CYPHER is Preferred in Diabetics Stephan Windecker University
CYPHER is Preferred in Diabetics! Stephan Windecker University Hospital Bern Switzerland
Conflict of Interest Statement Within the past 12 months, I or my spouse/partner have had a financial interest/arrangement or affiliation with the organization(s) listed below. Physician Name Company/Relationship Stephan Windecker Biotronik (Consultant) Cordis (Consultant) Boston Scientific (Speakers Bureau) Abott (Speakers Bureau)
Risk of Restenosis in the Bare Metal Stent Era Diabetic vs Nondiabetic Patients P=0. 001 P=ns P=0. 02 P=0. 001 P<0. 001 N=2255 N=1439 OR=1. 6 1. 4 -1. 9 P<0. 001 % N=230 N=300 N=84 N=4808
Mechanism of Restenosis in Diabetic Patients Late Loss Neointimal Hyperplasia Elezi S et al. JACC 1998; 32: 1866 Kornowski et al. Circulation 1997; 95: 1366 P<0. 001 Intimal Hyperplasia (%) Late Loss (mm) P<0. 001
Impact of Restenosis on Prognosis in Diabetic Patients ! y t i Van Belle E et al. Circulation 2001; 103: 1218 l a rt o M f P<0. 001 o r o t c i d e r P t en Mortality Elezi S et al. JACC 1998; 32: 1866 P<0. 001 (%) d n e p de P=0. 04 In : is s o Re n e t s Mortality @ 10 years (%) Restenosis 603 diabetic patients undergoing PTCA between 1987 -1995
DIABETES: Randomized Comparison of CYPHER vs Bare Metal Stent in Diabetic Patients Sabate M et al. Circulation 2005; 112: 2175 -83 RVD: 2. 34 mm; Mean lesion length: 15. 0 mm mm Late Loss P<0. 001 N=103 N=101 Restenosis % 77% P<0. 001 N=103 N=101 TLR % 72% P<0. 001 N=80
Indirect Comparison of Randomized Trials With CYPHER vs TAXUS Stratified According to DM Stettler C et al. Heart 2006; 92: 650 -7 SES DM Non-DM Age Female RVD SIRIUS E-SIRIUS C-SIRIUS DIABETES RAVEL SES-SMART Total (N) 279 81 24 160 44 64 652 778 271 76 194 193 1458 62 62 61 67 61 64 29% 31% 38% 24% 28% 2. 80 2. 55 2. 63 2. 34 2. 62 2. 20 2. 52 PES DM Non-DM Age Female F/u TAXUS II TAXUS IV TAXUS VI Total (N) 11 76 318 89 494 49 453 996 357 1885 65 60 63 63 11% 24% 28% 24% 2. 97 2. 75 2. 78 2. 81
Indirect Comparison of Randomized Trials With ) CYPHER vs TAXUS Stratified According to DM S U Stettler C et al. Heart 2006; 92: 650 -7 X A T ( Non-Diabetic Patients 1 mm. 8 2 P=0. 03 = D V R s P=0. 045 v ) R E H Diabetic Patients P Y (C m P=0. 31 m 2 5. 2 P=0. 70 = D RV Relative Risk Reduction (%)
Problems With Indirect Comparisons and Registries • Different definitions of TLR/TVR – CYPHER: • Symptoms and DS% >50% • Asymptomatic and DS% >70% – TAXUS: • Ischemia and DS% >50% • Symptoms and DS% >70% • Different rates of follow-up angiography – SIRIUS: 66% – TAXUS IV: 43%
RESEARCH vs T-SEARCH Ong A et al. JACC 2005; 45: 1135 -41 Real World Registry Protocol-driven repeat angiography in the following subgroups: SES (40%) -LM -Bifurcation -CTO -very small vessels -long stent length -acute MI PES (27%) -LM -bifurcation -vulnerable plaque study Reangiography 27% 40% SES: 1. 6% PES: 4. 1% SES: 3. 7% PES: 5. 4%
Why CYPHER is Superior 1. Late loss and restenosis in diabetic patients
Direct Comparison CYPHER vs TAXUS Late Loss – Overall Population In-Stent Late Loss @ 8 Months mm P=0. 02 P<0. 001 P=0. 007
