医学交流课件：新一代DES的抗血小板治疗

1、 disclosure I have nothing to disclosure regarding this lecture 1st degeneration DES has demonstrated its superior efficacy But safety is always a dark cloud 0.8 1.3 0.0 1.31.3 1.4 2.6 1.2 4.1 4.9 0 2 4 6 8 Late stentThrombosis-Cardiac deathNon-fatal MIDeath or MI Events between 6-18 months (%) BMSD

2、ES Rationales for prolonged antiplatelet therapy post DES implantation BMSDES Late stent thrombosis BMS DES Eos Giant cells -20 -15 -10 -5 0 5 10 15 20 25 Prox. Ref.Prox.StentDistalDistal Ref. Rationales for prolonged antiplatelet therapy post DES implantation Cypher Stent Launch 2003 AHA/ACC Guidel

3、ines 2001 (9-12 months post PCI) (TAXUS stent 6 months post PCI) (Cypher stent 3 months post PCI) AHA/ACC/SCAI Updated Guidelines 2005 ESC PCI Updated Guidelines 2005 (6-12 months post PCI) Optimal Duration of Anti-platelet Therapy Post DES Still Unclear BMS EraDES Era CURE (PCI-CURE) 20011 1 year T

4、AXUS Express2TM Stent Launch 2004 Latest FDA, ACC/AHA/SCAI Recommendations 2006 (1 year post PCI in pts at low risk of bleeding Clinical scenarios need early cessation of anti-platelet therapy InterruptionInterruptionDiscontinuationDiscontinuation SurgerySurgery Seeing other Seeing other doctorsdoct

5、ors CostCost BleedingBleeding PatientPatient unwillingunwilling Younger Younger patient for patient for better QOLbetter QOL NonNon- - respondentsrespondents Dentist Dentist procedureprocedure InterruptionInterruptionDiscontinuationDiscontinuation SurgerySurgery Seeing other Seeing other doctorsdoct

6、ors CostCost BleedingBleeding PatientPatient unwillingunwilling Younger Younger patient for patient for better QOLbetter QOL NonNon- - respondentsrespondents Dentist Dentist procedureprocedure Whats new in new generation DES ? Stent platform Everolimus-Eluting Stents XIENCE V / PROMUS (CoCr-EES) PRO

7、MUS Element (PtCr-EES) 2.6% Molybdenum Durable Fluorinated Copolymer Endeavor DES System PC Technology Drug: Zotarolimus Stent Delivery SystemDriver Cobalt Alloy Stent DES strut and polymer Strut Thickness: 81 m mm Polymer Thickness: 7.8 m mm Total: 96.6 u um Strut Thickness: 91 m mm Polymer Thickne

8、ss: 5.3 m mm Total: 101.6 u um Strut Thickness: 132 m mm Polymer Thickness: 16 m mm Total: 164 u um Strut Thickness: 140 m mm Polymer Thickness: 12.6 m mm Total: 165.2 u um Drug Elution Source: Medtronic Vascular Data Presentation, TCTMD; TAXUS IV SR Presentation, TCTMD; Cypher Presentation, TCTMD;

9、Data on file at Abbott Vascular. Endeavor DESCypher DESXience V DES Taxus DES Resolute DES % Drug Eluted 0 20 40 60 80 100 Time (day) 0306090205080104070110100120150140130170160180 Better endothelium healing in 2nd DES Clinical Data Xience V SPIRIT III and IV XIENCE USA Combined Analysis Endeavor DA

10、TE registry RESET trial SPIRIT III Protocol Stent Thrombosis Subsequent to Thienopyridine Discontinuation P=0.55 p=0.11 p=1.00 N=1/254N=1/123N=2/73N=1/35N=3/144N=1/291 Thienopyridine not discontinued Thienopyridine discontinued before 6 months Thienopyridine discontinued between 6 months and 3 years

11、 Stone G, et al. ACC 2010 Tr SPIRIT III - ARC Definite/Probable Stent Thrombosis Subsequent to Thienopyridine Discontinuation p = 1.00 p = 0.59 p = 0.60 TAXUS XIENCE V N=2/255N=1/123N=2/73N=2/35N=2/143N=2/292 Subsequent Stent thrombosis (%) Thienopyridine not discontinued Thienopyridine discontinued

12、 before 6 months Thienopyridine discontinued between 6 months and 3 years Stone G, et al. ACC 2010 Spirit III: Conclusions Discontinuation of thienopyridine before 6 months appeared to be associated with an increased risk of stent thrombosis with both XIENCE V and TAXUS stents. However, the rate of

13、stent thrombosis in XIENCE V pts in whom thienopyridine was discontinued after 6 months was not increased compared to those who remained on thienopyridine for the entire 3 year study duration. Everolimus-eluting XIENCE V (n=2,458) Paclitaxel-eluting TAXUS (1,229) 3687 pts enrolled at 66 U.S. sites R

