紫杉醇釋放PTCA球囊導管治療冠狀動脈疾病ppt課件

1、紫杉醇釋放PTCA球囊導管治療冠狀動脈疾病中國醫(yī)科大學附屬一院中國醫(yī)科大學附屬一院 賈大林賈大林內(nèi)容提要2 根本原理 紫杉醇藥物洗脫球囊研討進展內(nèi)容提要3 根本原理 紫杉醇藥物洗脫球囊研討進展4無支架部分給藥的理念 運用經(jīng)皮冠狀動脈腔內(nèi)成形術(shù)PTCA球囊替代藥物洗脫支架DES進展部分給藥 球囊外表的紫杉醇載量是3 g/mm 與藥物洗脫支架DES不同，不需求繼續(xù)釋放藥物 - 擴張30秒就足夠了 基于Paccocath 技術(shù)= SeQuent Please 理念的藥物洗脫球囊，曾經(jīng)證明有出色的臨床前結(jié)論和很好的臨床研討結(jié)果5SeQuent Please基質(zhì)涂層 Paccocath技術(shù) 只需紫杉醇在

2、球囊外表具有生物可利用性(Bioavailability)時才能夠運用短效單劑量藥物。 假設(shè)紫杉醇直接在球囊外表運用，那么就需求一種可以使紫杉醇穩(wěn)定釋放且被迅速吸收進入血管壁的基質(zhì)。 假設(shè)紫杉醇作為一種穩(wěn)定的化合物進展運用，那么所需求的生物利用度就不能構(gòu)成。 穩(wěn)定的化合物 = 純紫杉醇涂層: The SeQuent Please 基質(zhì)涂層 Paccocath 技術(shù) 是紫杉醇和碘普胺的一種分散相。 碘普胺作為一種隔離物使涂層變得疏松多孔，同時也使紫杉醇變?yōu)樯锟衫玫摹?碘普胺的親水特性和紫杉醇的親脂性質(zhì)使藥物可以從球囊外表釋放并進入血管壁。 基質(zhì)涂層 = 紫杉醇和碘普胺:6SeQuent Pl

3、ease 藥物均勻進入血管壁部分給藥的平安性和有效性部分給藥的平安性和有效性SeQuent Please的載藥量是的載藥量是 3 g/mm球囊外表。球囊外表。 只需只需30秒短時間秒短時間的接觸曾經(jīng)足以抑制細胞增殖。的接觸曾經(jīng)足以抑制細胞增殖。約總劑量約總劑量16%的紫杉醇進入血管壁。的紫杉醇進入血管壁。Hwang CW et al., Circulation ,104:600-605, 2019Scheller B, Speck U et al., Circulation;110:810-814, 2019Scheller B, Speck U, Bhm M, Heart;93:539-54

4、1, 2019SeQuent Please 基質(zhì)涂層使藥物均勻分布DES支架的藥物在血管壁呈非均一分布。大約85%的血管壁沒有被支架覆蓋，這導致了藥物在組織中的濃度偏低。.SeQuent Please 迅速釋放 不需求聚合物生物可吸收基質(zhì)涂層短期釋放 300 - 600 g的 劑量球囊接觸部位均一藥物釋放均勻完全覆蓋病變非支架植入單純運用藥物球囊，術(shù)后雙抗治療時間為3個月藥物洗脫支架藥物洗脫支架緩慢釋放緩慢釋放 聚合物作為載體聚合物作為載體涂層可以引起炎癥反響涂層可以引起炎癥反響繼續(xù)給藥延遲愈合繼續(xù)給藥延遲愈合 100 - 200 g 的劑量的劑量藥物僅從支架處分散藥物僅從支架處分散 非均勻覆

5、蓋病變非均勻覆蓋病變植入支架植入支架支架植入術(shù)后服用雙抗藥物至少支架植入術(shù)后服用雙抗藥物至少1年年部分給藥：SeQuent Please對比藥物洗脫支架內(nèi)容提要8 根本原理 紫杉醇藥物洗脫球囊研討進展StudyStudy aimPatientsFollow UpPublicationISR I / IIDEB vs. POBA / BMS-ISR1086, 24, 72 Months2019 in N Engl J Med, 2019 in Clin Res Cardiol, 2019 in JACC CIPEPCAD ISQP / De novo - Small Vessel 1186, 1

