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 complications plus: 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) FemoralRadialp value n=185192 Age (y)83.0+3.182.6+2.7ns Male (%)50.855.2ns Dyslipidemia (%)43.236.5ns Hypertension (%)65.257.8ns Diabetes (%)18.48.90.011 Smoking (%)5.45.2ns Weight (%)68+1068+12ns Height (%)164+8164+9ns Creatininemia (µmole/L)114+50108+40ns

9. FemoralRadialp value n=185192 Previous MI (%)21.615.6Ns Previous PCI (%)24.314.60.024 Previous Bypass surg. (%)10.87.9Ns Previous Coro. Angio. (%)35.727.1Ns Population: clinical data (2)

10. FemoralRadial Population: clinical data (3)

11. FemoralRadialp value n=192185 Aspirin (%)78.374.0ns Vitamin K – (%)4.96.9ns LMWH (%)5.58.5ns GPIIb/IIIa – (%)10.313.3ns Thrombolytics < 24h2.24.3ns Population: clinical data (4)

12. FemoralRadialp value n=185192 Coronary angiography (n / %)175 / 94.6180 / 93.7ns + « Ad hoc » PCI (n /%)87 / 47.077 / 40.1ns Total PCI (n / %)97 / 52.489 / 46.6ns Procedures

13. Coronary angiography results FemoralRadialp value n=175180 Normal14.917.2ns 1 vessel disease26.519.4ns 2 vessel disease20.725.6ns 3 vessel disease38.437.8ns Prox LAD stenosis46.748.9ns Left main stenosis10.716.3ns LVEF58+1459+13ns

14. PCI procedures (1) FemoralRadialp value n=9789 Dilated lesions (n)1.5+0.71.4+0.8ns Dilated vessels (n)1.2+0.51.2+0.4ns GPIIb/IIIa per proced. / Total (%)12.410.5ns ACT (sec.)250+62277+106ns Femoral hemostatic devices51.46.7<0.000

15. FemoralRadialp value n=9789 Primary success (%)95.896.6ns Em. Bypass (%)3.10ns Q MI (*Exc. ST+ ACS)(%)23.7 (0)21.3 (0)ns Non Q MI (**Exc. ACS)(%)16.7 (5.2)14.6 (1.1)ns In-hospital Death (%)3.24.3ns CK (UI)401+803518+869ns Excepted in patients presenting with *acute (<24h) or recent ST elevated ACS, Excepted in patients presenting with **any ACS PCI procedures (2)

16. FemoralRadialP value Lesions n=143128ns LAD (%)42.045.3ns Circomflex (%)23.116.4ns RCA (%)24.531.2ns LM (%)2.82.3ns PCI procedures (3)

17. FemoralRadialP value Lesions n=143128ns Restenosis (%)9.93.20.051 Acute occlusion (%)13.44.20.015 CTO (%)8.86.0ns Stent (%)90.995.3ns Stent number (n)1.3+0.71.2+0.6ns Direct stenting (%)43.957.00.051 Max. balloon diameter (mm)3.2+1.53.2+0.6ns Max. balloon pressure (atm)14+315+3ns Angiographic success (%)97.197.6ns PCI procedures (4)

18. Approach changes

19. 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) Approach changes

20. Primary endpoint: Intention to treat analysis FemoralRadialp value n=185192 COMPOSITE END-POINT (%)6.51.60.029 Vasc. Surgery (%)00.5ns Transfusion (%)1.61.0ns Hb drop > 3g/DL (%)3.80.50.063 False aneurysm compression (%)1.10.5ns Arm or leg ischemia (%)00ns Forearm compartment syndrom (%)00ns Large hematoma* (%)6.51.60.031 Hematoma (%)11.43.50.003 CVA (%)0.60ns *Large hematoma: hospital discharge delay

21. Primary endpoint (Intention to treat analysis): coronary angiography FemoralRadialp value n=88103 COMPOSITE END-POINT (%)4.51ns Vasc. Surgery (%)01ns Transfusion (%)1.11.0ns Hb drop > 3g/DL (%)3.51ns False aneurysm compression (%)1.11ns Large hematoma* (%)4.51ns Hematoma (%)10.51.90.027 CVA (%)1.20ns *Large hematoma: hospital discharge delay

22. FemoralRadialp value n=9789 COMPOSITE END-POINT (%)8.22.2ns Vasc. Surgery (%)00.5ns Transfusion (%)2.11.1ns Hb drop > 3g/DL (%)4.10ns False aneurysm compression (%)1.00ns Large hematoma* (%)7.22.1ns Hematoma (%)12.44.50.1 CVA (%)00ns *Large hematoma: hospital discharge delay Primary endpoint (Intention to treat analysis): PCI

