Radial Artery Patency and Clinical Outcomes Study: a tale of two trials BRIAN BUXTON and philip hayward University of Melbourne, EPWORTH and Austin Hospitals, Melbourne SCTS University 2016

Radial Artery RCTs: RAPCO : Melbourne 1996-2005 RAPS: Toronto 1996-2001 RSVP: London 1998-2000 VA: USA 2003-2009 SCTS University 2016

Radial Artery Patency and Clinical Outcomes Study Randomization of RA, RITA or SV for the 2nd graft in primary isolated CABG gold standard in situ LITA to LAD graft unchanged 3rd and 4th grafts as per surgeon preference Standardized surgery and perioperative care to assess impact of conduit selection all conduits treated alike as aortocoronary grafts AATS 2016

Radial Artery Patency and Clinical Outcomes: 2 parallel trials Age ≤70 years (≤60 years if diabetic) radial artery vs free RITA powered for 10% difference in patency with 10% loss Age >70 years (>60 years if diabetic) radial artery vs saphenous vein powered for 15% difference in patency with 10% loss AATS 2016

RA vs RITA: age ≤70 (≤60 diabetic) Group 1 Enrolment 1996-2005 Randomization group RA RITA P Assessment n=980 Exclusion n=586 Randomized 198 196 Received allocation 186 179   Age (mean & range) 59.2 (36.9 - 71.0) 59.5 (36.2 - 70.9) 0.72* Gender (male) 175 (88%) 178 (91%) 0.51** Diabetes 22 (11%) 21 (11%) 1.0** Hypertension 113 (57%) 99 (51%) 0.23** Elective presentation 160 (81%) 161 (82%) 0.80** No. of grafts (mean ± std dev) 3.2 ± 1.0 0.49* Smoking history 148 (75%) 143 (73%) 0.73** MI pre surgery 75 (38%) 68 (35%) 0.53** SCTS University 2016

Clinical and Angiographic Follow up 10 years of annual follow up by cardiologist and trial nurse survival / MI / PCI / surgery Graft angiogram at a randomized time point between 1 month and 10 years Optional supplemental study (CT) at 5 and 10 years

RA vs RITA: 10-year angiographic outcome Group 1 89% RA vs RITA p = .057 80% Sig Hazard 95% CI Lower Upper Log Rank .057 K-M Cox regression .061 1.86 .97 3.58 Figure 4 Number at risk: 169 159 153 109 71 33 157 156 142 84 56 31 AATS 2016 Group 1

Revascularisation (%) RA vs RITA 10-Year Clinical Follow Up Death (%) MI (%) Revascularisation (%) RA (n=198) 18 (9) 11 (6) 22 (11) RITA (n=196) 32 (16) 13 (7) 26 (13) 91% RA vs RITA p = .032 84% RA vs RITA p = .084 Sig RR 95% CI Lower Upper Cox regression .035 1.86 1.05 3.31 Figure 2 Number at risk: 198 194 191 189 183 179 196 193 186 178 172 164 Number at risk: 198 190 185 176 168 153 196 191 179 163 148 138 Group 1 survival Group 1 event free survival SCTS University 2016

RA vs SV: age >70 (>60 diabetic) Group 2 Enrolment 1996-2005 Randomisation group RA SV p Assessment n=902 Exclusion n=677 Randomized 113 112 Received allocation 186 179   Age (mean & range) 72.6 (61.0 - 83.5) 73.1 (60.5 - 80.7) 0.43* Gender (male) 91 (81%) 1.0** Diabetes 50 (44%) 52 (46%) 0.79** Hypertension 68 (60%) 78 (70%) 0.16** Elective presentation 87 (77%) 0.51** No. of grafts (mean ± std dev) 3.2 ± .9 3.3 ± .7 0.26* Smoking history 75 (66%) 76 (68%) 0.89** MI pre surgery 43 (38%) 36 (32%) 0.40** SCTS University 2016

RA vs SV: angiographic outcomes Group 2 91% b: Group 2 RA vs SVG p = .029 81% Sig Hazard 95% CI Lower Upper Log Rank .029 K-M Cox regression .037 2.87 1.07 7.71 Figure 4 Number at risk: 78 70 66 40 23 11 68 61 57 29 17 5 AATS 2016

