HCS Working Group Seminars Macedonia Pallas Hotel, Friday 21 st February Drug-eluting stents Are they all equal?

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1 HCS Working Group Seminars Macedonia Pallas Hotel, Friday 21 st February 2014 Drug-eluting stents Are they all equal? Vassilis Spanos Interventional Cardiologist, As. Director 3 rd Cardiology Clinic Euroclinic Hospital, Athens

2 HCS Working Group Seminars Macedonia Pallas Hotel, Friday 21 st February 2014 Drug-eluting stents How do I choose between them? Vassilis Spanos Interventional Cardiologist, As. Director 3 rd Cardiology Clinic Euroclinic Hospital, Athens

3 Mechanisms of in-stent restenosis In-stent restenosis is the result of: Inappropriate stent expansion or Neointimal hyperplasia or both V Spanos et al. The challenge of in-stent restenosis: insights from intravascular ultrasound review article (Eur Heart J Jan;24(2): )

4 Sirolimus-eluting stent: overcoming restenosis Sousa JE et al. Lack of Neointimal Proliferation After Implantation of Sirolimus-Coated Stents in Human Coronary Arteries : A Quantitative Coronary Angiography and Three-Dimensional Intravascular Ultrasound Study ( Circulation. 2001;103: )

5 An unsuccessful trial - QuaDDS stent CONCLUSION: This single case report highlights the problem that late coronary thrombosis following paclitaxel eluting stent implantation may be an important limitation of restenosis prevention by some drug eluting stents. In the absence of other data, we think that combined antiplatelet treatment should be continued in the long term, unless it is contraindicated F. Liistro, A. Colombo: Late acute thrombosis after paclitaxel eluting stent implantation (Heart 2001;86: )

6 DES: a lot of different devices Efficacy Safety

7 DES: a lot of different devices Efficacy Late Lumen Loss Intimal Hyperplasia (IVUS) Restenosis Safety Complete endotthelization (OCT) Incomplete apposition (IVUS) Repeat Revascularization TVF (Death, CVA, MI) Stent thrombosis MI TVF (Death, CVA, TVR)

8 Late Lumen Loss with DES 0.31mm 0.09mm Ellis SG et al: Relationship between angiographic late loss and target lesion revascularization after coronary stent implantation: Analysis from the TAXUS-IV trial J Am Coll Cardiol. 2005;45(8):

9 Taxus vs. Cypher REALITY study MC. Morice et. al. Sirolimus- vs paclitaxel-eluting stents in de novo coronary artery lesions: the REALITY trial: a randomized controlled trial JAMA 2006: 295;

10 Taxus vs. Cypher: SIRTAX study CLINICAL FU only MACE at 9 months was 6.2% in the Cypher vs. 10.8% in the Taxus group (p=0.009) Difference driven by a lower rate of TLR (4.8% vs. 8.3%. p=0.03) Restenosis 6.6% vs. 11.7% (p=0.02) S. Windecker et.al. Sirolimus-eluting and paclitaxel-eluting stents for coronary revascularization N Engl J Med 2005;353:

11 Taxus vs. Cypher stent: small vessels Lesions in vessels<2.8mm received either Taxus stents (n=180) or Cypher (n=180) Taxus stents did not reach the non- inferiority margin of 0.16mm late lumen loss Restenosis rate was 19.0% (Taxus) vs. 11.4% (Cypher, p=0.047) TLR was 14.7% vs. 6.6% respectively (p=0.008) J. Mehilli et.al. Randomized trial of paclitaxel- and sirolimus-eluting stents in small coronary vessels Eur Heart J 2006;27:

12 Taxus vs. Cypher: ISAR-DIABETES 250 pts with DM randomly assigned to receive Taxus or Cypher stents In-segment late luminal loss was 0.24mm greater in the Taxus stent group (p=0.002) In-segment restenosis rate was 16.5% for Taxus vs. 6.9% for Cypher group (p=0.03) TLR rate was 12.0% for Taxus vs. 6.4% for Cypher group (p=0.13). A. Dibra et.al. Paclitaxel-eluting or sirolimus-eluting stents to prevent restenosis in diabetic patients N Engl J Med 2005;353:

13 DES: a lot of different devices Efficacy Late Lumen Loss Intimal Hyperplasia (IVUS) Restenosis Safety Complete endotthelization (OCT) Incomplete apposition (IVUS) Repeat Revascularization TVF (Death, CVA, MI) Stent thrombosis MI TVF (Death, CVA, TVR)

