Do we still need Bare Metal Stent? T. Santoso, M.D., Ph.D Medistra Hospital Univ. of Indonesia Medical School Jakarta, Indonesia

Transcription

1 Do we still need Bare Metal Stent? T. Santoso, M.D., Ph.D Medistra Hospital Univ. of Indonesia Medical School Jakarta, Indonesia

2 Presentation outline 1. What has the evidence-based medicine taught us about DES? - Cypher : 12,129 patients, 15 randomized studies - Taxus : 4,084 patients 2. Are DES so perfect that we always have to use them instead of Bare Metal Stent (BMS)?

3 1. What has the evidence based medicine taught us about DES? DES are safe DES are effective The beneficial effects of DES are durable

4 Cypher TM & Taxus TM Stent Thrombosis Stent Thrombosis (%) 2 1 N = 111,533 patients Acceptable zone (1-2%) RCTs e-cypher Rotterdam Milan Lenox Hill US TAXUS II TAXUS IV N=878 N=6,500 N=510 N=1112 N=101,000 N=536 N=662

5 IVUS: Late Incomplete Apposition % Frequency of Late Malapposition in Bare Metal Arm in DES Trials 9% 9% 6 4 4% 5% 4.4% 2 0 ACTION Control TAXUS II Real World Control Control TAXUS II SIRIUS Active Cypher No Clinical Events Attributed to Late Incomplete Apposition

6 SIRIUS : Angio Aneurysm at f/up The Two Worst SIRIUS Cases with Aneurysms at 8 mos angio f/up Both in Control Bare Metal Stents!!

7 1. What has the evidence based medicine taught us about DES? DES are safe DES are effective The beneficial effects of DES are durable

8 Drug Eluting Stent Trials Comparison of In-stent Late Loss BMS ASPECT TAXUS II TAXUS I TAXUS IV SIRIUS FUTURE RAVEL Low High SR MR F1 F2

9 Drug Eluting Stent Trials Comparison of % Volume Obstruction % BMS ASPECT TAXUS II TAXUS I SIRIUS FUTURE RAVEL Low High SR MR F1 F2

10 SIRIUS vs New Sirius vs TAXUS IV mm Late Loss (In-Segment) % Restenosis (In-Segment) % 79% 62% 75% 88% 70% SIRIUS New SIRIUS TAXUS IV SIRIUS New SIRIUS TAXUS IV Treatment Control

11 SIRIUS vs New Sirius vs TAXUS IV % TLR (@ 9 mos) % TVR (@ 9 mos) 75% 80% 73% 67% 78% 61% SIRIUS New SIRIUS TAXUS IV SIRIUS New SIRIUS TAXUS IV Treatment Control

12 SIRIUS - TLR Events Sirolimus Control Overall Male Female Diabetes No diabetes LAD Non-LAD Small vessel* Large vessel Short lesion Long lesion # Overlap No overlap % benefit across ALL lesion & patient subsets p-value #events prevented per 1000 pts *< 2.75 mm # >13.5 mm Hazard Ratio CI 95% Sirolimus better

13 New SIRIUS - TLR Events Odds ratios by Subgroup (9 mos) Sirolimus Control Overall Diabetes No diabetes LAD Non-LAD Small vessel* Large vessel Short lesion Long lesion # Overlap No overlap p-value < < Odds Ratiio, 95% CI #events prevented per 1000 pts

14 TAXUS 4 : TLR at 12 months All Non-diabetes DM, oral meds DM, insulin LAD Non-LAD RVD <2.5 mm RVD > mm RVD > 3.0 mm Lsn length <10 mm Lsn length mm Lsn length >20 mm RR TAXUS Control % 14.7% < % 13.1% < % 21.1% % 16.7% % 16.0% % 13.6% < % 20.1% < % 12.9% % 10.8% % 12.8% % 13.8% % 21.6% RR (95% CI) P

15 RESEARCH : TVR at 12 months Male Female Stable angina Acute coronary syndr. SVD MVD Diabetes mellitus No diabetes mellitus Short ls (stent length <33mm) Long ls (stent length >33mm) 33mm) Large vessel (>2.5 mm) Small vessel (<2.5mm)( 2.5mm) Bifurcation stenting No bifurcation stenting LAD Non-LAD No post-dilatation Post-dil. w/ 0.5 mm larger balloon Lemos PS, cs. Circulation 2004;109; Hazard Ratio HR 95% CI p-value < < < < <

16 SIRIUS : EFS Curves Survival Free From TLR Non-DM DM

17 SIRIUS : Diabetic Subgroup In-Segment Restenosis & TLR (@ 12 mos) % Restenosis TLR Restenosis TLR Restenosis TLR Overall Cypher Oral agents Insulin Bare metal stent

18 TAXUS 4: Diabetic Subgroup In-Segment Restenosis Restenosis % Control (n=267) P< No DM 29.7 TAXUS (n=291) P= N=209 n=209 n=213 n=37 n=52 n=21 DM oral agents P= n=26 DM Insulin