Revascularisation (%) RA vs SV: 10 year Clinical Outcomes Death (%) MI (%) Revascularisation (%) RA (n=113) 31 (27) 8 (7) 7 (6) SV (n=112) 39 (35) 10 (9) 9 (8) 73% RA vs SVG p = .24 RA vs SVG p = .18 65% Sig RR 95% CI Lower Upper Cox regression .24 1.33 .83 2.12 Figure 3 Number at risk: 113 108 103 100 94 82 112 109 106 99 87 72 Number at risk: 113 106 101 96 86 71 112 98 88 73 61 Group 2 survival Group 2 event free survival SCTS University 2016

RA ≥ RITA 10-year estimates of patency RA: 89 +/- 2.9% log rank p=0.057 RITA: 80 +/- 3.9% HR for failure : 1.86 (0.97-3.58, p=0.061) Why might radial artery be superior ? less easily traumatized adequate length proximal anastomosis similar to SV AATS 2016

RA > SV 10 year estimates of patency Comparable to other trials RA: 85 +/- 6.8% log rank p= 0.029 SV: 70 +/- 9.8% HR for failure : 2.87 (1.07-7.71, p=0.037) Comparable to other trials RAPS Toronto: 269 /510 patients: RA 87% vs SV 79% at 7.7 years RSVP London: 103/142 patients: RA 94% vs SV 79% at 5 years AATS 2016

Discussion The radial artery may be superior to the free RITA or saphenous vein for the second graft Coronary bypass is the commonest procedure 9-10% difference in patency in 2nd graft (? 3rd / 4th) at least one patient per month for typical surgeon AATS 2016

Radial Artery Patency and Clinical Outcome trials

Acknowledgements The authors publish on behalf of all who have contributed to the RAPCO study. Participating Surgeons Prof Brian Buxton, A/Prof George Matalanis, Mr Alexander Rosalion, Prof Jai Raman, Mr Siven Seevanayagam, Mr Jullien Gaer, Mr Justin Negri, Dr Masashi Komeda   Anaesthesia and Critical Care Prof Rinaldo Bellomo, Dr Laurie Doolan, A/Prof Larry McNicol Interventional Cardiologists Dr John Brennan, Dr Robert Chan, Dr David Clark, Dr Ronald Dick, Dr Anthony Dortimer, A/Prof David Ecclestone, A/Prof Omar Farouque, Dr Dharsh Fernando, Dr Mark Horrigan, Dr Anthony Jackson, Dr Jennifer Johns, Dr Paul Kertes, Dr Leslie Oliver, Dr Nilesh Mehta, Dr Voltaire Nadurata, Dr Nim Nadarajah, Dr George Proimos, Dr Michael Rowe, Dr Ben Sia, Dr Christopher Webb Clinical Cardiologists Dr Nagesh Anaveker, A/Prof Peter Barlis, A/Prof Paul Calafiore, Dr Boniface Chan, Dr John Cotroneo, Dr Angas Hamer, Prof David Hare, Dr Elizabeth Jones, Dr David O’Donnell, Dr Stephen Sylviris, Prof Andrew Tonkin Coronary CT radiologists Dr Robert Fabini, Dr Leighton Kearney, Dr Ruth Lim, Dr Maurice Molan, Dr Gerard Smith, Dr Chris Wellman, Dr John Eng Statistical and Data Management: Dr Ian Gordon, Margaret Shaw, Sandra Gerbo

Clinical and Angiographic Follow up 10 years of annual follow up by cardiologist and trial nurse survival / MI / PCI / surgery Graft angiogram at a randomized time point between 1 month and 10 years Optional supplemental study (CT) at 5 and 10 years

30 day outcomes were equal Group 1 Death <30 days MI Sternal infection Return to OR for bleeding Ventilation >24 hrs Group 1 RA (n=198) 1 4 Group 1 RITA (n=196) 3 Group 2 RA (n=113) 2 Group 2 SV (n=112) Short term morbidity was unrelated to conduit type, p=ns AATS 2016

Return to OR for bleeding 30 day outcomes were safe Group 2 Death <30 days MI Sternal infection Return to OR for bleeding Ventilation >24 hrs Group 1 RA (n=198) 1 4 Group 1 RITA (n=196) 3 Group 2 RA (n=113) 2 Group 2 SV (n=112) Short term morbidity was unrelated to conduit type, p=ns AATS 2016