Presentation on theme: "ZEST Trial -Disclosure Information-"— Presentation transcript:
0 on behalf of the ZEST investigators Comparison of the Efficacy and Safety of Zotarolimus-Eluting Stent versus Sirolimus-Eluting Stent and PacliTaxel-Eluting Stent for Coronary Lesions:The ZEST TrialSeung-Jung Park, MD, PhDon behalf of the ZEST investigators
1 ZEST Trial -Disclosure Information- Supported by research grants fromCardioVascular Research Foundation (CVRF), Seoul, KoreaKorea Health 21 R&D Project, Ministry of Health and Welfare, Korea (0412-CR ) &Medtronic VascularInvestigator have nothing to disclose and no industry sposorship
2 BackgroundSeveral clinical trials have documented that sirolimus-eluting stent (SES; Cypher) and paclitaxel-eluting stent (PES; Taxus) significantly reduce angiographic restenosis and repeat revascularization as compared to bare metal stents.However, the safety of the first-generation 2 drug-eluting stents (DES) (sirolimus- and paclitaxel-) has been concerned by numerous reports of increased late stent thrombosis, myocardial infarction, and death, especially in routine clinical practice.
3 BackgroundZotarolimus-eluting stent (ZES; Endeavor) is a second-generation DES comprising 3 components: (1) a low-profile, thin-strut, cobalt-alloy stent; (2) a biocompatible phosphorylcholine polymer; and (3) zotarolimus, an antiproliferative drug.Although second-generation DES, which may be theoretically less prone to thrombosis, is currently available, large randomized trial comparing first vs. second-generation DES in all-comer settings have been limited.
4 ObjectiveTo establish the safety and effectiveness of coronary stenting with zotarolimus-eluting stent (Endeavor, Medtronic) as compared with sirolimus-eluting stent (Cypher, Cordis Johnson & Johnson) and paclitaxel-eluting stent (Taxus, Boston Scientific) in a multicenter, randomized clinical trial for unselected patients in the real world.
5 Study Design All Comer requiring PCI with DES for coronary lesions Intention-to-Treat AnalysesStudy DesignAll Comer requiring PCI with DES for coronary lesionsin 19 Centers of Korea(Total 2,640 patients)Randomize 1:1:1stratified by 1) Sites, 2) Diabetes, 3) Long lesions (≥ 28 mm)ENDEAVOR®(N=880)CYPER®(N=880)TAXUS Liberte™(N=880)Clinical follow-up at 12 monthsAngiographic follow-up at 9 months
6 Major Inclusion Criteria Significant CAD ( 50% stenosis), amenable to stent-assisted PCISilent ischemia, stable angina, and ACS (unstable angina, NSTEMI)
7 Major Exclusion Criteria Severe LV dysfunction (EF < 25%) or Cardiogenic ShockSTEMI requiring primary PCIOrgan damage (Creatinine 3.0 mg/dl or LFT > 3 times)Left Main DiseaseIn-stent restenosis of DESLimited life expectancy < 1 year
8 Primary Study Endpoint The composite clinical outcome of- Death from any cause- Myocardial infarction (MI)- Ischemia-driven target-vesselrevascularization (TVR)at 12 months after the index procedure.
9 Secondary Study Endpoint Death (all-cause or cardiac)MIComposite of death or MITVR (all- and ischemia-driven)TLR (all- and ischemia-driven)Composite of death, MI, ischemia-driven TLRStent thrombosis by ARC definitionLate loss in both in-stent and in-segment at 9 monthsRestenosis in both in-stent and in-segment at 9 monthsProcedural success rate
10 Outcome Definitions Death was classified to cardiac vs. noncardiac MI: a new pathologic Q-wave or CK-MB > 3 times upper limit of the normal.TLR: any revascularization for a stenosis within the stent and adjacent 5-mm border.TVR: any revascularization for a stenosis at target vessel.Ischemia-driven: (1) >50% stenosis with ischemic signs or Sx. or (2) >70% stenosis even without ischemic signs or Sx.Stent thrombosis by the ARC criteria:(1) Definite, probable, or possible.(2) Acute, subacute, late, or very late.Procedural success: final diameter stenosis <30% without in-hospital death, Q-wave MI, or urgent revascularization of the target vessel.
11 Stenting Procedure Mixture of DES is not permitted by the protocol. If the patients have multiple lesions, all the lesions should be covered with the assigned study stent.If the assigned stent still fails to reach the lesion despite proper pre-dilation, another type of stent (either DES or BMS) may be considered.If the non-target vessel is too large (>4.5mm) to be stented with allocated DES, bare-metal stent can be accepted.Complete lesion coverage is recommended
12 Antiplatelet Regimen Pre-Procedure Aspirin (≥ 100mg) Clopidogrel (loading dose) : 300 or 600 mgDuring ProcedureHeparin: IV bolus + boluses to maintain ACT > 250 sGP IIb/IIIa inhibitors: at physician’s discretionAfter DischargeAspirin: mg /day indefinitelyClopidogrel: 75 mg once daily for ≥ at least 12 months
13 Follow-up Clinical Follow-up 1, 4, 9, and 12 months Angiographic Follow-up9 (±2) monthsAll patients were asked to return for an angiographic follow-up.