14、VD 2.5 mm - 3.75 mm; Lesion length 28 mm Max. 3 lesions with a maximum of 2 per epicardial vessel Randomized 2:1 XIENCE V:TAXUS Express2 Stratified by diabetes and presence of complex lesions Pre-dilatation mandatory Clinical f/u only: 1, 6, 9 months and yearly for 1-5 years Aspirin 80 mg QD for 5 y

15、ears; clopidogrel 75 mg QD for at least 12 mos (if not at high risk for bleeding) SPIRIT IV Study Algorithm Stone G, et al. AHA 2010 Never discontinued n=1460 (59.5%) Timing of First Discontinuation of Thienopyridine Within 2 Years After XIENCE V Treatment (n=2454) Discontinued before 6 months n=145

16、 (5.9%) Discontinued after 6 months n=849 (34.6%) Stone G, et al. AHA 2010 0.3 2.4 0.3 0 1 2 3 4 ST within 2 years after thienopyridine discontinuation (%) N=820 D/C 6 monthsNever Discont. N=1457N=123 Timing of First Discontinuation of Thienopyridine and Subsequent Stent Thrombosis after XIENCE V Tr

17、eatment Stone G, et al. AHA 2010 0.3 3.0 2.1 0.4 0.2 0 1 2 3 4 ST within 2 years after thienopyridine discontinuation (%) N=33N=94N=268 Timing of First Discontinuation of Thienopyridine and Subsequent Stent Thrombosis after XIENCE V Treatment D/C 6-12 moD/C 12 moNever Discont. Median # days off thie

18、nopyridine (IQR) 56 (17, 178) 59 (9, 374) 366 (49.5, 385.5) 196.5 (57.5, 335) - N=552 N=1457 Stone G, et al. AHA 2010 Multivariable Predictors of ARC Definite or Probable 2-Year Stent Thrombosis: XIENCE V Patients Variable Hazard Ratio 95% CI Hazard Ratio 95% CI P Value First discontinuation of thie

19、nopyridine before 6 months (Yes vs. Never Discontinued) 8.06 1.79, 36.220.007 First discontinuation of thienopyridine after 6 months (Yes vs. Never discontinued) 1.06 0.24, 4.730.94 0.011100 Stone G, et al. AHA 2010 Conclusions SPIRIT IV suggested that in pts receiving EES, stent thrombosis is rare

20、when DAPT is discontinued after 6 mos, but not before 6 mos The higher rates of ST with DAPT discontinuation before 6 months might be confounded by specific reasons for stopping DAPT e.g. trauma, surgery XIENCE V USA: Early and Late Stent Thrombosis Rates in 5,054 Real-World Patients from XIENCE V U

21、SA With and Without Dual Antiplatelet Therapy Interruptions Hermiller et al. PCR 2010 58 (supp B):B23 Time (Days)090180270365730 Off-label541752855231518051204955 On-label784277057663759875277347 Overall132591299012894127781264712303 ST (ARC-Defined Definite/Probable) * Off-label vs. on-label 0.00%

22、0.40% 0.80% 1.20% 1.60% 2.00% 2.40% 2.80% 3.20% 3.60% 4.00% 2-year HR 1.89 1.25,2.84 p = 0.0019* Off-label On-label Overall Time Post Index Procedure (Months) 0 123456 789 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 0.53% 1.00% 0.72% ST (ARC Definite/Probable) Hermiller et al. TCT 2011 - JACC.20

23、11;58 (supp B):B23 Time (Days)090180270365730 Off-label541752855231518051204955 On-label784277057663759875277347 Overall132591299012894127781264712303 ST (ARC-Defined Definite/Probable) * Off-label vs. on-label 0.00% 0.40% 0.80% 1.20% 1.60% 2.00% 2.40% 2.80% 3.20% 3.60% 4.00% 0.39% 0.94% 0.09% 0.15%

24、 1-year HR 2.43 1.54,3.81 p 0.0001* 2-year HR 0.40 0.11,1.45 p = 0.1491* Off-label On-label Overall Time Post Index Procedure (Months) 012345678910 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 0.61% 0.11% ST (ARC Definite/Probable) Hermiller et al. TCT 2011 - JACC.2011;58 (supp B):B23 Relationship B

25、etween DAPT Interruption and Stent Thrombosis First DAPT InterruptionP-Value 30-730 days No Interruption 30-730 days vs No Interruption ST subsequent to DAPT Interruption 2.8 % (11/390) 0.4% (13/3239) 0.6% (43/6867) 0.00010.20 90-730 daysNo Interruption 90-730 days vs No Interruption ST subsequent t

26、o DAPT Interruption 2.7% (14/526) 0.3% (10/3103) 0.6% (43/6867) 0.00010.054 180-730 daysNo Interruption 180-730 days vs No Interruption ST subsequent to DAPT Interruption 2.0% (16/803) 0.3% (8/2826) 0.6% (43/6867) 0.00030.04 Stone G, et al. TCT 2011 JACC.2011;58 (supp B):B23. Summary In this analysi