23. Secondary endpoints: coronary angiography FemoralRadialp value n=175180 Selective LCA angio. (%)99.4100ns N° of catheters (n)1.1+0.41.2+0.5ns Selective RCA angio. (%)97.198.8ns N° of catheters (n)1.1+0.41.1+0.5ns Total N° of coro. cath. (n)2.2+0.92.1+0.9ns Procedural time (min.)15.9+9.518.5+10.50.015 X-Ray exposure time (min.)4.5+3.76.0+4.4<0.001 Contrast medium (cc)114+62119+61ns

24. FemoralRadialp value n=9789 N° of guiding catheters (n)1.8+1.11.6+0.9ns Procedural time (Min.)33.8+22.634.6+21.6ns X-Ray exposure time (Min.)10.7+9.811.6+9.4ns Contrast medium (cc)165+119150+110ns Secondary endpoints: PCI

25. RandomActualProcedureSurgTransfF. aneurHb >- 3g/DL Comments RAD Coro+PCI RADFEMCoro+PCIX RADFEMCoroXXXX FEM CoroXXAnuria, Death FEM CoroXX FEM Coro FEM Coro FEM Coro+PCI FEM Coro+PCIX FEM Coro+PCI FEM Coro+PCI FEM Coro+PCIXXXICU 8d FEM Coro+PCIXXRenal failure, ICU 13d FEM Coro+PCI FEM Coro+PCI * All patients had large hematoma Primary endpoint events*

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

27. Primary endpoint, Per protocol analysis FemoralRadialp value n=186190 COMPOSITE END-POINT (%)7.50.50.001 Vasc. Surgery (%)0.50ns Transfusion (%)2.700.067 Hb drop > 3g/DL (%)4.400.01 False aneurysm compression (%)1.60ns Arm or leg ischemia (%)00ns Forearm compartment syndrom (%)00ns Large hematoma* (%)7.60.50.001 Hematoma (%)10.93.70.013 CVA (%)0.60ns *Large hematoma: hospital discharge delay

28. Primary endpoint (per protocol analysis): coronary angiography FemoralRadialp value n=89101 COMPOSITE END-POINT (%)5.600.051 Vasc. Surgery (%)00ns Transfusion (%)1.10ns Hb drop > 3g/DL (%)3.50ns False aneurysm compression (%)1.10ns Large hematoma* (%)5.600.051 Hematoma (%)10.31.90.034 CVA (%)1.20ns *Large hematoma: hospital discharge delay

29. FemoralRadialp value n=9789 COMPOSITE END-POINT (%)9.31.10.031 Vasc. Surgery (%)00ns Transfusion (%)3.10ns Hb drop > 3g/DL (%)4.10ns False aneurysm compression (%)1.00ns Large hematoma* (%)8.21.10.055 Hematoma (%)11.35.6ns CVA (%)00ns Primary endpoint (per protocol analysis): PCI *Large hematoma: hospital discharge delay

30. RadialFemoral Closure+ Femoral Closure- n=895641 COMPOSITE END-POINT (%)1.15.414.6 Vasc. Surgery (%)000 Transfusion (%)007.3 Hb drop > 3g/DL (%)009.8 False aneurysm compression (%)002.4 Large hematoma* (%)1.15.47.3 Hematoma (%)5.67.117.1 0.006; 0.014 Primary endpoint (per protocol analysis): PCI and closure devices *Large hematoma: hospital discharge delay

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 1 st 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. 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 Conclusion (2)

34. 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 Conclusion (3)

35. 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 Conclusion (4)

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

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

38. In-Hospital Complications After Multiple Coronary Stenting in Patients >80 Years Old vs <80 Years Old 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 Kobayashi Lenox Hill Hosp. Am J Cardiol 2003;92:443–446 *major hematoma (ht decrease 15%), AV fistula, pseudoaneurysm, retroperitoneal bleeding, surgical repair. GPIIbIIIa inhibitors: 6.8%

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 Chauhan, J Am Coll Cardiol 2001;37:856–62 $access site-related hematoma >4 cm, pseudoaneurysm, AV fistula, retroperitoneal bleed or vascular surgical repair; * blood loss requiring transfusion; GPIIbIIIa: 7.6%

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. 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 Outcome Trends in the Elderly Undergoing Percutaneous Coronary Interventions: Results in 7,472 Octogenarians

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 Piper WD Am Heart J. 2003 Jun;145(6):1022-9 *Vascular complications: access-site injury requiring treatment or bleeding requiring transfusion

45. Complications of Cardiac Catheterization in Octogenarians (94-97), 5737 inpatient Cardiac Catheterization: 5.9% octogenarians In-hospital post Cardiac catheterization complications 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 Szto Am 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