19 NewSIRIUS vs. TAXUS IV: Diabetics Restenosis (In-Segment) % p< % p< % 81% 34.5% 10.8% 6.4% New SIRIUS (n=95) TAXUS IV (n=136) CYPHER stent / TAXUS stent Control

20 1. What has the evidence based medicine taught us about DES? DES are safe DES are effective The beneficial effects of DES are durable

21 Angiographic FU with Cypher TM Stent FIM Trial Courtesy of A. Abizaid, MD

22 SIRIUS : Event Free Survival at 2 yrs For TLR, MACE, & TVF

23 TAXUS : Freedom from TLR

24 2. Are DES so perfect that we always have to use them instead of BMS? There is still no proof that DES reduce death or myocardial infarction Further studies required for certain indications Issue of cost Issue of late catch-up phenomenon Case examples

25 Occulo-stenotic Effect Event free survival BENESTENT II: 6 month angio RAVEL: 6 month angio Ruygrok P, cs. JACC 1999;34: RAVEL, NEJM 2002;346:

26 MACE vs. MICE MACE: Major Adverse Cardiac Events MICE : Minor Inconvenient Cardiac Events MICE Death Myocardial infarction ER CABG Subacute thrombosis Stroke Perforation Renal failure Vascular surgery MACE Restenosis Silent CK release Groin hematoma Modified after O Neill W, ACC 2004

27 SIRIUS: RBE* Events Cypher better Bare stent better P-value Overall Male Female Diabetes No Diabetes LAD Non-LAD Small vessel (<2.5) Large vessel Short lesion Long lesion (>13.5) Overlap No overlap Hazards Ratio 95% CI NS NS NS NS NS NS NS NS NS NS NS NS NS *Really Bad Events (death, MI, ER CABG) O Neill W, ACC 2004

28 TAXUS IV 9 Month Clinical Results Control Taxus (n=652) (n=662) p value Cardiac death 1.1% 1.4% ns MI 3.7% 3.5% ns Thrombosis (SAT) 0.8% 0.6% ns TLR 11.3% 3.0% <.0001 TVR 12.0% 4.7% <.0001 MACE 15.0% 8.5% =.0002

29 RESEARCH: One-year Adverse Events Cumulative risk of death, MI, or TLR Cumulative risk of clinically driven TVR Pre-SES Pre-SES SES SES Lemos PS, cs. Circulation 2004;109;190-5

30 RESEARCH: One-year death &/or MI No difference between DES & BMS!!! Cumulative risk of death Cumulative risk of death or MI Pre-SES SES Pre-SES SES Lemos PS, cs. Circulation 2004;109;190-5

31 2. Are DES so perfect that we always have to use them instead of BMS? There is still no proof that DES reduce death or myocardial infarction Further studies required for certain indications Issue of cost Issue of late catch-up phenomenon Case examples

32 DES Guidelines 2003 Class Condition I 1. Lesions of mm in length & mm in diameter, with 50% - 90% obstruction preprocedure* 2. Diabetes** 3. Lesions < 15 mm in length & mm in diameter** IIa IIb III 1. Ostial RCA, LAD, LCX, or protected LM lesions*** 2. Parent vessel bifurcatiob lesion with PTCA of SB 1. Recanalized CTO 2. Lesions > 30 mm in length & mm in diameter 3. In-stent restenosis focal pattern 1. SVG disease 2. In-stent restenosis diffuse pattern 3. Unprotected LM disease * Level of evidence A, entry criteria for SIRIUS, RAVEL & TAXUS II trials ** Level of Evidence B *** Registry data from DELIVER II & the SIRIUS studies (2003) O Neill W, Leon MB, Circulation 2003;107:

33 DES Guidelines 2004 Constantly changing landscape With so much new data being generated in the field of DES the guidelines (to be relevant) would have to be revised & modified literally every month Leon MB, ACC 2004

34 DES Guidelines 2004 Not fully justified?? Bifurcations Parent vessel only? Technique Need for branch vessel stent Acute MI & thrombus laden artery Safety, safety, safety!! SVG disease Unprotected LM disease Instent restenosis Larger stents Technique, regional vs. focal Rx Larger stents Technique Results in LM bifurcation Safety & efficacy in ultra-diffuse lesion & s/p brachytherapy

35 Bare Metal Stent Native vessel : Vessel > 3.5 mm Short lesion < 10 mm No diabetes mellitus SVG disease AMI? Others

36 Morphology Patterns of In-Segment Restenosis SIRIUS Morphology Patterns of Sirolimus (n=31) Control (n=128) p value I - Focal 87.0% (27) 42.2% (54) <0.001 II / III - Diffuse or 6.5% (2) 50.0% (64) <0.001 Proliferative IV - Total occlusion 6.5% (2) 7.8% (18) and focal ISR lesions are easy to treat