6、2, 36 Months2019 in Clin Res Cardiol 2019;99:165e74.PEPCAD IISQP vs. DES / BMS-ISR1316, 12, 36 Months2009 in Circulation 2009;119;2986-2994PEPCAD IVSQP + BMS vs. DES / De novo Diabetics849Months2019 in EuroIntervention 2019; 7: K83 K92 PEPCAD VSQP + BMS / Bifurcations289Months2019 in EuroInterventio

7、n 2019; 7: K61 K65PEPCAD CTOSQP + BMS vs. DES / CTO486MonthsTCT 2019DEBAMISQP + BMS / AMI-STEMI309, 12MonthsEuroPCR 2019PERfECTSQP + EPC vs. EPC / De-novo1206Months2019 in Heart (2019). doi:10.1136/hrt.2019.226563HabaraSQP vs. POBA / DES-ISR (Sirolimus)506Months2019 in JACC: VOL. 4, NO.2, 2019DEB DE

8、 NOVO ISRSQP / De novo + ISR1006, 12 Months2019 in JPMA 61:157; 2019PEPCAD DESSQP vs. POBA / DES-ISR1106Months2019 in JACCINDICORSQP + BMS vs. CFB + SQP979MonthsAsiaPCR 2019SQP-RegistrySQP all comer20959MonthsTCT 2019/ACC 2019OCTOPUSBMS+SQP vs. Xience V956 MonthsACC 2019SeQuent Please 已完成研討一覽表已完成研討一

9、覽表( 3,200 受試者受試者)910PI: Bruno SchellerPACCOCATH ISR I and II在支架內(nèi)再狹窄中運用紫杉醇涂層球囊的在支架內(nèi)再狹窄中運用紫杉醇涂層球囊的一個為期一個為期2年的前瞻性、隨機實驗的結(jié)果年的前瞻性、隨機實驗的結(jié)果Klinik fr Innere Medizin III, Universittsklinikum des Saarlandes, Homburg/ Saar, GermanyScheller et al. N Engl J Med; 35520: 2113-24, 2019 Scheller et al. Clin Res Cardi

10、ol; 9710:773-81, 2019研討組別：紫杉醇涂層球囊組與普通球囊組3 g paclitaxel / mm balloon surface and iopromide (Ultravist)主要終點：6個月節(jié)段內(nèi)管腔喪失次要終點：二元再狹窄率，MACE事件藥物伴隨治療：ASA4周氯吡格雷11TCT, Washington DC, 24 Oct 07Paccocath ISR I/II 6年隨訪結(jié)果年隨訪結(jié)果POBA Drug Eluting Balloon n 54 54 Follow-up 5.2 1.5 yrs 5.6 0.9 yrs Death 8 (14.8 %) 5 (9

11、.3 %) MI 8 (14.8 %) 5 (9.3 %) TLR 21 (38.9 %) 5 (9.3 %) Stent Thrombosis 00Stroke 5 (9.3 %)5 (9.3 %)MACE 32 (59.3 %) 15 (27.8 %) 12Scheller at EuroPCR 2019Paccocath ISR I/II 6年無事件生存率年無事件生存率1314PEPCAD II 研討冠脈疾病中運用紫杉醇涂層冠脈疾病中運用紫杉醇涂層PTCA球囊導管球囊導管 治療支架內(nèi)再狹窄治療支架內(nèi)再狹窄一項對比紫杉醇涂層一項對比紫杉醇涂層 Taxus 支架的預(yù)實驗支架的預(yù)實驗 PI:

