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
2006114(8)774-82.
4
Prior Meta-analysis of 23 RCTs of Radial vs.
Femoral (N7030)
Jolly SS, et al. Am Heart J 2009157132-40.
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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

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RIVAL Study Design
NSTE-ACS and STEMI (n7021)

• Key Inclusion
• Intact dual circulation of hand required
• Interventionalist experienced with both (minimum
  50 radial procedures in last year)

Randomization
Radial Access (n3507)
Femoral Access (n3514)
Primary Outcome Death, MI, stroke or
non-CABG-related Major Bleeding at 30 days
Jolly SS et al. Am Heart J. 2011161254-60.
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Study Outcome Definitions
Major Bleeding (CURRENT/ OASIS 7) Fatal gt 2 units of Blood transfusion Hypotension requiring inotropes 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
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Final Recruitment
RIVAL Stand-Alone After CURRENT N 3190
RIVAL sub-study during OASIS 7/CURRENT N 3831

RIVAL Total N7,021
Follow-up complete in 99.9
CURRENT-OASIS 7. N Engl J Med. 2010363930-42. Me
hta SR, et al. Lancet. 2010 3761233-43.
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Participating Countries
North America 1614
Europe 3564
Asia 1117
Middle East/Israel 239
South America 423

Australia and New Zealand 64
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Baseline Characteristics
Radial (n 3507) Femoral (n 3514)
Mean Age (years) 62 62
Male () 74.1 72.9
Diabetes () 22.3 20.5
Diagnosis at presentation Diagnosis at presentation Diagnosis at presentation
UA () 44.3 45.7
NSTEMI () 28.5 25.8
STEMI () 27.2 28.5
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Therapies - Initial Hospitalization
Radial(n3507) Femoral (n3514)
ASA 99.2 99.3
Clopidogrel 96.0 95.6
LMWH 51.5 51.8
UFH 33.3 31.6
Fondaparinux 10.9 10.8
Bivalirudin 2.2 3.1
GP IIb IIIa inhibitors 25.3 24.0
PCI 65.9 66.8
CABG 8.8 8.3
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Operator VolumeProcedure Characteristics
Radial (n3507) Femoral (n3514) HR (95 CI) Pvalue
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

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Primary and Secondary Outcomes
Radial(n3507) Femoral (n3514) HR 95 CI P
Primary Outcome Primary Outcome Primary Outcome Primary Outcome Primary Outcome Primary Outcome
Death, MI, Stroke, Non-CABG Major Bleed 3.7 4.0 0.92 0.72-1.17 0.50
Secondary Outcomes Secondary Outcomes Secondary Outcomes Secondary Outcomes Secondary Outcomes Secondary Outcomes
Death, MI, Stroke 3.2 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
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Other Outcomes
Radial(n3507) Femoral (n3514) HR 95 CI P
Death 1.3 1.5 0.86 0.58-1.29 0.47
MI 1.7 1.9 0.92 0.65-1.31 0.65
Stroke 0.6 0.4 1.43 0.72-2.83 0.30
Stent Thrombosis 0.7 1.2 0.63 0.34-1.17 0.14
Post Hoc analysis
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Other Outcomes
Radial(n3507) Femoral (n3514) HR 95 CI P
Major Vascular Access Site Complications 1.4 3.7 0.37 0.27-0.52 lt0.0001
TIMI Non-CABG Major Bleeding 0.5 0.5 1.00 0.53-1.89 1.00
ACUITY Non-CABG Major Bleeding 1.9 4.5 0.43 0.32-0.57 lt0.0001
Post Hoc analysis
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Other Outcomes
Radial(n3507) Femoral (n3514) P
Access site Cross-over () 7.6 2.0 lt0.0001
PCI Procedure duration (min) 35 34 0.62
Fluoroscopy time (min) 9.3 8.0 lt0.0001
Persistent pain at access site gt2 weeks () 2.6 3.1 0.22
Patient prefers assigned access site for next procedure () 90 49 lt0.0001
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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)
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R I V A L
Subgroups Primary Outcome
Death, MI, Stroke or non-CABG major Bleed
Overall
p-value
Interaction
Age
lt75
75
0.79
Gender
Female
Male
0.36
BMI
lt25
25-35
gt35
0.83
Radial PCI Volume/year by Operator
70
70-142.5
gt142.5
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)
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R I V A L
Results stratified by High, Medium and
Low Volume radial Centres
High (gt146 radial PCI/year/ median operator at
centre), Medium (61-146), Low (60)
p-value
HR (95 CI)
Tertiles of Radial PCI Centre Volume/yr
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
3.5
3.8
0.025
STEMI
1958
5.2
3.1
Death, MI or stroke
NSTE/ACS
5063
2.7
3.4
0.011
STEMI
1958
4.6
2.7
Death
NSTE/ACS
5063
0.8
1.2
0.001
STEMI
1958
3.2
1.3
Non CABG Major Bleed
NSTE/ACS
5063
1.0
0.6
0.56
STEMI
1958
0.9
0.8
Major Vascular Complications
NSTE/ACS
5063
3.8
1.4
0.89
STEMI
1958
3.5
1.3
0.25
1.00
4.00
Radial better Femoral better
Hazard Ratio(95 CI)
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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
lt0.0001
Combined
1.0
3.1
Death,MI or Stroke
Pre-RIVAL
2.3
3.3
RIVAL
3.2
3.2
Combined
2.8
3.3
0.72
0.17
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)
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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

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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

Steering Committee Steering Committee
S.S. Jolly (PI) S.R. Mehta (PI)
S. Yusuf (Chair) C.D. Joyner (Adjudication Chair)
S. Chrolavicius M. Keltai
A. Avezum F. Lanas
A. Budaj B. Lewis
J. Cairns K. Niemela
R. Diaz S.V. Rao
V. Dzavik P. G. Steg
M.G. Franzosi V. Valentin
C. B. Granger P. Widimsky
D. Xavier
DMC DMC
P. Sleight (Chair)) D. R. Holmes Jr.
J.L. Anderson D.E. Johnstone
D. DeMets
J. Hirsh
Project Office
Study Team
S. Chrolavicius (Project Manager)
B. Jedrzejowski (Research Coordinator)
M. Lawrence (Events Adjudication Coordinator)
R. Manojlovic, L. Mastrangelo, E. Pasadyn, C. Agrippa, M. McClelland, (former ) C. Cramp, C. Horsman, A. Robinson, L. Blake, W. Chen, S. Diodato, A. Lehmann, T. Sovereign, L.Wasala

Statisticians and Biometrics
R. Afzal (IDMC-Associated)
P. Gao
L. Xu
X. Yang
E. Dai