Aim of the study

1. A Randomized Comparison of Transradial and Transfemoral Approaches for Coronary Angiography and PTCA in Octogenarians: OCTOPLUS study Y. Louvard, H. Benamer, P. Garot, D. Hildick-Smith, M. Monchi, T. Lefevre, M. Hamon for the OCTOPLUS study group ICPS Massy, CHU “Cote de Nacre” Caen, La Roseraie Aubervilliers, CHU Henri Mondor Creteil, France, Brighton and Sussex UH Brighton, England

2. Aim of the study • This prospective multicentric randomized study was carried out to assess the potential advantages of Transradial (TRA) approach in Octogenarians for diagnostic and intervention procedures

3. Study Centers Participating centers: • ICPS, Institut hospitalier Jacques Cartier and Hopital Claude Galien, Massy and Quincy, France (Y. Louvard, C. Loubeyre, P. Garot, T. Lefevre, O. Tavolaro, P. Dumas) • CHU  Cote de Nacre, Caen, France (M. Hamon, S. Rigattieri R. Sabatier, G. Grollier) • Hopital Europeen de Paris « La Roseraie », Aubervilliers, France (H. Benamer) • Brighton and Sussex University Hospital, Brighton, UK (D. Hildick-Smith)

4. Primary Endpoint Composite approach-related vascular complications leading to a discharge delay: Vascular surgery, any transfusion, Hb loss > 3g/ 100ml or Ht loss > 10%, acute leg or hand ischemia, false aneurysm, forearm compartment syndrome, other vascular complication leading to discharge delay

5. Secondary Endpoints Secondary endpoints: • Previously described approach-related vascular complicationsplus: hematoma > 3 cms in diameter, cholesterol embolism, TIA or stroke, radial artery occlusion • Coronary angiography and PTCA success rates, complications, procedural and X-Ray exposure times, contrast medium volume • Cost analysis: equipment use for diagnosis and intervention, complication related extra-costs (compression device, hospital stay, biological analysis, echo-doppler, transfusion, surgery…)

6. Inclusion / Exclusion criteria, Randomization • 377 Octogenarian patients randomized, after informed consent, to Radial or Femoral approach using a blinded allocation list for each center • Excepted: - double mammary coronary grafting - known occlusion of 2 femoral or arm arteries - previous approach failure • For coronary angiography and/or PCI, whatever the clinical presentation (including AMI) • Before: - femoral pulse evaluation - Hand blood supply evaluation

7. Statistics • Mean + SD • Percentage • Mean comparison with t-test • Percentage comparison with X² • Primer of biostatistics 3.01, Stanton A Glantz • Independent vascular complication predictive factors by multivariate logistic regression analysis

8. Population: clinical data (1)

9. Population: clinical data (2)

10. Population: clinical data (3) Femoral Radial

11. Population: clinical data (4)

12. Procedures

13. Coronary angiography results

14. PCI procedures (1)

15. PCI procedures (2) Excepted in patients presenting with *acute (<24h) or recent ST elevated ACS, Excepted in patients presenting with **any ACS

16. PCI procedures (3)

17. PCI procedures (4)

18. Approach changes

19. Approach changes RADIAL group: Coronary angiography (n) 18 Right Radial to Femoral (n) 15 Right Radial to Left Radial (n) 2 Left Radial to Right Radial (n) 1 PCI (n) 2 Radial to Femoral (ad hoc)(n) 2 (1) FEMORAL group Coronary angiography (n) 15 Femoral to Radial (n) 13 Right Femoral to Left (n) 2 Femoral to Brachial (n) 1 PCI (n) 2 Femoral to Radial (ad hoc)(n) 2 (0)

20. Primary endpoint: Intention to treat analysis *Large hematoma: hospital discharge delay

21. Primary endpoint (Intention to treat analysis): coronary angiography *Large hematoma: hospital discharge delay

22. Primary endpoint (Intention to treat analysis): PCI *Large hematoma: hospital discharge delay

23. Secondary endpoints: coronary angiography

24. Secondary endpoints: PCI

25. Primary endpoint events* * All patients had large hematoma

26. Cross over • Radial to Femoral (%) 8.9 - coronary angiography (%) 8.3 - PCI (%) 2.2 • Femoral to Radial (%) 8.1 - coronary angiography (%) 8.6 - PCI (%) 2.1

27. Primary endpoint, Per protocol analysis *Large hematoma: hospital discharge delay

28. Primary endpoint (per protocol analysis): coronary angiography *Large hematoma: hospital discharge delay

29. Primary endpoint (per protocol analysis): PCI *Large hematoma: hospital discharge delay

30. Primary endpoint (per protocol analysis): PCI and closure devices *Large hematoma: hospital discharge delay 0.006;0.014

