DES In-stent Restenosis

Transcription

1 DES In-stent Restenosis Roxana Mehran, MD Columbia University Medical Center The Cardiovascular Research Foundation

2 DES Restenosis Mechanisms Predictors Morphological patterns Therapy approach

3 Mechanisms of DES Restenosis Biological factors Drug resistance Hypersensitivity Mechanical factors Non uniform stent strut distribution Stent fractures Polymer peeling Non uniform drug deposition Technical factors Incomplete stent expansion Stent gaps or misses (uncovered lesion segments) Barotrauma to unstented segments

4 DES fractures a a Post Follow-up b Stent b c c Restenosis Aoki J. et al. CCI 27;69: 38-6

5 Stent Fracture Analysis Review of Adverse Event Reports submitted to Cordis between August 23 - July % In-stent restenosis 47.4 Follow-up findings P< mm 1 In-stent late loss.96 P<.1.17 Fracture SIRIUS Fracture SIRIUS N=38 N=35 N=38 N=35 Popma JJ. et al. DES revolution IV, 27

6 Technical factors Stent underexpansion

7 Technical factors Stent underexpansion Post-Procedure Procedure MSA and Binary Restenosis Cypher Minimum stent area (mm 2 ) (sensitivity and specificity curves) Taxus Minimum Stent Area (MSA, mm 2 ) Sonoda S. et al. J Am Coll Cardiol 24;43: Weissman N. TCT 26

8 Technical factors Gap Incomplete stent coverage Stent edge restenosis is frequently associated with local trauma outside the stent. In-stent restenosis occurs as a localized lesion, commonly associated with a discontinuity in stent coverage. Lemos A. et al. Circulation 23; 18: 257-6

9 DES Restenosis Mechanisms Predictors Morphological patterns Therapy approach

10 Independent predictors of TLR after DES implantation Randomized trials (on label) SES arm in SIRIUS Odds ratio Post procedure in-stent MLD.184 Total implanted stent length 1.27 PES arm in TAXUS IV Hazard ratio (95% CI) No study stents implanted 5.86 ( ) No prior MI 3.7 ( ) Female gender 2.33 (1.8 5.) Lesion length 1.5 ( )

11 Independent predictors of DES restenosis Registries (including off-label) Rotterdam (Circulation. 24) In-stent restenosis lesion Ostial lesions DM Vessel size LAD Munich (Circulation. 26) Vessel size Final Diameter stenosis DES type Seoul (Am J Cardiol. 26) DES type Final MLD Lesion length Washington (ACC. 27) Age Hypertension Procedural length Lack of IVUS guidance Total stented length Milan (AHA. 26) DM Unstable angina Reference vessel diameter Number of stents per lesion

12 DES Restenosis Mechanisms Predictors Morphological patterns Therapy approach «Delayed» restenosis

13 Morphological Patterns of DES In-Stent Restenosis Lesions SIRIUS I - focal Sirolimus (n=31) 87% Control (n=128) 42% P-value <.1 II/III diffuse or proliferative 6.5% 5% <.1 IV - total occlusion 6.5% 8%.895 TAXUS IV I - focal Paclitaxel (n=16) 63% Control (n=65) 31% P-value <.1 II/III diffuse or proliferative 24% 66% <.1 IV - total occlusion 13% 3%.245

14 Patterns of In-Stent Restenosis Milan Corbett SJ. et al. Eur Heart J 26 Cypher vs Taxus Taxus Cypher 11.3 N=149 N= Seoul Park CB. et al. AHA N=8 5.2 N= Focal Diffuse Proliferative Occlusive 76.3

15 Patterns of In-Stent Restenosis Milan experience Cypher, N=15 Number of leions P< P<.1 25 Taxus, N= Focal intra-stent Diffuse intra-stent Corbett SJ. et al. Eur Heart J 26 27:

16 DES Restenosis Mechanisms Predictors Morphological patterns Therapy approach

17 Conventional therapies vs SES for DES Failures 6-month angiographic outcomes % In-stent restenosis mm In-stent late loss 35 Conventional N=25 Cutting balloon 11 VBT 14 P=.6 4 SES N= Kim YH. et al. Am J Cardiol 26;98: Conventional N=25 Cutting balloon 11 VBT SES N=33 P=.21

18 SES vs PES for SES Failures Multicenter Registry in Asia 1 year 1 year % P< % 6.4 P< SES PES SES PES N=198 lesions N=161 lesions N=156 pts N=152 pts Nakamura S. et al. ACC 27

19 Same DES vs other DES vs. POBA for DES Failures Does the switch therapy work? % 1 year P= Same DES Other DES POBA N=37 pts N=62 pts N=19 pts Solinas E. et al. TCT 26

20 Same DES vs other DES vs. other treatment for DES Failures Does the switch therapy work? % Clinical 1 year P=.81 P= P=.62 P= Death Q-MI TVR MACE Same DES N=43 Different DES N=4 Garg S. et al. CCI. 27;7: 9-14

21 Same DES vs other DES vs other treatment for DES Failures Does the switch therapy work? 3 % In-stent mean 25.7 months mean 25.7 months P=1. % P= Same DES Different DES Same DES Different DES N=17 N=94 N=17 N=94 Cosgrave J. et al. AHJ.27;153: 354-9

22 Do patterns of in-stent restenosis predict outcomes in the DES era? QCA 9 months % 6 In-stent restenosis Late loss P=.1 mm P= Focal Non focal Focal Non focal N=11 N=47 N=11 N=47 Cosgrave J. et al. JACC 26;47:

23 Current therapeutic options according to potential mechanisms of DES restenosis Type of restenosis Focal in-stent Focal at stent edge Diffuse in-stent Proliferative Potential mechanisms Underexpansion Fracture Local vessel biology Heterogeneous drug distribution Geographic miss Plaque progression Vessel biology / Drug resistance Vessel biology / Drug resistance Treatment options BA DES, BA DES, BA, atherectomy DES, BA, atherectomy DES DES Different DES, CABG Different DES, CABG Costa MA. et al. AHJ.27;153: 447-9

24 DES Restenosis Summary Restenosis after DES still occurs and at a disturbing frequency in the highest risk lesion/patient subsets. Underlying mechanism of DES restenosis involve a complex interplay of biological, mechanical, and technical (operator-dependent) factors. Strut fractures are more frequent than previously suspected, occurring most commonly at the edge of an overlap segment and they have been implicated in many clinical events, including restenosis, thrombosis, and aneurysm formation.

25 DES Restenosis Summary The morphologic patterns of DES restenosis are different from BMS, favoring a more focal and easily treated pattern with expected improved clinical outcomes. The treatment of DES restenosis is based on appreciation of underlying mechanisms and can vary from simple POBA, to DES when appropriate, to CABG in the most extreme cases. Late DES restenosis remains an infrequent clinical event, despite the differing healing patterns relative to BMS.