Direct Comparison CYPHER vs TAXUS Late Loss – Diabetic Patients In-Stent Late Loss @ 8 Months P=0. 02 N=103 N=66 N=59 P<0. 001 mm P<0. 001 N=244 N=241
Direct Comparison CYPHER vs TAXUS Binary Restenosis – Overall Population Risk Ratio (95% CI) % Weight ISAR-DESIRE 0. 66 ( 0. 35, 1. 24) 9. 8 ISAR-DIABETES 0. 42 ( 0. 18, 0. 96) 6. 1 SIRTAX 0. 56 ( 0. 35, 0. 91) 15. 2 CORPAL 0. 67 ( 0. 41, 1. 09) 14. 8 REALITY 0. 86 ( 0. 65, 1. 14) 30. 6 ISAR-SMART 3 0. 60 ( 0. 36, 1. 00) 13. 8 Long DES II 0. 29 ( 0. 11, 0. 76) 4. 6 PROSIT 0. 43 ( 0. 17, 1. 10) 5. 0 Overall 0. 63 ( 0. 51, 0. 79), I 2=21. 3% 0. 04 0. 1 Favours SES 0. 5 1 2 Risk Ratio 10 25 Favours PES
Direct Comparison CYPHER vs TAXUS Binary Restenosis – Diabetic Patients In-Segment Restenosis @ 8 Months P=0. 11 P=0. 20 RR 15% N=66 N=59 N=244 N=242 N=412 N=404 % P=0. 02 N=103
Direct Comparison CYPHER vs TAXUS TLR – Overall Population Risk Ratio (95% CI) % Weight TAXI 2. 94 ( 0. 31, 27. 80) 1. 0 ISAR-DESIRE ISAR-DIABETES 0. 42 ( 0. 19, 0. 92) 0. 53 ( 0. 23, 1. 21) 7. 3 6. 6 SIRTAX 0. 55 ( 0. 36, 0. 86) 18. 3 CORPAL 0. 64 ( 0. 36, 1. 11) 12. 7 REALITY BASKET 0. 96 ( 0. 64, 1. 44) 0. 50 ( 0. 22, 1. 14) 20. 0 6. 6 ISAR-SMART 3 0. 43 ( 0. 23, 0. 80) 10. 8 Zhang et al 0. 73 ( 0. 36, 1. 45) 9. 0 Long DES II 0. 32 ( 0. 12, 0. 86) 4. 8 PROSIT Overall 0. 33 ( 0. 09, 1. 19) 2. 9 0. 59 ( 0. 47, 0. 74), I 2=16. 1% 0. 04 0. 1 Favours SES N=2901 0. 5 1 2 Risk Ratio 10 25 Favours PES N=2853
Direct Comparison CYPHER vs TAXUS TLR – Diabetic Patients Target Lesion Revascularization @ 12 Months P=0. 06 P=0. 30 RR 23% N=186 N=192 N=419 N=410 % P=0. 02 N=125 N=108 N=93
Individual Patient Data Meta-Analysis Risk of TLR and Diabetes Target Lesion Revascularization N Risk Ratio & 95% CI No Diabetes 1, 928 P=0. 006 I 2=0% 0. 60 (0. 42, 0. 86) Diabetes 887 P=0. 18 I 2=65% 0. 54 (0. 22, 1. 33) NIDDM 602 P=0. 39 I 2=0% 0. 78 (0. 43, 1. 38) Insulin dependent Diabetes Pooled 256 2, 786 P=0. 68 I 2=71% 0. 2 Favors SES 1 0. 61 (0. 06, 6. 46) 5 Favors PES Random Effects Model Data from ISAR-DESIRE, ISAR-DIABETES, REALITY, SIRTAX
Individual Patient Data Meta-Analysis Risk of TLR and NIDDM Target Lesion Revascularization N NIDDM Risk Ratio & 95% CI P=0. 39 I 2=0% 602 ISAR-DESIRE 0. 78 (0. 43, 1. 38) 0. 47 (0. 04, 5. 31) ISAR-DIABETES 0. 76 (0. 29, 1. 99) SIRTAX 0. 54 (0. 14, 2. 00) REALITY 1. 00 (0. 40, 2. 59) 0. 2 Favors SES 1 5 Favors PES Random Effects Model Data from ISAR-DESIRE, ISAR-DIABETES, REALITY, SIRTAX
Individual Patient Data Meta-Analysis Risk of TLR and IDDM Target Lesion Revascularization N IDDM Risk Ratio & 95% CI P=0. 68 I 2=71% 256 0. 61 (0. 06, 6. 46) P=0. 68, I 2=71% ISAR-DIABETES 0. 13 (0. 02, 1. 21) SIRTAX 0. 26 (0. 03, 2. 35) REALITY 6. 50 (0. 73, 58. 0) 0. 2 Favors SES 1 5 Favors PES Random Effects Model Data from ISAR-DESIRE, ISAR-DIABETES, REALITY, SIRTAX
Why CYPHER is Superior 1. Late loss and restenosis in diabetic patients 2. Vessel size in diabetic patients
