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
RIVAL
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)
RIVAL
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.
RIVAL
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.
RIVAL
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
RIVAL
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.
RIVAL
Study Outcome Definitions
Major
Bleeding
(CURRENT/
OASIS 7)
• Fatal
• > 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
RIVAL
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.
RIVAL
Participating Countries
North America
1614
Europe 3564
Middle
East/Israel 239
Asia
1117
South America 423
Australia and New
Zealand 64
RIVAL
Baseline Characteristics
Radial
(n =3507)
Femoral
(n =3514)
62
62
Male (%)
74.1
72.9
Diabetes (%)
22.3
20.5
UA (%)
44.3
45.7
NSTEMI (%)
28.5
25.8
STEMI (%)
27.2
28.5
Mean Age (years)
Diagnosis at presentation
RIVAL
Therapies - Initial Hospitalization
Radial
Femoral
(n=3507)
%
(n=3514)
%
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
RIVAL
Operator Volume
Procedure Characteristics
Radial
(n=3507)
Femoral
(n=3514)
300
(190, 400)
300
(190,400)
40
(25,70)
40
(25, 70)
95.4
95.2
HR (95% CI)
P
value
1.01 (0.95-1.07)
0.83
Operator Annual
Volume
PCI/year
(median, IQR)
Percent Radial PCI
(median, IQR)
PCI Success
• Vascular closure devices used in 26% of Femoral group
RIVAL
Primary and Secondary Outcomes
Radial Femoral
HR
95% CI
P
4.0
0.92
0.72-1.17
0.50
3.2
3.2
0.98
0.77-1.28
0.90
0.7
0.9
0.73
0.43-1.23
0.23
(n=3507)
(n=3514)
%
%
3.7
Primary Outcome
Death, MI, Stroke,
Non-CABG Major
Bleed
Secondary Outcomes
Death, MI, Stroke
Non-CABG Major
Bleeding
RIVAL
Other Outcomes
Radial Femoral
HR
95% CI
P
1.5
0.86
0.58-1.29
0.47
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
(n=3507)
(n=3514)
%
%
Death
1.3
MI
* Post Hoc analysis
RIVAL
Other Outcomes
Radial Femoral
Major Vascular
Access Site
Complications
TIMI Non-CABG
Major Bleeding
ACUITY Non-CABG
Major Bleeding*
* Post Hoc analysis
HR
95% CI
P
(n=3507)
(n=3514)
%
%
1.4
3.7
0.37 0.27-0.52 <0.0001
0.5
0.5
1.00 0.53-1.89
1.9
4.5
0.43 0.32-0.57 <0.0001
1.00
RIVAL
Other Outcomes
Radial
Femoral
(n=3507)
(n=3514)
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
<0.0001
2.6
3.1
0.22
90
49
<0.0001
Persistent pain at access site
>2 weeks (%)
Patient prefers assigned
access site for next
procedure (%)
P
RIVAL
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)
RIVAL
Subgroups: Primary Outcome
Death, MI, Stroke or non-CABG major Bleed
Overall
p-value
Interaction
Age
<75
≥75
Gender
Female
Male
BMI
<25
25-35
>35
Radial PCI Volume/year by Operator
≤70
70-142.5
>142.5
0.79
0.36
0.83
0.54
Radial PCI Volume by Centre
Lowest Tertile
Middle Tertile
Highest Tertile
0.021
Clinical Diagnosis
NSTE-ACS
STEMI
0.025
Radial better
0.25
Femoral better
1.00
Hazard Ratio(95% CI)
4.00
RIVAL
Results stratified by High*, Medium* and Low*
*High (>146 radial PCI/year/ median operator at centre),
Volume radial Centres
Medium (61-146), Low (≤60)
Tertiles of Radial PCI Centre Volume/yr
Primary Outcome
High
Medium
Low
HR (95% CI)
Death, MI or stroke
High
Medium
Low
0.013
Non CABG Major Bleed
High
Medium
Low
0.538
Major Vascular Complications
High
Medium
Low
Access site Cross-over
High
Medium
Low
No significant interaction by Femoral PCI center
volume
p-value
Interaction
0.021
0.019
0.003
0.25
1.00
Radial better
4.00
16.00
Femoral better
RIVAL
Outcomes stratified by STEMI vs. NSTEACS
%
%
2N Radial Femoral
Primary Outcome
NSTE/ACS
STEMI
Interaction
p-value
5063
1958
3.8
3.1
3.5
5.2
0.025
Death, MI or stroke
NSTE/ACS
5063
STEMI
1958
3.4
2.7
2.7
4.6
0.011
Death
NSTE/ACS
STEMI
5063
1958
Non CABG Major Bleed
NSTE/ACS
5063
STEMI
1958
1.2
1.3
0.8
3.2
0.001
0.6
0.8
1.0
0.9
0.56
Major Vascular Complications
NSTE/ACS
5063
1.4
STEMI
1958
1.3
3.8
3.5
0.89
0.25
1.00
4.00
Radial better
Femoral better
Hazard Ratio(95% CI)
Updated Meta-analysis of RCTs
Radial(%)
Femoral(%)
Heterogeneity
p-value
P-value
Non-CABG Major Bleeds
Pre-RIVAL
0.2
1.2
RIVAL
0.7
0.9
Combined
0.5
1.0
0.40
0.002
0.41
<0.0001
0.72
0.17
0.67
0.005
Major Vascular Access Complication
Pre-RIVAL
0.6
2.5
RIVAL
1.4
3.7
Combined
1.0
3.1
2.3
3.3
RIVAL
3.2
3.2
Combined
2.8
3.3
Death,MI or Stroke
Pre-RIVAL
Death, MI or Stroke (Radial Experts)
Pre-RIVAL (Radial Expert
Centre trials)*
2.8
RIVAL(highest radial
1.3
PCI centre tertile)
Combined
2.3
4.1
2.7
3.5
*Radial Expert Centres defined as centres default approach radial or
known expert radial centre
0.25
1.00
4.00
Radial better
Femoral better
Hazard Ratio(95% CI)
RIVAL
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
RIVAL
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
RIVAL
Acknowledgements
RIVAL Program Investigators from 158 sites in 32 countries
Steering Committee
Project Office
Study Team
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
Statisticians and Biometrics
M.G. Franzosi
V. Valentin
R. Afzal (IDMC-Associated)
C. B. Granger
P. Widimsky
P. Gao
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
D. Xavier
X. Yang
DMC
P. Sleight (Chair))
D. R. Holmes Jr.
J.L. Anderson
D.E. Johnstone
D. DeMets
J. Hirsh
L. Xu
E. Dai