Results from the Randomized Multicentre Radial Artery Patency Study (RAPS)

The Radial Artery Patency Study Investigators

Radial Artery and Saphenous Vein Radial Artery and Saphenous Vein Patency more than 5-years Following Patency more than 5-years Following

Coronary Artery Bypass Surgery: Coronary Artery Bypass Surgery:

Results from the Results from the Randomized Multicentre Randomized Multicentre

Radial Artery Patency Radial Artery Patency Study (RAPS)Study (RAPS)

Funded by CIHR Grant: MCT 52681 Funded by CIHR Grant: MCT 52681 NCT00187356 NCT00187356


Stephen E. Fremes MD, Saswata Deb MD, Stephen E. Fremes MD, Saswata Deb MD, Steve K. Singh MD, Randi Feder-Elituv Steve K. Singh MD, Randi Feder-Elituv BSc, Andreas Laupacis MD and Eric A. BSc, Andreas Laupacis MD and Eric A.

Cohen MD for the Radial Artery Patency Cohen MD for the Radial Artery Patency Study InvestigatorsStudy Investigators

April 4, 2001April 4, 2001

New Orleans, LANew Orleans, LA


BackgroundBackground Graft patency is a key determinant of

long term outcome following coronary artery bypass surgery (CABG)

The internal thoracic artery provides better long-term patency than the saphenous vein for CABG, prompting surgeons to consider additional arterial grafts, including the radial artery



Study QuestionStudy Question

Is the patency of the radial Is the patency of the radial artery superior to the artery superior to the saphenous vein at one saphenous vein at one

year?year?


PatientsPatientsInclusion Criteria:Inclusion Criteria:

GeneralGeneral <80 years old<80 years old Isolated triple vessel Isolated triple vessel

diseasedisease LV Ejection Fraction > 35%LV Ejection Fraction > 35%

AngiographicAngiographic >70% stenosis of target >70% stenosis of target

RCA and LCXRCA and LCX RCA and LCX graftable RCA and LCX graftable

and >1.5mmand >1.5mm

Exclusion Criteria:Exclusion Criteria:

Inability to use Radial Inability to use Radial or Venous Conduit:or Venous Conduit:

Positive Allen’s Test or abnormal Positive Allen’s Test or abnormal ultrasound, vasculitis or Raynaud’s ultrasound, vasculitis or Raynaud’s

Bilateral varicose veins and/or strippingBilateral varicose veins and/or stripping

Contraindications to Contraindications to Angiography:Angiography:

Creatinine > 180 Creatinine > 180 μμmol/Lmol/L Severe PVDSevere PVD Contrast allergy dyeContrast allergy dye Geographic inaccessibilityGeographic inaccessibility


Study Study RandomizationRandomization

RCA:RCA:RADIAL RADIAL

OrOrSVGSVG

LCX:LCX:SVGSVG

ororRADIALRADIAL

Randomization was performedRandomization was performed withinwithin patients not patients not between between patientspatients

LIMA to LADLIMA to LAD


PRIMARY STUDY ENDPOINT:PRIMARY STUDY ENDPOINT:Graft Occlusion at 1 YearGraft Occlusion at 1 Year

Occluded = No Opacification of Distal Vessel (TIMI 0)

OR 0.56OR 0.5695% CI 0.34–0.8895% CI 0.34–0.88

Absolute Difference Absolute Difference =5.4%=5.4%

8.213.6

0

5

10

15

20

25

RADIALS VEINS

% O

cclu

ded

Gra

fts

McNemar

p = 0.009

Intention to Treat AnalysisIntention to Treat Analysis

NEJM Nov. 25, 2004


SECONDARY STUDY ENDPOINT:SECONDARY STUDY ENDPOINT:Functional Graft Occlusion at 1 Year Functional Graft Occlusion at 1 Year

TIMI 3 = Patent TIMI 0,1,2 = Occluded

12.3 14.3

0

5

10

15

20

25

RADIAL SVG

% O

cclu

ded

Gra

fts

McNemar

p = 0.37

Intention to Treat AnalysisIntention to Treat Analysis

NEJM Nov. 25, 2004


Study QuestionStudy Question

Is the patency of the radial Is the patency of the radial artery superior to the artery superior to the saphenous vein > 5 saphenous vein > 5

years following surgery?years following surgery?