14 ZEST Trial - Participants “19 Centers in Korea”1.Asan Medical Center, Seoul2.Yonsei University Medical Center, Seoul3.Catholic Medical Center, Seoul4.Seoul National University Hospital, Seoul5.Ajou University Hospital, Suwon6.Chonnam National University Hospital, Gwangju7.Chungnam National University Hospital, Daejeon8.NHIC Ilsan Hospital, Ilsan9.Keimyung University Dongsan Medical Center, Daegu10.Chonbuk National University Hospital, Jeonju11.Asan Medical Center, GangNeung12.Ulsan University Hospital, Ulsan13.Soonchunhyang University Bucheon Hospital, Bucheon14.Hallym University Sacred Heart Hospital, PyeongChon15.Daegu Catholic University Medical Center, Daegu16.Pusan Natioanal University Hospital, Pusan17.Kyungpook National University Hospital, Daegu18.Yonsei University Wonju Christian Hospital, Wonju19.Korea University Hospital, SeoulSeung-Jung ParkYangsoo JangKi Bae SeungHyo-Soo KimSeung-Jae TahkMyung Ho JeongIn-Whan SeongJoo-Young YangSeung-Ho HurJae-Gun ChaeSang-Sig CheongSang-Gon LeeNae-Hee LeeYoung-Jin ChoiTaeg Jong HongKee-Sik KimHun Sik ParkJunghan YoonDo-Sun Lim
15 Clinical Trial Organization Principal Investigators:Seung-Jung Park, MD, PhDAsan Medical CenterJae-Joong Kim, MD, PhDAsan Medical CenterClinical Events Committee:Data Safety Monitoring Board:Moo-Song Lee, MD, PhDUniversity of Ulsan Medical CollegeClinical Research CenterAsan Medical CenterData Coordination/Site Management:Angiographic Core Lab:CVRF in Korea
16 Randomization ; Computer-generating randomization (Web-based)Data collection ; Electric Case Report Form (CRF)DSMB (data safety monitoring board) ; Site Monitoring and AE/SAE reportingCEC (clinical event committee) ; Events adjudicationIndependent data analysis ; Statistical analysis and final results reporting
17 Sample Size Calculation and Statistical Analysis On the basis of early studies of DES, we assumed an incidence of primary endpoint of 6% in the SES, 11% in the ZES, and 17% in the PES group.We intended to give 90% power to the study and chose an α level of (corrected by the Bonferroni method for the 2 planned comparison in the primary analysis: ZES vs. SES and ZES vs. PES).A sample size of 2640 patients (880 patients per group) was calculated.All enrolled patients were included in the analyses of primary and secondary outcomes according to the intention-to-treat principle.A P value of <0.025 was considered statistically significant.
24 Procedure Characteristics 0.4538.9±25.238.3±24.339.7±26.8Length of stents per patients0.921.6±0.9No. of stents per patient14 (2)491 (41)89 (7)16.2±4.23.5±0.628.9±14.31.2±0.4PES(n=1205)0.6415 (2)19 (2)Use of glycoprotein IIb-IIIa inhibitors0.62514 (42)488 (41)Use of IVUS0.24109 (9)84 (7)Direct stenting0.9516.3±4.116.3±4.2Maximal pressure0.033.4±0.7Maximal stent diameter0.1228.9±13.527.9±13.1Length of stents per lesion0.35No. of stents per lesionPvalueSES(n=1218)ZES(n=1190)LesionsMaxiaml diameterPressure 재 확인
27 Death, MI, Ischemia-driven TVR Primary End Point at 12 month ZESSESPES1510530609012015018021024027030033036014.2%P<0.000310.1%P=0.258.3%Cumulative Incidence (%)Risk 수정 요 .SES vs. PES <0.001Overall P <0.001Follow-Up (Days)No. at RiskZESSESPES
28 Death 1.1% 0.8% 0.7% ZES SES PES ZES vs. SES = 0.77 ZES vs. PES = 0.32 53130609012015018021024027030033036042ZES vs. SES = 0.77ZES vs. PES = 0.32SES vs. PES = 0.48Overall P =0.57Cumulative Incidence (%)1.1%0.8%Risk 수정 요 .0.7%Follow-Up (Days)No. at RiskZESSESPES
