1 / 25

DES: this house believes that late loss is an important factor in the choice of DES

DES: this house believes that late loss is an important factor in the choice of DES. Angela Hoye Castle Hill Hospital, Hull. No conflicts of interest. What is late loss?. ?. What is late loss?. What is late lumen loss?.

lali
Download Presentation

DES: this house believes that late loss is an important factor in the choice of DES

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. DES: this house believes that late loss is an important factor in the choice of DES Angela Hoye Castle Hill Hospital, Hull No conflicts of interest

  2. What is late loss? ?

  3. What is late loss?

  4. What is late lumen loss? Difference in minimal lumen diameter (MLD) at the end of the procedure following stent implantation, minus the MLD on follow-up angiography - same angulation - after IC nitrate

  5. Example of in-stent restenosis in a bare metal stent

  6. MLD 2.72mm MLD 1.68mm Late loss: 2.72-1.60 = 1.04 mm

  7. Late loss • The therapeutic objective of using a drug-eluting stent is to minimize the need for repeat target lesion revascularisation (TLR) by preventing neointimal hyperplasia • Late loss represents a measure of the biological response following stent implantation (suppression of neointimal hyperplasia) • Late loss is a direct angiographic measure of the absolute amount of re-narrowing

  8. Late loss • Late loss is independent of reference vessel diameter • In clinical practice, small differences in late loss and restenosis will be amplified according to the risk profile of the target patient population

  9. Stent performance compared with lesion complexity Randomized trials Registries “Real world” Differences in late outcomes became apparent Stents appear similar Failure Rate Lesion complexity Edelman and Rogers, Circulation 1999;100:896-898

  10. Headroom >50%diameter stenosis - TLR Low Late Loss Stent Systems Conserve “Headroom” Late loss Late loss “headroom” is the space of extra late loss available for higher risk cohorts - headroom greatest for low in-stent late loss stent systems

  11. Differences between stents as a function of late loss distribution 24 Probability of TLR 20 16 Patients (%) 12 8 4 0 1.5 0.1 0.3 0.5 0.7 0.9 1.1 1.3 1.7 1.9 2.9 3.1 2.1 2.3 2.5 2.7 -1.3 -1.1 -0.9 -0.7 -0.5 -0.3 -0.1 Late loss (mm) Pocock TCT 2005

  12. Mean late loss = 0.2 mm 0.4 mm 1.0 mm DES with high late loss BMS DES with low late loss Differences between stents as a function of late loss distribution 24 Probability of TLR 20 16 Patients (%) The right tail end of the distribution impacts upon clinical outcomes 12 8 4 0 1.5 0.1 0.3 0.5 0.7 0.9 1.1 1.3 1.7 1.9 2.9 3.1 2.1 2.3 2.5 2.7 -1.3 -1.1 -0.9 -0.7 -0.5 -0.3 -0.1 Late loss (mm)

  13. 0.4 mm DES with high late loss BMS DES with low late loss • Vessel diameter is strongly predictive of increased TLR • In small vessels, even slight differences in late loss will be important Differences between stents as a function of late loss distribution 24 Mean late loss = 0.2 mm Probability of TLR 20 16 1.0 mm Patients (%) 12 8 4 0 1.5 0.1 0.3 0.5 0.7 0.9 1.1 1.3 1.7 1.9 2.9 3.1 2.1 2.3 2.5 2.7 -1.3 -1.1 -0.9 -0.7 -0.5 -0.3 -0.1 Late loss (mm)

  14. Mean late loss = 0.2 mm 0.4 mm DES with high late loss BMS DES with low late loss • Complex lesions increase late loss Differences between stents as a function of late loss distribution 24 Probability of TLR 20 16 1.0 mm Patients (%) 12 8 4 0 1.5 0.1 0.3 0.5 0.7 0.9 1.1 1.3 1.7 1.9 2.9 3.1 2.1 2.3 2.5 2.7 -1.3 -1.1 -0.9 -0.7 -0.5 -0.3 -0.1 Late loss (mm)

  15. In-stent late loss in DES trials (non-comparative studies) 1.0 0.8 0.62 0.61 0.6 (mm) 0.39 0.39 0.4 0.31 0.18 0.18 0.17 0.2 0.0 0 CYPHER TAXUS ENDEAVOR RAVEL1 SIRIUS2 NEW DIRECT4II5 IV6 VI7 I8 II9 SIRIUS3 5. Colombo A. TCT 2002 6. Stone G. et al. N Engl J Med 2004; 350:221-231 7. Dawkins K. EuroPCR 2004 1. Morice M.C. et al. N Engl J Med 2002;346:1773-80 2. Moses J. et al. N Engl J Med 2003;349:1315-23 3. Schofer J. ACC 2004 4. Moses J. ACC 2004 8. Meredith I. ACC 2004 9. Wijns W. ACC 2005

