Diabetes: Es el Talón de Aquiles de los DES?

Transcription

1 Diabetes: Es el Talón de Aquiles de los DES? Oscar A. Mendiz.MD.FACC.FSCAI Jefe Cardiología Intervencionista Presidente SOLACI Octubre 2012

2 Conflictos de Interés Speacker: O Mendiz MD. Astra Zeneca: Speaker Elli Lily, Speaker Medtronic; proctor CoreValve Patrocinio congresos: Abbott, Angiocor, BSCI, Cook,

3 CAD in Diabetics Patients Diabetics have; Unfavorable anatomy (more complex & long lessions) Difusse disease Small vessels More neointimal hyperplasia.

4 Que tan malo es tener DBT en caso de una ATC? Predice la DBT mortalidad y/o reestenosis?

5 Predictores independientes de mortalidad en el seguimento 7106 pacientes post ATC seguidos por 1.4 ± 0,5 años Edad avanzada Tabaquismo Dislipemia ATC a TCI Angina Inestable Infarto Previo Lesión en puente venoso CK elevada (8x) Diabetes Insuficiencia Renal Stone et al. Circulation 2001;104:

6 Predictores independientes de reestenosis en DES: Registros incluyendo off label

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8 Percent Survival Late Vessel Reocclusion in with DBT & Balloon Angioplasty: Impact on Mortality P< Patients without restenosis (n=162) Patients with non-occlusive restenosis (n=257) Patients with occlusive restenosis (n=94) Years Van Belle et al, Circulation 2001

9 PCI in Diabetics: Balloon vs BM Stent p<0.01 p<0.01 p<0.03 Savage MP et al. Clin Cardiol 2002 May;25(5):213-7

10 Restenosis % BMS Stent Restenosis: DBT vs. non-dbt p= p= p= p< p< Modified from. Leon M, ACC 2012

11 SES: SIRIUS Trial Subestudio Diabéticos Resultados a 9 meses p < p < p < % 69% 65%

12 TAXUS IV Subestudio Diabéticos Resultados angiográficos a 9 meses p< p< % 81% Hermiller JB et al. JACC 2005;

13 TAXUS IV Subestudio Diabéticos Resultados clínicos a 1 año p= p=0.004 p=0.01 % 65% 53% 49% Hermiller JB et al. JACC 2005;

14 Incidence Rate (%) Incidence Rate (%) HORIZONS-AMI Diabetic Subset 3-Year Ischemic TLR TAXUS Express Stent: Ischemic TLR Bare Metal Express Stent: Ischemic TLR 50.4 % 9.4% 9.6% 9.7% 9.7% 12.7 % 22.4 % 29.5 % Pts= 1, Pts= Patients w/out Diabetes Non-Insulin Treated Diabetes All Patients with Diabetes Insulin Treated Diabetics Patients w/out Diabetes Non-Insulin Treated Diabetes All Patients with Diabetes Insulin Treated Diabetics Bernhard Witzenbichler, MD, ACC See Glossary for prescriptive information. Not for use in the US.

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16 DIABETES Trial N=160 DBT Ptes (insuline or drugs) 1-3 de novo lesions in native vessels Randomized to SES vs. BMS Clincal and angiographic 9 months mm P < % P < Sabaté M et al. Circulation 2005;112:

17 1. No todos los DES son iguales. 2. No todos los Diabéticos son iguales.

18 ISAR-DIABETES N=250 DBT Ptes with Stable CAD Randomized to SES vs. PES Angiographic 6 & 8 months Outcomes mm p=0.002 Sirolimus % Paclitaxel p=0.03 p= mm Dibra A et al. N Eng J Med 2005;353:663-70

19 ISAR-DIABETES Trial Cypher comparado con Taxus mostró una reducción en la reestenosis sin impacto clínico p=0,03 16,5 % 4,8 p=ns 3,2 2,4 p=ns 4 6,9 Kastrati et al. NEJM 2005;353:663-70

20 DES-DIABETES Trial Cypher comparado con Taxus nuevamente mostró reducción de la reestenosis p< ,2 p= ,8 3,8 4 Lee SW et al. JACC 2008;52:727-33

21 Cypher vs Taxus in DBT (non-insuline 9 months Revascularization Death, MI, Revasc Taxus Better Cypher Better Lee SW, TCT 2010

22 Cypher vs Taxus in DBT (insuline 9 months Revascularization Death, MI, Revasc Taxus Better Cypher Better Lee SW, TCT 2010