37 RESEARCH: Univariate OR of Binary Angiographic In-segment Restenosis Age (by decades) Female Diabetes NIDDM IDDM Current smoking Previous CABG AMI Stable angina Abxicimab LAD LCX RCA LM Graft Thrombus Type B2/C Instent restenosis Moderate/severe calcification Bifurcation (main vessel) Bifurcation (side branch) Ostial location CTO (> 3 mo) Number of stents Overlapping stents Stent diameter 2.25 mm Stented length (10 mm units) Stent length > 36 mm Lesion length Reference diameter MLD pre Diameter stenosis pre (10% units) MLD post Diametere stenosis post (10% units) OR 95% CI p < < < < < < < < < Lemos PS, cs. Circulation 2004;109;

38 RESEARCH: Multivariate Predictors & Actual Rates of Post-SES In-Segment Restenosis OR 95% CI p Rx of in-stent restenosis < Ostial location < Diabetes mellitus Total stent length* < Ref.diameter # Non-LAD < In-segment restenosis rate (%) * > 26 mm, higher tercile # < 2.17 mm, lower tercile Lemos PS, cs. Circulation 2004;109;

39 2. Are DES so perfect that we always have to use them instead of BMS? There is still no proof that DES reduce death or myocardial infarction Further studies required for certain indications Issue of cost Issue of late catch-up phenomenon Case examples

40 The Issue of Cost : Will DES Bankrupt Hospitals?

41 MACE vs. MICE MACE: Major Adverse Cardiac Events MICE : Minor Inconvenient Cardiac Events Cost Effective Lives Saved MICE MACE

42 Breakeven Analysis - MEDICARE O Neill W, ACC 2004

43

44 Is DES therapy always justified in all pts??? This could be serious!!. His body accepted the DES, his mind rejected the bill

45 Case 1: BMS vs. DES in a very tortuous, calcified vessel Angiogram: Case: post CABG, unprotected LM & 3VD LM:60% bifurc. stenosis, LAD:very tortuous, calcified with 90% stenosis midsegment, 80% stenosis distal LCX:100% block midsegment, RCA:100% block proximal, Gr. III coll fr. LAD-RCA SVG-RCA:100% block proximal, SVG-LCX:patent, No graft to LAD

46 Case 1: BMS vs. DES in a very tortuous, calcified vessel Angiogram: LM:60% bifurc. stenosis, LAD:very tortuous, calcified with 90% stenosis midsegment, 80% stenosis distal LCX:100% block midsegment, RCA:100% block proximal, Gr. III coll fr. LAD-RCA SVG-RCA:100% block proximal, SVG-LCX:patent, No graft to LAD

47 Case 1: BMS vs. DES in a very tortuous, calcified vessel Angiogram: LM:60% bifurc. stenosis, LAD:very tortuous, calcified with 90% stenosis midsegment, 80% stenosis distal LCX:100% block midsegment, RCA:100% block proximal, Gr. III coll fr. LAD-RCA SVG-RCA:100% block proximal, SVG-LCX:patent, No graft to LAD

48 Introduction of balloon for predilatation is difficult because of extensive proximal calcification & tortuosity, even with buddy wire technique Drug-eluting Taxus stent could cross the bend, but Tsunami stent could be delivered easily to fix the distal stenosis. Second wire was pulled out before stent deployment.

49 Second Tsunami stent deployed to treat stenosis in the midsegment Placement of Taxus stent in the LM

50 Final result

51 Case 2: LM bifurcation stenosis, & diffuse LAD stenosis from proximal to distal segment: T-stenting & LAD reconstruction D, male,55 yrs, unstable angina

52 Case 2 : LM bifurcation stenosis, & diffuse LAD stenosis from proximal to distal segment D, male,55 yrs, unstable angina Bad dissection occurred after predilatation with 2.5/30 mm FX-minirail & was fixed with 2.75/28 mm Cypher stent Angiogram after stenting

53 Case 2: LM bifurcation stenosis, & diffuse LAD stenosis from proximal to distal segment After predilatation, another 2.5/23 mm Cypher stent was implanted to bail-out the resulting dissection Angiogram after stenting

54 Case 2: LM bifurcation stenosis, & diffuse LAD stenosis from proximal to distal segment Tsunami stent was introduced to bail-out distal dissection, Note the nice trackability of the stent across the 2 more proximally overlapped cypher stents

55 Case 2: LM bifurcation stenosis, & diffuse LAD stenosis from proximal to distal segment Nice result after stenting

56 LM-LAD stenting with Cypher 3.0/33 mm Pinching of LCX ostium After kissing balloon dilatation, T-stenting with Cypher 3.0/23 mm After final kissing balloon post-dilatation

57 Case 2: LM bifurcation stenosis, & diffuse LAD stenosis from proximal to distal segment: T-stenting & LAD reconstruction