  16. Increasing complexity Head-to-Head Studies: relative complexity of populations (risk of restenosis) 1: Goy JACC 2005;45(2) 2: Kandzari TCT 2005 3: Morice ACC 2005 4: Windecker ACC 2005 5: Dibra NEJM 2005;353 6: Mehilli EHJ 2006;27

  17. ENDEAVOR III (8m) REALITY (8m) SIRTAX (9m) ISAR- DIABETES (6m) ISAR- SMART 3 (6m) 1.0 0.8 In-stent late loss (mm) 0.60 0.56 0.6 0.46 0.4 0.31 0.25 0.25 0.19 0.2 0.15 0.13 0.09 0 Increasing Level of Complexity of Study Populations Randomized DES Head-to-Head Studies: Differences in Mean Late Loss CYPHER TAXUS ENDEAVOR p<0.001 <0.001 <0.001 <0.001 <0.001

  18. LL 0.56 mm LL 0.45 mm 15.0 13.6 LL 0.31 mm LL 0.25 mm 8.3 8.0 7.6 LL 0.25 mm 7.0 LL 0.19 mm LL 0.13 mm 4.9 3.2 LL 0.09 mm Increasing Level of Complexity Randomized Head-to-Head Studies Illustrate a Trend Between Lower Late Loss and Lower Restenosis ISAR- DIABETES (6m) ISAR-SMART 3 (6m) REALITY1 (8m) SIRTAX (9m) p = ns 0.013 0.03 0.04 25 TAXUS 20 CYPHER 15 In Stent Restenosis Rate (%) 10 5 0

  19. LL 0.56 mm LL 0.45 mm 14.7 LL 0.25 mm 6.6 LL 0.31 mm 12.0 8.3 5.4 6.4 5.0 LL 0.25 mm 4.8 3.0 LL 0.19 mm LL 0.13 mm 1.0 LL 0.09 mm Increasing Level of Complexity Head-to-Head Studies Show Increased Divergence in Clinical Outcomes (TLR) as Complexity Increases ISAR- DIABETES (9m) ISAR- SMART 3 (9m) TAXi (7m) REALITY (8m) SIRTAX (9m) p = ns ns 0.025 0.13 0.02 20 TAXUS 15 CYPHER TLR (%) 10 5 0

  20. In Higher Risk Cohorts, Differences in Late Loss are More Strongly Associated with Risk of TLR 20 CYPHER 18 TAXUS ENDEAVOR 16 14 ISAR-SMART 3 Target Lesion Revascularization (%) 12 10 ISAR-DIABETES 8 SIRTAX 6 REALITY CORPAL 4 ENDEAVOR III 2 0 0.0 0.2 0.4 0.6 0.8 In-lesion Late Loss (mm) Adapted from Moliterno DJ. NEJM 2005; 353: 724-727

  21. Safety issues • Kastrati et al meta-analysis of CORPAL, ISAR-DESIRE, ISAR-DIABETES, REALITY, SIRTAX, and TAXi • n=3669 pts, SES versus PES • Death 1.4% for SES versus 1.6% for PES OR 0.85 (95% CI 0.50-1.46), p=0.56 • Death or AMI 4.9% for SES versus 5.8% for PES OR 0.84 (95% CI 0.63-1.12), p=0.23 • Stent thrombosis 0.9% for SES versus 1.1% for PES OR 85 (95% CI 0.46-1.59), p=0.62 • TLR favoured SES 5.1% for SES versus 7.8% for PES OR 64 (95% CI 0.49-0.84), p=0.001 Kastrati et al JAMA 2005 294:7

  22. Conclusions • The primary role of DES is to reduce the need for TLR whilst maintaining clinical safety • There is no evidence for any difference in terms of clinical safety with the currently available DESs • Lower late loss results in increased clinical benefit

  23. Conclusions • The increased “headroom” provided by lower late loss confers particular benefits in high-risk patients with diabetes and more complex lesions • There is good evidence against the notion of a late loss “threshold” below which all DES are inter-exchangeable – lower late loss is better

  24. Late loss is an important factor in the choice of DES

  25. Differences in drug elution CYPHER1 Slowly elutes over 90 days; 80% eluted at 30 days, complete at 90 days CYPHER ENDEAVOR 100 80 60 TAXUS2 Bimodal release of 10% of the drug, completed in 2 weeks, 90% sequestered on stent Drug Release (%) 40 20 TAXUS ENDEAVOR3 Nearly 100% of the drug elutes in the first 7 days and complete at 12 days 0 30 60 90 0 Thrombosis Inflammation Proliferation Extracellular matrix formation Days 1. Adapted from Nikol et al. Atherosclerosis 1996; 123: 17-31. 2. Stone G. Presented at ACC 2004.3. Ormiston J. Endeavor I Study presented at AHA 2004

More Related