23 Que aportaron las nuevas generaciones de DES en los ptes diabéticos?.

24 ESSENCE DIABETES trial n=280 ptes randomized 1:1 (Xience V vs Cypher) Primary EP: 8-months angiographic restenosis p=0,029 4,7 p=0,035 6,5 0 0,9 Kim WJ et al. Circulation Aug 23;124(8):886-92

25 SPIRIT IV: Diabetics Xience V vs. Taxus. p=1 p=0,65 4,2 4,7 p=0,80 6,4 6,9 8,4 8,4 Stone GW et al. NEJM.2010

26 SPIRIT V DIABETICS n=324 Diabetics Ptes randomized 2:1; Xience V vs. Taxus. Primary EP: 9-months angio F-Up p=0,25 6,1 p=0,0001 0,39 3,1 0,19 Grube E et al.am Heart J May;163(5): e1. Epub 2012 Apr 11

27 LEADERS Trial Biolimus eluting stent with biodegradable polymer. Biomatrix vs. Cypher. Non-inferiority Randomized trial. MACE (CV death, MI, 9 months p=ns p=ns 13,9 13,6 9,1 9,9 Windecker S et al. Lancet 2008 Sep 27;372(9644):

28 NOBORI JAPAN Trial Biolimus eluting stent with biodegradable polymer. Nobori vs Cypher. Non-inferiority Randomized trial. MACE (CV death, MI, 9 months p=ns 9,8 p=ns 6,8 4 3,5 Kadota K, et al Catheter Cardiovasc Interv Jul 29. doi: /ccd.23280

29 ENDEAVOR IV Trial Zotarolimus Eluting Stent with biocompatble polymer Vs. Taxus. Randomized non inferiority trial> 1-year Follow-Up in diabetics Ptes 8,6 10,8 p=ns 8,6 9,4 6,9 5,8 Leon MB et al. JACC 2010 Feb 9;55(6):543-54

30 PLATINUM Subgroup Analyses TLF at 2 Years CoCr (%) PtCr (%) Relative Risk (95% CI) Relative Risk (95% CI) P Interaction All randomized (n=1507) 5.8% 4.6% 0.78 ( ) 0.28 Age < 65.0 yrs (n=779) 7.0% 3.9% 0.55 ( ) Age 65.0 yrs (n=728) 4.4% 5.3% 1.20 ( ) Male (n=1074) 4.8% 4.5% 0.93 ( ) Female (n=433) 8.4% 4.8% 0.57 ( ) Diabetic (n=351) 7.9% 5.9% 0.75 ( ) Nondiabetic (n=1156) 5.1% 4.2% 0.82 ( ) Single vessel Tx (n=1399) 6.0% 4.5% 0.76 ( ) Dual vessel Tx (n=108) 4.1% 5.3% 1.29 ( ) BMI < 30 kg/m 2 (n=842) 4.8% 3.8% 0.79 ( ) BMI 30 kg/m 2 (n=663) 7.0% 5.7% 0.81 ( ) RVD 2.62 mm (n=778) 6.3% 5.6% 0.90 ( ) RVD > 2.62 mm (n=728) 5.3% 3.6% 0.67 ( ) Lesion 13.0 mm (n=870) 5.3% 4.2% 0.79 ( ) Lesion > 13.0 mm (n=636) 6.6% 5.0% 0.76 ( ) Binary Rates Stone G. ACC 12. tctmd.com PtCr better CoCr better

31 Events (%) RESOLUTE Pooled Diabetic Analysis FDA Indication Prespecified diabetes analysis designed with FDA for diabetes indication Performance goal prespecified based on meta-analysis: DIABETES, RAVEL DM, SIRIUS DM, TAXUS IV, SCORPIUS, ENDEAVOR Pooled DM.Standard risk patient population from Pooled RESOLUTE matched to performance goal patient population TVF at 12 Months (powered endpoint) 14.5 P = Performance Goal Resolute DES TVF: target vessel failure (cardiac death, TV-MI, and clinically driven TVR) RESOLUTE matched cohort diabetes pooled analysis (N = 878).

32 Cumulative Incidence of Cardiac Death/TLR RESOLUTE Pooled Diabetic Analysis Standard Risk Pts Target Lesion Revascularization to 2 Years 20% 15% Non-Diabetics (N = 1903) Non-IDDM (N = 628) IDDM (N = 250) 10% 5% 5.4% 2.6% 6.5% 4.3% 3.4% 0% 0 2.1% Time After Initial Procedure (months) No. at risk Non-Diabetics Non-IDDM IDDM Error bars indicate a point-wise two-sided 95% confidence interval (±1.96*SE). Standard Error based on the Greenwood Formula.