Randomized N=561

13 centres

N=52911 centres

N=5019 centres

2 centres, N=32

2 centres, N=20Deaths < 1 yr, N=8

Clinical Follow-Up

Enrollment

Angiographic Follow-

Up

Study Patients Study Patients


EligibleN=501

N=483

N=369

Protocol Violations, N=162 Study Grafts Occluded,

N=4

Death 1-5 yrs, N=10New Med Exclusions, N= 64

Distance to Centre, N=9 LTFU, N=31

N=269

Death 5-6 yrs, N=6Patient Refusal, N=94

Study Patients Study Patients

Analysis

Eligible for Analysis


Study PatientsStudy Patients

Variable Angiography, n=269

No Angiography, n=260

Age (yrs) 60.4 + 8.0 61.8 + 8.7 *

Age > 70 yrs (%) 11.9 18.4 *

Female (%) 15.2 11.5

Urgent (%) 34.6 35.4

CCS Class 3-4 (%) 51.3/26.7 43.1/27.7

Diabetes (%) 30.9 25.0

Hypertension (%) 45.0 53.5

Vascular Disease (%) 6.0 11.5 *

Creatinine (mol/L) 92.1 + 18.2 93.6 + 22.3


Angiographic Angiographic ResultsResults


PRIMARY STUDY ENDPOINT:PRIMARY STUDY ENDPOINT:Functional Graft Occlusion at 5 YearsFunctional Graft Occlusion at 5 Years

TIMI 3 = Patent TIMI 0,1,2 = Occluded

OR 0.64OR 0.6495% CI 0.41-0.9895% CI 0.41-0.98

Absolute Absolute Difference =6.8%Difference =6.8%

12.0

18.8

0

5

10

15

20

25

RADIAL SVG

% O

cclu

ded

Gra

fts

McNemar

p = 0.05

Intention to Treat Analysis, n=234Intention to Treat Analysis, n=234


SECONDARY STUDY ENDPOINT:SECONDARY STUDY ENDPOINT:Graft Occlusion at 5 YearsGraft Occlusion at 5 Years


OR 0.50OR 0.5095% CI 0.32-0.8095% CI 0.32-0.80

Absolute Absolute Difference =8.9%Difference =8.9%

8.9

17.8

0

5

10

15

20

25

RADIAL SVG

% O

cclu

ded

Gra

fts

McNemar

p = 0.004



SECONDARY STUDY SECONDARY STUDY ENDPOINT:ENDPOINT:

Graft Stenosis >25% of TIMI 3 GraftsGraft Stenosis >25% of TIMI 3 Grafts N=164 both grafts patentN=164 both grafts patent

Proximal Anastomosis:Proximal Anastomosis: Radial 9.8%Radial 9.8% SVG 9.8%SVG 9.8%

Graft Body: Graft Body: Radial 6.7%Radial 6.7% SVG 15.2%, p=0.02, SVG 15.2%, p=0.02,

OR 0.42, 95% CI 0.18 – 0.90OR 0.42, 95% CI 0.18 – 0.90 Distal Anastomosis: Distal Anastomosis:

Radial 6.1%Radial 6.1% SVG 6.7%SVG 6.7%


SECONDARY STUDY ENDPOINT:SECONDARY STUDY ENDPOINT:Graft Stenosis >25% or Occlusion Graft Stenosis >25% or Occlusion


OR 0.58OR 0.5895% CI 0.40-0.8695% CI 0.40-0.86

Absolute Difference Absolute Difference =11.9%=11.9%

21.933.8

01020304050

RADIAL SVG

% O

cclu

ded

G

raft

s

McNemar

p = 0.004



Clinical ResultsClinical Results


MACEMACEOutcome < 30 days,

n=56131 days-1 year,

n=561> 1 year,

n=529

Death 4 (0.7) 4 (0.7) 52 (10.0)

Cardiac Death

3 (0.5) 2 (0.4) 26 (4.9)

Non-fatal MI 55 (9.8) 1 (0.2) 8 (1.5

Redo CABG 0 0 2 (0.4)

PCI 0 4 (0.7) 24 (4.5)