29 MI 7.0% 6.3% 5.3% ZES SES PES ZES vs. SES = 0.40 ZES vs. PES = 0.12 155306090120150180210240270300330360ZES vs. SES = 0.40ZES vs. PES = 0.12SES vs. PES =0.45Overall P =0.307.0%6.3%Cumulative Incidence (%)5.3%Risk 수정 요 .Follow-Up (Days)No. at RiskZESSESPES
30 Death or MI 7.6% 7.0% 5.8% ZES SES PES ZES vs. SES = 0.32 155306090120150180210240270300330360ZES vs. SES = 0.32ZES vs. PES = 0.11SES vs. PES =0.56Overall P=0.287.6%7.0%5.8%Cumulative Incidence (%)Risk 수정 요 .Follow-Up (Days)No. at RiskZESSESPES
31 Ischemic driven TLR 7.6% 4.9% 1.4% ZES SES PES SES vs. PES <0.001 105306090120150180210240270300330360SES vs. PES <0.001Overall P <0.0017.6%P=0.0054.9%Cumulative Incidence (%)P<0.0011.4%Risk 수정 요 .Follow-Up (Days)No. at RiskZESSESPES
32 Ischemic driven TVR 7.7% 5.2% 1.9% ZES SES PES SES vs. PES <0.001 105306090120150180210240270300330360SES vs. PES <0.001Overall P <0.0017.7%P=0.0055.2%Cumulative Incidence (%)P<0.0011.9%Risk 수정 요 .Follow-Up (Days)No. at RiskZESSESPES
33 : ARC Definite Criteria Stent Thrombosis: ARC Definite Criteria323060901201501802102402703003303601ZESSESPESSES vs. PES = 0.02Overall P =0.06Cumulative Incidence (%)0.7%Risk 수정 요 .P=0.530.5%P=0.0460%Follow-Up (Days)No. at RiskZESSESPES
34 : ARC Definite or Probable Criteria Stent Thrombosis: ARC Definite or Probable Criteria323060901201501802102402703003303601ZESSESPESSES vs. PES = 0.008Overall P = 0.037Cumulative Incidence (%)0.8%P=0.790.7%Risk 수정 요 .P=0.020%Follow-Up (Days)No. at RiskZESSESPES
35 Stent Thrombosis : ARC Any Criteria 1.0% 0.8% 0.1% SES vs. PES = 0.01 323060901201501802102402703003303601ZESSESPESSES vs. PES = 0.01Overall P =0.048Cumulative Incidence (%)1.0%P=0.620.8%Risk 수정 요 .P=0.030.1%Follow-Up (Days)No. at RiskZESSESPES
36 Major Clinical Events at 1 Months 0.3260 (6.8)54 (6.2)45 (5.1)MACE*NASurgical0.234 (0.5)3 (0.3)PercutaneousTVRTLRDeath or MI0.2557 (6.4)51 (5.8)41 (4.6)Non-Q-wave1.00Q-wave0.2744 (5.0)MINoncardiac0.551 (0.1)CardiacDeathPPES(n=884)SES(n=878)ZES(n=883)N (%)*MACE: composite of death, MI, or ischemia-driven TVR
37 Major Clinical Events at 12 Months ZES(n=883)SES(n=878)PES(n=884)PDeath6 (0.7)7 (0.8)10 (1.1)0.57Cardiac5 (0.6)3 (0.3)5 (0.6)0.74Noncardiac1 (0.1)4 (0.5)5 (0.6)0.27MI47 (5.3)55 (6.3)62 (7.0)0.30Q-wave5 (0.6)3 (0.3)5 (0.6)0.74Non-Q-wave42 (4.8)52 (5.9)57 (6.4)0.26Death or MI51 (5.8)61 (6.9)67 (7.6)0.28TLR43 (4.9)12 (1.4)66 (7.5)<0.001Percutaneous43 (4.9)11 (1.3)65 (7.4)<0.001Surgical1 (0.1)1 (0.1)0.61360일 까지 countTVR46 (5.2)16 (1.8)67 (7.6)<0.001Percutaneous46 (5.2)15 (1.7)66 (7.5)<0.001Surgical1 (0.1)1 (0.1)0.61Primary end point*90 (10.2)73 (8.3)125 (14.1)<0.001*Primary end point: composite of death, MI, or ischemia-driven TVRN (%)
38 Stent Thrombosis at 12 Months Timing of STType of ST0.782 (0.2)1 (0.1)Late0.144 (0.5)Subacute1.00Acute0.047 (0.8)6 (0.7)Definite or Probable0.0489 (1.0)Any CriteriaPossible0.37Probable0.06DefinitePPES(n=884)SES(n=878)ZES(n=883)
39 Results of Quantitative Coronary Analysis are being in the finalizing process and will be reported in the final study outcome.
40 ConclusionAs compared with first-generation DES (SES and PES), the use of ZES results in similar major adverse cardiac events with reference to SES, but in fewer major adverse cardiac events with reference to PES.
41 ConclusionThere was a trend toward lower rates of death or MI in the ZES group as compared with the SES and PES group.The rates of Ischemia-driven TLR and TVR in the ZES group was significantly lower than the PES group, but higher than in the SES group.The rate of stent thrombosis in the ZES group was similar with the PES group, but higher than in the SES group.