31. Predictors of vascular complications in octogenarians: multivariate analysis Twenty-eight data elements selected for analysis Predictors by univariate analysis: femoral approach (p<0.001) small size (p<0.005) female gender (p<0.009) thienopyridine treatment (p<0.09) thrombolysis within 24 hours (p<0.015). Predictors of the primary endpoint by multivariate analysis: femoral approach OR: 22.2 95% CI: 2.4-207.9 p=0.007 thrombolysis w/in 24 h OR: 19.5 95% CI: 2.2-172 p=0.007 patient height <158 cm* OR: 6.4 95% CI: 2.0-20.4 p=0.02 1st height quartile

32. Conclusion (1) • Combined end-point of all approach related vascular complications leading to prolonged hospital stay is significantly lower in Octogenarian randomized to Transradial approach for Coronary angiography and/or PCI compared to Transfemoral approach • Approach related vascular complications are more severe in Femoral randomized group and occur mainly in patients actually approached through Femoral artery (cross overs)

33. Conclusion (2) • Per-protocol analysis shows a higher occurrence rate of the combined end-point and significant blood loss in procedures performed through Femoral artery and a trend for a lower transfusion rate

34. Conclusion (3) • As in younger patients, for coronary angiography, in intention-to-treat analysis, procedural and X-Ray exposure times are slightly but significantly longer in the Transradial group without differences in contrast medium and equipment use • As in youger patients, for PCI, there is no difference in Procedural and X-Ray exposure times, contrast medium volume and equipment use

35. Conclusion (4) • Transradial approach is an effective way to reduce the rate of vascular complications related to coronary angiography and PCI in the high risk octogenarian population

36. Radial vs Femoral coronary angiography: Procedural and X-Ray times Radial: + 20.8% Radial: + 10.6% Radial: + 30% Radial: + 13.2%

37. Radial vs Femoral PCI: Procedural and X-Ray times Radial: + 12.7% Radial: + 6.5% Radial: + 6.5% Radial: - 1%

38. In-Hospital Complications After Multiple Coronary Stenting in Patients >80 Years Old vs <80 Years Old <80 Yrs > 80 Yrs p Value (n 894) (n 75) Death (%) 0.6 2.7 0.10 Cardiac death (%) 0.3 1.3 0.3 Q-wave myocardial infarction (%) 0.1 0 1.0 Urgent coronary bypass (%) 0.6 0 1.0 Non–Q-wave myocardial infarction (%) 20 33 0.008 Pulmonary edema (%) 1.7 8.1 0.004 Acute renal failure (%) 3.5 4.3 0.73 Neurologic event (%) 2.4 6.8 0.04 Vascular complications* (%) 7.3 13.9 0.006 *major hematoma (ht decrease 15%), AV fistula, pseudoaneurysm, retroperitoneal bleeding, surgical repair. GPIIbIIIa inhibitors: 6.8% Kobayashi Lenox Hill Hosp. Am J Cardiol 2003;92:443–446

39. Impact of Access Site Hematoma With Transfusion in Patients Undergoing Percutaneous Coronary Intervention 6613 PCI (98-00)(NHLBI Registry): hematoma w transfusion 1.8% (97% femoral) Predictors: Older age, Lower BMI, Female sex, renal disease, HTN, Acute MI, 3-VD, GPIIb/IIa -, Postprocedure heparin Independent predictors: Older age, female sex, thrombotic lesion, 3-VD, renal disease, emergent PCI, and prior aspirin Procedural death: 10.3% w HWT 1.2% w/o HWT p <0.001 death/MI: 18.1% 3.55% <0.001 HWT is a predictor of death/MI (OR = 3.49; 95% CI: 1.98-6.14) J. Slater Am J Cardiol 2003 (suppl) 92: 18L

40. Coronary Artery Stenting in the Aged Pooled analysis of 6,186 patients in six recent multicenter trials > 80 < 80 p value N= 301 (4.9%) 5885 Death (%) 1.33 0.10 0.001 Myocardial infarction (%) 9.63 7.56 0.18 QMI (%) 0.33 0.68 0.72 Non-QMI (%) 9.30 6.88 0.13 Vascular complications$ (%) 4.98 1.19 0.001 Surgery vasc. Compl. (%) 0.33 0.34 1.00 Bleeding with transfusion* (%) 4.98 1.00 0.001 $access site-related hematoma >4 cm, pseudoaneurysm, AV fistula, retroperitoneal bleed or vascular surgical repair; * blood loss requiring transfusion; GPIIbIIIa: 7.6% Chauhan, J Am Coll Cardiol 2001;37:856–62