27、s of 13,259 patients receiving EES in a broad cross-section of patients and lesions, 2-year cumulative stent thrombosis rates were 0.74%. DAPT interruption before 30 days was strongly associates with increased ST. Conversely, ST rates were not increased with DAPT discontinuation after 30 days in pat

28、ients who received EES. Hahn JY, et al. Circ J 2010;74:2314-21. A recent registry study reported that low-risk patients with E-ZES + 3-month DAPT (n=661) showed a favorable long-term clinical outcomes after cessation of clopidogrel 3 months post intervention. A New Strategy for Discontinuation of Du

29、al Antiplatelet Therapy: Real Safety and Efficacy of 3-Month Dual Antiplatelet Therapy Following Zotarolimus-Eluting Stent Implantation: RESET Trial Myeong-Ki Hong, and RESET investigators E-ZES (n=146) E-ZES (n=301) E-ZES (n=341) E-ZES (n=271) R-ZES (n=146) R-ZES (n=300) SES (n=340) EES (n=272) Dia

30、betes mellitus subset (N=292) Acute coronary syndrome subset (N=601) Short-length DES Subset (N=681) Long-length DES Subset (N=543) 2,148 patients enrolled and randomized 31 patients excluded - 16 Withdrawal of consent - 15 Met exclusion criteria Divided into 4 subsets and 1:1 randomization was perf

31、ormed. E-ZES + 3-month DAPT (n=1059)Standard therapy (n=1058) R-ZES = Resolute zotarolimus-eluting stent ; SES = sirolimus-eluting stent; EES = everolimus-eluting stents Inclusion criteria Patients with stable angina, unstable angina, or acute MI Diameter stenosis 50% and reference vessel diameter o

32、f 2.5 to 4.0 mm by visual estimation Elective PCI, eligible for participation Exclusion criteria Prior history of cerebral vascular accidents, peripheral artery diseases, thromboembolic disease or stent thrombosis Left ventricular ejection fraction 2.0 mg/dl) Primary end-points A composite of 1) dea

33、th from cardiovascular cause, 2) myocardial infarction, 3) stent thrombosis *, 4) ischemia- driven target-vessel revascularization or 5) bleeding at 1 year post-procedure. * Stent thrombosis, defined as definite or probable stent thrombosis by ARC definition Bleeding, defined as TIMI-defined major o

34、r minor bleeding Post-procedure clinical follow-up; in-hospital, and after 1, 3, 6 and 12 months either by clinic visit or by telephone interview Kaplan-Meier method No. at Risk E-ZES +3-month DAP T 1059104910371027945 Standard therapy1058104610321024920 Primary endpoint Months after the index proce

35、dure Cumulative incidence (%) 0612 0.000.010.020.030.040.050.060.070.08 0 2 8 6 4 Cumulative event rate (%) 0612Months Death from any cause, myocardial infarction, or stent thrombosis Months after the index procedure Cumulative incidence (%) 0612 0.000.010.020.030.040.050.060.070.08 0 2 8 6 4 Cumula

36、tive event rate (%) 0612 Standard therapy E-ZES + 3-month DAPT 1.3% 0.8% p-value by log-rank test = 0.48 Months No. at Risk E-ZES+ 3-month D APT 1059105110451041966 Standard therapy1058105110421037937 Variables E-ZES+3-month DAPT (n=1,059) Standard therapy (n=1,058) Difference (95% CI) p Death, n (%

37、) From any cause5 (0.5)8 (1.0)-0.5% (-1.4 0.4)0.39 From cardiovascular cause2 (0.2)4 (0.4)-0.2% (-0.6 0.3)0.41 MI, n (%)2 (0.2)4 (0.4)-0.2% (-0.7 0.3)0.41 TVR, n (%)31 (3.9)27 (3.7)0.2% (-2.3 2.6)0.70 Non-TVR, n (%)15 (1.5)11 (1.5)0.0% (-1.3 1.4)0.52 Stent thrombosis, n (%)2 (0.2)3 (0.3)-0.1% (-0.5

38、0.3)0.65 1months20 1-3 months00 3-12 months 03 Bleeding, n (%) Major or minor5 (0.5)10 (1.0)-0.5% (-1.2 0.2)0.20 Major2 (0.2)6 (0.6)-0.4% (-0.9 0.1)0.16 CVA, n (%)6 (0.6)6 (0.7)0.1% (-0.1 1.0)0.96 Subgroup Age 3.0mm (n=1448) Lesion length 20mm (n=1301) 20mm (n=816) Subsets Acute coronary syndrome (n=601) Diabetes mellitus (n=292) Long (n=543) Short (n=681) Overall (n=2117) 3Mo-DAPT 20/582 (4.4%) 20/477 (5.1%) 29/682 (5.8%) 11/377 (3.0%) 11/316 (3.8%) 29/743