To determine if Radial vs. Femoral access for coronary angiography/PCI can reduce the composite of death, MI, stroke or non-CABG major bleeding in ACS patients

6. RIVAL Study Design 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) 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.

7. Study Outcome Definitions

8. Final Recruitment RIVAL sub-study during OASIS 7/CURRENT N= 3831 RIVAL Stand-Alone After CURRENT N= 3190 + RIVAL Total N=7,021 Follow-up complete in 99.9% CURRENT-OASIS 7. N Engl J Med. 2010;363:930-42. Mehta SR, et al. Lancet. 2010; 376:1233-43.

9. Participating Countries North America 1614 Europe 3564 Asia 1117 Middle East/Israel 239 South America 423 Australia and New Zealand 64

10. Baseline Characteristics

11. Therapies - Initial Hospitalization

12. Operator VolumeProcedure Characteristics • Vascular closure devices used in 26% of Femoral group

13. Primary and Secondary Outcomes

14. Other Outcomes * Post Hoc analysis

15. Other Outcomes * Post Hoc analysis

16. Other Outcomes

17. Access Site Major Bleeds HR 0.50 (95% CI 0.19-1.33) * *All access site major bleeds actually occurred at femoral arterial site (in radial group due to cross-over or IABP)

18. R I V A L Subgroups: Primary Outcome Death, MI, Stroke or non-CABG major Bleed Overall p-value Interaction Age <75 ≥75 0.79 Gender Female Male 0.36 BMI <25 25-35 >35 0.83 Radial PCI Volume/year by Operator ≤70 70-142.5 >142.5 0.54 Radial PCI Volume by Centre Lowest Tertile Middle Tertile 0.021 Highest Tertile Clinical Diagnosis NSTE-ACS 0.025 STEMI Radial better Femoral better 0.25 1.00 4.00 Hazard Ratio(95% CI)

19. R I V A L Results stratified by High*, Medium* and Low* Volume radial Centres *High (>146 radial PCI/year/ median operator at centre), Medium (61-146), Low (≤60) p-value Tertiles of Radial PCI Centre Volume/yr HR (95% CI) Interaction Primary Outcome High 0.021 Medium Low Death, MI or stroke 0.013 High Medium Low Non CABG Major Bleed High Medium 0.538 Low Major Vascular Complications 0.019 High Medium Low Access site Cross-over 0.003 High 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)

20. R I V A L Outcomes stratified by STEMI vs. NSTEACS % % Interaction 2N Radial Femoral p-value Primary Outcome NSTE/ACS 5063 3.8 3.5 0.025 STEMI 1958 3.1 5.2 Death, MI or stroke NSTE/ACS 5063 3.4 2.7 0.011 STEMI 1958 2.7 4.6 Death NSTE/ACS 5063 1.2 0.8 0.001 STEMI 1958 1.3 3.2 Non CABG Major Bleed NSTE/ACS 5063 0.6 1.0 0.56 STEMI 1958 0.8 0.9 Major Vascular Complications NSTE/ACS 5063 1.4 3.8 0.89 STEMI 1958 1.3 3.5 0.25 1.00 4.00 Radial better Femoral better Hazard Ratio(95% CI)

21. Updated Meta-analysis of RCTs Heterogeneity Radial(%) Femoral(%) p-value P-value Non-CABG Major Bleeds Pre-RIVAL 0.2 1.2 RIVAL 0.7 0.9 0.40 0.002 Combined 0.5 1.0 Major Vascular Access Complication Pre-RIVAL 0.6 2.5 RIVAL 1.4 3.7 0.41 <0.0001 Combined 1.0 3.1 Death,MI or Stroke Pre-RIVAL 2.3 3.3 RIVAL 3.2 3.2 0.72 0.17 Combined 2.8 3.3 Death, MI or Stroke (Radial Experts) Pre-RIVAL (Radial Expert Centre trials)* 2.8 4.1 RIVAL(highest radial PCI centre tertile) 1.3 2.7 0.67 0.005 Combined 2.3 3.5 0.25 1.00 4.00 *Radial Expert Centres defined as centres default approach radial or known expert radial centre Radial better Femoral better Hazard Ratio(95% CI)

22. Conclusion • No significant difference in primary outcome of death, MI, stroke or non-CABG major bleeding • Rates of Primary outcome appeared to be lower in Radial group in high volume radial centres and STEMI • Radial had fewer major vascular complications but similar PCI success

23. Implications • Both radial and femoral approaches are safe and effective • The reduction in vascular complications may be a reason to use radial • With increasing experience the radial approach may be associated with better outcomes

24. Acknowledgements RIVAL Program Investigators from 158 sites in 32 countries