41. Predictors of Vascular and/or Bleeding in Aged Variable Univariate Multivariable Odds Ratio Odds Ratio (95% CI) (95% CI) Age (per decade) 1.07 (1.05,1.09) 1.06 (1.04,1.08) In-hosp. Re-revascularization 7.91 (3.29,18.97) 9.94 (3.93,25.15) Female gender 4.40 (2.97,6.64) 3.49 (2.31,5.27) Diabetes 1.25 (0.81,1.92) — Unstable angina 1.39 (0.96,2.02) — c = 0.759, Hosmer-Lemeshow x2 p = 0.377 Chauhan, J Am Coll Cardiol 2001;37:856–62

42. Outcome Trends in the Elderly Undergoing Percutaneous Coronary Interventions: Results in 7,472 Octogenarians Outcome Age >80 Age <80 Odds Ratio p Value N= 7472 102236 (95% CI) Death 3.8 (3.4–4.2) 1.1 (1.0–1.1) 3.6 (3.2–4.1) 0.001 Procedural success 84 (83–85) 89 (89–89) 0.65 (0.60–0.70) 0.001 Death/MI/CVA 4.9 (4.4–5.4) 1.9 (1.9–2.0) 2.6 (2.3–2.9) 0.001 Q wave MI 1.9 (1.5–2.3) 1.3 (1.2–1.3) 1.5 (1.2–1.9) 0.001 CVA 0.58 (0.38–0.78) 0.23 (0.2–0.26) 2.5 (1.7–3.6) 0.001 Renal failure 3.2 (2.7–3.7) 1.0 (0.96–1.1) 3.1 (2.6–3.8) 0.001 Vascular complication 6.7 (6.0–7.5) 3.3 (3.2–3.5) 2.1 (1.9–2.4) 0.001 Urgent revasc. 4.4 (4.0–4.9) 4.5 (4.4–4.6) 0.98 (0.88–1.1) 0.770 Total LOS† 5.1+5.3 3.7+4.3 NA 0.001 Postprocedure LOS† 3.6+4.6 2.6+3.8 NA 0.001 Batchelor J AmColl Cardiol 2000;36:723–30

43. Outcome Trends in the Elderly Undergoing Percutaneous Coronary Interventions: Results in 7,472 Octogenarians Relative odds with 95% CI for each year compared with 1994. The ORs presented have been adjusted for the seven variables in the multivariable mortality risk model. Batchelor J AmColl Cardiol 2000;36:723–30

44. Predicting vascular complications in percutaneous coronary interventions 18,137 PCI pts in northern New England (1997-1999); vascular complication* 2.98% Variables associated with increased risk in the multivariate analysis Age >or=70 OR 2.7 Female sex OR 2.4 Body surface area <1.6 m OR 1.9 History of congestive heart failure OR 1.4 Chronic obstructive pulmonary disease OR 1.5 Renal failure OR 1.9 Lower extremity vascular disease OR 1.4 Bleeding disorder OR 1.68 Emergent priority OR 2.3 Myocardial infarction OR 1.7 Shock OR 1.86 >or=1 type B2 lesions OR 1.32 type C lesions OR 1.7 3-vessel PCI OR 1.5 Thienopyridines OR 1.4 Glycoprotein IIb/IIIa inhibitors OR 1.9 *Vascular complications: access-site injury requiring treatment or bleeding requiring transfusion Piper WD Am Heart J. 2003 Jun;145(6):1022-9

45. Complications of Cardiac Catheterization in Octogenarians (94-97), 5737 inpatient Cardiac Catheterization: 5.9% octogenarians In-hospital post Cardiac catheterization complications Age <80 Age >80 N= 5399 338 p Value Male (%) 65 51 <0.001 Emergency CABG (%) 0.6 1.2 NS Post CC MI (%) 0.2 0.9 0.02 Inpatient death (%) 0.8 4.4 <0.001 CVA (%) 0.2 0.3 NS Groin hematoma (%) 0.6 3.6 <0.001 Pseudoaneurysm (%) 0.4 1.2 0.04 Surgery for pseudo. (%) 0.0 0.3 0.001 Retroperitoneal bleed (%) 0.1 0.0 NS SztoAm J Cardiol 1998; 84(supp1 6A): 25S

46. Complication rates related to cardiac catheterization in 1070 consecutive patients older than 80 years 1070 consecutive patients > 80 years 1295 cardiac catheterizations (1995-2000) Access site related complications (pts): 2.7% 13 extensive hematoma 10 pseudoaneurysms 4 AV fistulas 1 embolus to the popliteal artery = 6 transfusion and 10 surgical repair Niebauer Eur Heart Journal 2001; 22, Abstr. page 202