Composite Endpoint

59 (10.5) 9 (1.2) 79 (14.9)


SurvivalSurvival

0.0

0.1

0.2

0.3

0.4

0.5

0.6

0.7

0.8

0.9

1.0

0 2 4 6 8 10 12 14TIME (YRS)

Su

rviv

al

5 years 0.96 + 0.01

7.5 years 0.91 + 0.02

10 years 0.82 + 0.03


Event-Free SurvivalEvent-Free Survival

0.0

0.1

0.2

0.3

0.4

0.5

0.6

0.7

0.8

0.9

1.0

0 2 4 6 8 10 12 14TIME (YRS)

Su

rviv

al

5 years 0.95 + 0.01

7.5 years 0.90 + 0.02

10 years 0.78 + 0.03


LimitationsLimitations The study design restricted our ability The study design restricted our ability

to evaluate the clinical consequences to evaluate the clinical consequences of radial and saphenous grafts.of radial and saphenous grafts.

The patients recruited into the study The patients recruited into the study were young, and generally low risk.were young, and generally low risk.


Conclusions: 5 Year ResultsConclusions: 5 Year Results

Radial arteries are associated with Radial arteries are associated with reduced rates of functional and reduced rates of functional and complete graft occlusion than complete graft occlusion than saphenous veins. saphenous veins.

Radial arteries are associated with Radial arteries are associated with less graft disease than saphenous less graft disease than saphenous veins.veins.


Clinical Trials of Radial Clinical Trials of Radial PatencyPatency

RAPS, Multi-centre, 561 patients, within-patient randomization, Radial vs SVG to RCA or Cx, NEJM 2004

ISRS (Italy) Single centre, 60 ISRS patients and 60 controls, RA, RITA or SVG to OM1 Circulation 2005; 112(supp I):I-265-9

RSVP (UK) Single centre, 142 patients, Radial vs SVG to Cx, Circulation 2008; 117: 2859 - 2864

VA Trial, Multi-centre, 757 patients, Radial vs SVG to 2nd largest coronary, JAMA 2011

RAPCO (Australian), Single centre, 619 patients, <70 years, Radial vs free RITA to 2nd largest coronary >70 years, Radial vs SVG to 2nd largest coronary 4 manuscripts published concerning “interim” results


Additional slides

1 year and 5 year results for patients with both studies

Actuarial survival Mace, including adjudicated outcomes


PARTICIPATING CENTRESSUNNYBROOK HEALTH SCIENCES

CENTRETORONTO, ON

VANCOUVER GENERAL HOSPITAL

VANCOUVER, BC

Dr. Stephen Fremes Dr. Guy FradetDr. Eric Cohen Dr. Chris Buller

Randi Elituv Rebecca Fox/Neetha Hsu

LONDON HEALTH SCIENCES CENTRE LONDON, ON TORONTO GENERAL HOSPITAL TORONTO, ONDr. Richard Novick Dr. Terry YauDr. David Almond Dr. Len Schwartz

Stephanie Fox Katherine Tsang/Chet Nacario

LONDON HEALTH SCIENCES CENTRE LONDON, ON UNIVERSITY OF ALBERTA ON EDMONTON, ABDr. Mary Lee Myers Dr. Elliot GelfandDr. David Almond Dr. Wayne Tymchak

Mary-Ann James/Linda HerrisMONTREAL HEART INSTITUTE MONTREAL, QC

Dr. Raymond Cartier MONTREAL GENERAL HOSPITAL MONTREAL, QCDr. Gilles Cote Dr. Jean Francois MorinCarole Jesina Dr. Dragatkis

Sybil GermainOTTAWA HEART INSTITUTE OTTAWA, ON

Dr. Frasier RubensWINNIPEG HEALTH SCIENCES

CENTREWINNIPEG, MB

Dr. Lyall Higginson Dr. Michael RaabeSharon Finlay/Sarika Naidoo Dr. John Ducas

Angie Munoz/Lisa MontebrunoST. MICHAEL’S HOSPITAL TORONTO, ON

Dr. David LatterDr. Randy Watson

Mary Keith/Rose Mokbel

Documents

Results from the Randomized Multicentre Radial Artery Patency Study (RAPS)