Acute MI Elective PCI Woodfield SL et al. JACC 1996; 28: 1661 Mehran et al. JACC 2004; 43: 1348 P=0. 004 N=573 N=93 P=0. 007 P=0. 004 N=182 N=23 N=512 N=77 Reference Vessel Diameter (mm) Diabetes and Vessel Size P=0. 05 N=1200 N=235 N=204
Predictive Factors of Restenosis in the Drug-Eluting Stent Era Kastrati A et al. Circulation 2006; 113: 2293 -00 1845 patients 9. 2% TLR Vessel size ≥ 2. 6 mm Vessel size <2. 6 mm 7. 2% 11. 3% PES SES 7. 2% PES 7. 8% 15. 6%
SIRTAX – Subgroup Analysis of CYPHER vs TAXUS in Small Vessels (<2. 75 mm) RVD: 2. 45 mm; Mean lesion length: 12. 2 mm mm Late Loss P<0. 001 N=132 N=134 Restenosis % P=0. 001 N=132 N=134 TLR % P=0. 001 N=185
ISAR-SMART 3: Randomized Comparison of CYPHER vs TAXUS in Small Vessels (<2. 80 mm) Mehilli J et al. Eur Heart J 2006; 27: 260 -66 RVD: 2. 40 mm; Mean lesion length: 12. 3 mm mm Late Loss P<0. 001 N=176 N=174 Restenosis % P=0. 047 N=176 N=174 TLR % P=0. 008 N=180
Individual Patient Data Meta-Analysis Risk of TLR and Small Vessels
Why CYPHER is Superior 1. Late Loss and restenosis in diabetic patients 2. Vessel size in diabetic patients 3. Risk of stent thrombosis in diabetic patients
Diabetes as Predictor of Stent Thrombosis at One Year in The Era of Drug-Eluting Stents OR=2. 8 (1. 7 -4. 3) Kuchulakanti Circulation 2006 Urban Circulation 2006 HR=3. 7 (1. 7 -7. 9) HR=2. 3 (1. 3 -4. 0) Odds/Hazard Ratio OR=2. 0 (0. 8 -4. 9) Iakovou JAMA 2005 Bern-Rotterdam submitted
Direct Comparison CYPHER vs TAXUS Stent Thrombosis– Overall Population Risk Ratio (95% CI) % Weight TAXI 2. 94 ( 0. 12, 71. 37) 2. 9 ISAR-DIABETES 0. 33 ( 0. 01, 8. 10) 2. 9 SIRTAX 1. 12 ( 0. 46, 2. 74) 36. 5 CORPAL 4. 85 ( 0. 23, 100. 62) REALITY 0. 38 ( 0. 13, 1. 05) 27. 6 BASKET 1. 06 ( 0. 22, 5. 23) 11. 5 Zhang et al 0. 55 ( 0. 09, 3. 28) 9. 2 Long DES II 5. 15 ( 0. 25, 106. 59) 3. 2 PROSIT 0. 20 ( 0. 01, 4. 09) 3. 2 Overall 0. 80 ( 0. 47, 1. 37), I 2=0% 0. 04 0. 1 Favours SES 0. 5 1 2 Risk Ratio 10 25 Favours PES 3. 2
Direct Comparison CYPHER vs TAXUS Stent Thrombosis – Diabetic Patients Stent Thrombosis @ 9 -12 Months P=ns P=0. 28 % P=. 50 N=125 N=108 N=109 N=187 N=192
Direct Comparison CYPHER vs TAXUS Cardiac Mortality – Diabetic Patients Cardiac Death @ 9 -12 Months P=0. 34 % P=0. 52 N=125 N=108 N=93 N=187 N=192
Direct Comparison CYPHER vs TAXUS Myocardial Infarction – Diabetic Patients Myocardial Infarction @ 9 -12 Months P=0. 20 N=125 N=108 N=109 P=1. 00 % P=0. 72 N=187 N=192
CYPHER is Superior in Diabetics • Because CYPHER provides in diabetic patients – – – • Because CYPHER provides in patients with small vessels, which are more prevalent in diabetic patients – – – • Lower late loss A trend towards lower restenosis A trend towards lower target lesion revascularization Lower late loss Lower restenosis Lower target lesion revascularization Patients with IDDM require further study
How Can the Differences Between SIRTAX and REALITY Be Resolved? Morice MC et al. JAMA 2006; 295: 895 -904 Windecker S et al. N Engl J Med 2005; 353: 653 -62 No Diabetes RR=50% P=0. 11 RR=30% P=0. 06 Restenosis % RR=41% P=0. 06 Diabetes R=20% R P=0. 20
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