33 Cómo afectaron los nuevos DES la ATC de Múltiples Vasos?.

34 Stratified for Diabetes Patients with Diabetes in SYNTAX Randomized Cohort, Intent-to-Treat Total Randomized N=1800 All Diabetes n=511 CABG n=221 Medically Treated n=452 TAXUS n=231 Oral Agents n=270 Insulin n=182 CABG n=128 TAXUS n=142 CABG n=93 TAXUS n=89 12-months

35 MACCE % SYNTAX Trial: Diabetics Patients. 3-year Follow-Up p<0,001 p=0,48 p=0,046 36,2 45,9 30,5 29, ,5 Pieter Kappetein MD. TCT 2010

36 SYNTAX Trial; Any 12 months in DBT p=0,001 SYNTAX p=0,72 p=0,43 6,8 8,4 5,8 6,4 p=0,48 2,6 3 5,7 p=0,12 12,5 Banning AP et al. JACC 2010;55:

37 1.Son mejores los resultados con los nuevos DES? 2.Permanecerá la DBT como el Talón de Aquiles de la ATC??

38 SES vs. ZES in Ptes with DBT: SORT OUT III substudy Diabetes (n=390) and NonDiabetes (n= 2384) SES (2332, n=198 DBT) vs. ZES (1170, n=168 DBT); % MACE; HR 4.05;95%IC, MI: HR 8.09,95%IC; TVR: HR 4.94;95%IC, Junkers A, TCT 11

39 MACE SORT OUT IV: Diabetes (n=390) and NonDiabetes (n= 2384) Diabetes Nondiabetes SES p=0.11 p=0.71 EES

40 n=2774 Pts Target lesion revasc. SORT OUT IV: Diabetes (n=390) and NonDiabetes (n= 2384) TVR Diabetes Nondiabetes SES p=0.05 p=0.82 EES No difference in safety or Efficacy between EES or SES in DBT or non-dbt Ptes Jensen LO, Am J Cardiol 2012; sep 4. Pun ahead of print

41 Conclusiones La revascularización es la mejor estrategia en la DBT La revasc tiene peores resultados en la DBT. Los DES disminuyeron los eventos en los Ptes DBT cpmparado con BMS. Todo Dibético debe recibir DES

42 Conclusiones La Diabetes a pesar de la mejoría en los resultados sigue siendo el Talón de Aquiles de la ATC.

43 Gracias por su Atención

44 Outcomes with various DES or BMS in Ptes with DBT: analysis of Ptes years of follow-up from randomised trials Metaanalysis for RCT until April 2012, of four durable polymer DES (SES, PES, EES, and ZES) compared with each other or with BMS for the treatment of de novo coronary lesions in DBT Ptes. PRIMARY OUTCOMES: Efficacy (TVR) and safety (death, MI &, stent thrombosis). From 42 trials with patient years of follow-up, when compared with bare metal stents 1) all of the currently used drug eluting stents were associated with a significant reduction in target vessel revascularisation (37% to 69%), though the efficacy varied with the type of stent (everolimus eluting stents sirolimus eluting stents>paclitaxel eluting stents zotarolimus eluting stent>bare metal stents). There was about an 87% probability that everolimus eluting stents were the most efficacious compared with all others, though there were limited usable data for the zotarolimus eluting Resolute stent in patients with diabetes. Moreover, there was no increased risk of any safety outcome (including very late stent thrombosis) with any drug eluting stents compared with bare metal stents. There was about a 62% probability that the everolimus eluting stent was the safest stent for the outcome of "any" stent thrombosis. Bangalore S, et al. BMJ Aug 10;345:e5170. doi: /bmj.e5170

45 Incidence Rate (%) Incidence Rate (%) TAXUS Post-Approval Registries: Revascularization According to Diabetic Status OLYMPIA Registry 12-month TVR Results TAXUS Liberté Stent ARRIVE I and II Registries 12-month TLR Results TAXUS Express Stent n=7,307 n=1,559 n=746 n=14,456 n=5,692 NOT REPORTED ARRIVE I & II:. OLYMPIA presented by Wagar H. Ahmed, MD, TCT For informational purposes only, not meant as a comparative tool.