14 Offsetting impact of ST and restenosis on the occurrence of death/mi G. Stone et.al. Offsetting impact of thrombosis and restenosis on the occurrence of death and myocardial infarction after paclitaxel-eluting and bare metal stent implantation Circulation 2007 Jun 5;115(22):2842-7

15 Late stent thrombosis E. McFadden et al. Late thrombosis in DES after discontinuation of antiplatelet therapy Lancet.2004; 364:

16 DES: a lot of different devices Efficacy Late Lumen Loss Intimal Hyperplasia (IVUS) Restenosis Safety Complete endotthelization (OCT) Incomplete apposition (IVUS) Repeat Revascularization TVF (Death, CVA, MI) Stent thrombosis MI TVF (Death, CVA, TVR)

17 Sirolimus-eluting stent: overcoming restenosis Sousa JE et al. Lack of Neointimal Proliferation After Implantation of Sirolimus-Coated Stents in Human Coronary Arteries : A Quantitative Coronary Angiography and Three-Dimensional Intravascular Ultrasound Study ( Circulation. 2001;103: )

18 Taxus vs. Cypher REALITY study More stent thromboses with Taxus (13, 1.9%) than Cypher (5, 0.7%), although the difference did not reach statistical significance MC. Morice et. al. Sirolimus- vs paclitaxel-eluting stents in de novo coronary artery lesions: the REALITY trial: a randomized controlled trial JAMA 2006: 295;

19 DES: a lot of different devices Efficacy Late Lumen Loss Intimal Hyperplasia (IVUS) Restenosis Safety Complete endotthelization (OCT) Incomplete apposition (IVUS) Repeat Revascularization TVF (Death, CVA, MI) Stent thrombosis MI TVF (Death, CVA, TVR)

20 Incomplete strut coverage in Late ST Ko et al Davlouros et al Miyazaki et al Guagliumi et al Alfonso et al n 18 DES 7 DES 6 DES 18 DES 8 BMS/ 7 DES DES type 14 SES/ 3 PES/ 1 EES Interval (months) Uncovered struts Patients with uncovered struts N/A 5SES/ 1PES 6 SES/ 10 PES/ 1 EES/ 1 ZES N/A 40±20 8 (3-62) 37±12 21 (6-60) 43±51-32% 29% 12.3% - 50% 100% 100% 83.3% 60% Ko et al, Int J Cardiovasc Img 2012, Davlouros et al, Circ J 2011, Miyazaki et al, Circ J 2012, Guagliumi et al, JACC Intv 2012, Anfonso et al, Heart 2012

21 DES coverage by OCT Papayannis AC et al, CCI 2012, Gutierrez-Chico JL et al, EHJ CI 2012

22 DES coverage by OCT: Discrepancy between differences in coverage and clinical outcome

23 DES: a lot of different devices Efficacy Late Lumen Loss Intimal Hyperplasia (IVUS) Restenosis Safety Complete endotthelization (OCT) Incomplete apposition (IVUS) Repeat Revascularization TVF (Death, CVA, MI) Stent thrombosis MI TVF (Death, CVA, TVR)

24 DES: a lot of different devices DES proven superior to BMS and used extensively in everyday practice in USA & Europe Cypher stent Taxus stent DES tested in clinical studies and/or used in everyday practice in Europe DES proven superior to BMS DES proven non-inferior to either Cypher or Taxus

25 The Endeavor stent: ENDEAVOR II Study TVF at 9 months was reduced from 15.1% to 7.9% with the Endeavor (p=0.0001) The rate of in-segment restenosis was reduced from 35.0% to 13.2% with Endeavor (p<0.0001) Fajadet J. et.al. Randomized, double-blind, blind, multicenter study of the Endeavor zotarolimus-eluting phosphorylcholine-encapsulated encapsulated stent for treatment of native coronary artery lesions: clinical and angiographic results of the ENDEAVOR II trial Circulation 2006; 114:

26 The Endeavor stent: ENDEAVOR III Study End points Endeavor (n=282) Cypher (n=94) In-stent mean lumen diameter (mm) <0.001 In-segment mean lumen diameter (mm) <0.001 In-stent diameter stenosis (%) <0.001 In-segment diameter stenosis (%) <0.001 In-stent binary restenosis (%) In-segment binary restenosis (%) In-stent late loss (mm) <0.001 In-segment late loss (mm) <0.001 Kandzari D. et.al. Comparison of zotarolimus-eluting and sirolimus-eluting stents in patients with native coronary artery disease: a randomized controlled trial JACC 2006; 46: p

27 Late Lumen Loss with DES 0.60mm 0.15mm Ellis SG et al: Relationship between angiographic late loss and target lesion revascularization after coronary stent implantation: Analysis from the TAXUS-IV trial J Am Coll Cardiol. 2005;45(8):

28 The Endeavor stent: SORT OUT III Study End points Endeavor (n=1162) Cypher (n=1170) p MACE (Cardiac death, MI, TVR) 113 (10.0%) 53 (5.0%) < TLR 71 (6.0%) 20 (2.0%) < All cause mortality 51 (4.0%) 32 (3.0%) Rasmunsen K. et.al. Efficacy and safety of zotarolimus-eluting and sirolimus-eluting coronary stents in routine clinical care (SORT OUT III): a randomised controlled superiority trial JACC 2006; 46:

29 Biolimus vs Sirolimus eluting stents 5 years follow up of the LEADERS Trial 857 pts with BES vs. 850 with SES P. Serruys, TCT 2012

30 Biolimus vs Sirolimus eluting stents 5 years follow up of the LEADERS Trial 857 pts with BES vs. 850 with SES P. Serruys, TCT 2012

31 Biolimus vs Sirolimus eluting stents 5 years follow up of the LEADERS Trial 857 pts with BES vs. 850 with SES P. Serruys, TCT 2012

32 DES: Different approaches

33 Αντίδραση υπερευαισθησίας J. Nebeker et al. (JACC. 2006;47: )

34 Paclitaxel vs. Everolimus eluting stents 2 years follow up of the SPIRIT IV Trial 2458 pts with EES vs with PES Stone G. et al 2 year follow up from the SPIRIT IV Trial J Am Coll Cardiol 2011:28;58(1):19-25

35 EES vs. SES: SORT OUT IV Trial 1390 pts (1805 lesions) with EES vs. 1384pts (1779 lesions) with SES Jensen L. et al Circulation.2012; 125:

36 Less ST with Everolimus eluting stents 4 years Registry, pts: 4212 lsns EES PES SES Lower risk of cardiac death/mi with EES compared with PES (hazard ratio:0.65; 95% confidence interval, ; 0.75; P<0.0001) Raber L. et al Very Late Coronary Stent Thrombosis of a Newer-Generation Everolimus-Eluting Stent Compared With Early-Generation Drug-Eluting Stents Circulation.2012; 125:

37 ZES Resolute vs. EES 13 months follow up of the RESOLUTE All ComersTrial 1140 pts with ZES vs with EES 0.15mm 0.06mm Serruys P. et al Comparison of Zotarolimus-Eluting and Everolimus-Eluting Coronary Stents N Engl J Med 2010; 363:

38 New DES have to present convincing data S. Windecker et al. (PCR 2013)

39 The CoStar stent: PISCES Study Lowest in-stent late loss (0.38 mm, and 0.30 mm, p <0.01) and volume obstruction (8% and 5%, p <0.01) in the 30-day release groups (10µg, 30µg). 8.6% MACE for DES: death 0.5%, myocardial infarction 2.7%, and TLR 5.3%. P. Serruys et al. ( JACC 2005;46: )

40 CONCLUSIONS DES are complex devices with different characteristics and should be judged from their results as regards efficacy and safety There are second generation DES that have shown superiority compared to first generation (Cypher or Taxus) stents DES technology will continue to evolve aiming to devices with higher efficacy and safety

41 Thank you for your attention!

42 The Endeavor stent: More safe? 1 year follow up of the ZEST Trial 2645 pts randomized to ZES, SES, PES ZES SES PES Park D. et.al. Comparison of Zotarolimus-Eluting Stents With Sirolimus- and Paclitaxel-Eluting Stents for Coronary Revascularization : The ZEST (Comparison of the Efficacy and Safety of Zotarolimus-Eluting Stent with Sirolimus-Eluting and PacliTaxel-Eluting Stent for Coronary Lesions) Randomized Trial JACC 2010; 56:

43 An unsuccessful trial: SCORE QuaDDS stent 7,4% restenosis rate (32,7%), but 10,3% stent thrombosis (0,7%) E. Grube et al. ( JACC 2004;44: )

44 Loss of side branches after Taxus stent implantation G. Stone, TCT 2005

45 2 years follow up of the COMPARE Trial 897pts (1286 lesions) with EES vs. 903pts (1294 lsns) with PES Smits P. et al 2 year follow up of a Randomized Controlled Trial of EES and PES for Coronary Revascularization in Daily Practice J Am Coll Cardiol. 2011;58(1):11-18

46 Paclitaxel vs. Everolimus eluting stents 2 years follow up of the SPIRIT III Trial 669 lesions with EES vs. 333 with PES 0.28mm 0.14mm Treatment with Everolimus stent resulted in a trend toward fewer re- interventions (TLR), fewer MIs and reduction in the composite of death/mi (4.8% vs. 8.1%, relative risk: 0.60, 95% CI: 0.36 to 0.99, p=0.055) Stone G. et al Randomized Comparison of Everolimus-Eluting Eluting and Paclitaxel-Eluting Stents.. Circulation. 2009;119:

47 Offsetting impact of ST and restenosis on the occurrence of death/mi G. Stone et.al. Offsetting impact of thrombosis and restenosis on the occurrence of death and myocardial infarction after paclitaxel-eluting and bare metal stent implantation Circulation 2007 Jun 5;115(22):2842-7

48 Offsetting impact of ST and restenosis on the occurrence of death/mi G. Stone et.al. Offsetting impact of thrombosis and restenosis on the occurrence of death and myocardial infarction after paclitaxel-eluting and bare metal stent implantation Circulation 2007 Jun 5;115(22):2842-7

49 Taxus vs. Cypher REALITY study MC. Morice et. al. Sirolimus- vs paclitaxel-eluting stents in de novo coronary artery lesions: the REALITY trial: a randomized controlled trial JAMA 2006: 295;

50 DES: a lot of different devices Manufacturer Name Drug Stent material Polymer Status Abbott ZoMaxx Zotarolimus Tantalum/St steel Durable Sorin Janus Tacrolimus Stainless steel None CE Conor CoStar Paclitaxel Cobalt chromium Bioabsorbable CE Guidant Medtronic Xience V Endeavor Everolimus Cobalt chromium Durable CE Zotarolimus Cobalt chromium Durable CE Terumo Nobori Biolimus-A9 Stainless steel Bioabsorbable

51 The bioabsorbable stent: ABSORB Study 6-month follow-up 26 lesions In-stent diameter stenosis (%) 27 In-stent late loss (mm) 0.44 In-stent restenosis (%) 11.5 A stent made from a polylactic acid (PLA) backbone, with an everolimus/pla coating expected to dissolve completely after months Late loss and restenosis were greater than with current DES, probably due to the 15% shrinkage seen with the new stent Serruys P. American College of Cardiology 2007 Scientific Sessions; March 24, 2007.

52 DES: a lot of different devices DES proven superior to BMS and used extensively in everyday practice in USA & Europe Cypher stent Taxus stent DES tested in clinical studies and/or used in everyday practice in Europe DES proven superior to BMS DES proven non-inferior to either Cypher or Taxus

53 Taxus vs. Cypher stent: long lesions Lesions 24mm treated with long Cypher (223), Taxus (194), or BM stents Mean Lesion length treated with Cypher stent: 36.0 ± 14.9mm Mean Lesion length treated with Taxus stent: 36.3 ± 14.5mm 6 month in-segment restenosis rates were higher for Taxus (21.3%) than Cypher group (9.3%, p=0.002) 6 month MACE rate was similar: 13.0% for Cypher and 15.7% for Taxus stent Y. Kim et.al. Comparison of sirolimus-eluting stent, paclitaxel-eluting stent, and bare metal stent in the treatment of long coronary lesions Cath Cardiovasc Interv 2006;67(2):

54 The Xience V stent: SPIRIT III Study End point XIENCE V Taxus P In-segment late loss (mm) <0.001 (noninferiority) (superiority) In-stent late loss (mm) In-segment binary restenosis (%) Target vessel failure < (noninferiority) MACE (superiority) Stone G. American College of Cardiology 2007 Scientific Sessions. March 24, 2007

55 PES vs. SES: REALITY study MC. Morice. April tctmd.com