12、Martin UnverdorbenUnverdorben et al. Circulation, 119: 2986-2994, 2021PEPCAD II : SQP vs Taxus in BMS ISR 研討目的：評價紫杉醇藥物洗脫球囊對比紫杉醇洗脫支架Taxus stent在治療支架內(nèi)再狹窄的平安性和有效性。研討設(shè)計: 前瞻性，多中心，平行對照研討。15PEPCAD II : 12 個月結(jié)果16No. at riskDrug-coated balloon70706765646362Drug-eluting stent60585653474746BNo. at riskDrug-coa

13、ted balloon70706765646362Drug-eluting stent60585653474746BAesculap Division17PEPCAD II : 3年結(jié)果年結(jié)果 18 “The Paclitaxel-Eluting PTCA-Balloon Catheter to Treat Small Vessel Coronary Artery Disease A Pilot Study“紫杉醇洗脫球囊治療冠狀動脈小血管PI: Martin UnverdorbenPEPCAD I 研討研討Martin Unverdorben et al. Clin Res Cardiol

14、(2019) 99:165-17419PEPCAD I 入選分組情況20PEPCAD IDEB ITTN=120DEB OnlyN=82Taxus*BMS*N=32Follow-up mo6.72.16.71.999Late loss mm0.30.550.180.380.49 0.610.90 0.63Restenosis (segment)15.5%5.5%31.2%49.4%TLR12%4.9%10.4%21.5%Myocardial infarction0.8%1.2%5.7%2.2%Cardiac death0%0%1.9%1.1%Total MACE13.7%6.1%18.9%26

15、.9%PEPCAD I- 6個月隨訪結(jié)果21PEPCAD IDEB ITTDEB Onlyn11482Stent thrombosis1.7%0%TLR11.9%4.9%Death2.9%0%MI1.7%1.3%MACE15.3%6.1%PEPCAD I -1年MACE結(jié)果22PEPCAD I 中的地理性缺失DEB 2.5 17 mmBMS 2.5 25 mm6 month control angiographyDEBBMSRestenosis (N=13)No restenosis (N=16)pGeographic mismatch10 / 13 (77 %)3 / 16 (19 %)0.

16、029Total stent length19.4 8.4 mm14.4 10.2 mm0.035Balloon length stent length-2.31 10.72 mm2.75 7.71 mm0.096PEPCAD IV : 糖尿病患者23Paclitaxel-eluting PTCA-balloon 結(jié)合運用結(jié)合運用(SeQuent Please) cobalt-chromium stent (Coroflex Blue) vs. Paclitaxel-eluting stent (Taxus Libert) 研討研討PEPCAD IV : 類DES 結(jié)果PEB (37Px)PE

17、S (31Px)pMLD FU mm2.01 0.672.11 0.710.40Stenosis FU %29.0 21.225.8 23.60.15Late Loss Stent mm0.51 0.610.52 0.660.94Late Loss Segment mm0.37 0.590.34 0.610.60TLR Segment3 ( 8.1%)3 ( 9.6%)1.00TVR (incl TLR)3 ( 8.1%)4 (12.9%)0.69Myocardial Infarction1 ( 2.7%)2 ( 6.5%)0.59PCI other vessel08 (25.8%)0.001

18、All Deaths3 ( 8.1%)00.24Cardiac Death2 ( 5.4%)00.50MACE (TLR, MI, Cardiac Death)6 (16.2%)5 (16.1%)1.0024Detlef G. Mathey, MDMedical Care Center Prof. Mathey, Prof. SchoferHamburg University Cardiovascular Center Germany The PEPCAD V 分叉病變研討 運用紫杉醇洗脫球囊治療分叉病變PEPCAD V研討 %n= 28 pts., pre PCI vs. 9 month:

19、p 0,001p 0,00126mm pre PCI vs. 9 month: p 0,001p = 0,038Late Loss 0,38 mmxLate Lossx 0,21 mm27PEPCAD V研討 30 day follow upMACE0/28 (0%)9 month follow upDeath0/28 (0%)Late Stent Thrombosis(1x definite, 1x probable) 2/28 (7,1%)Restenosis with TLR1/28 (3,6%)Restenosis without TLR2/28 (7,1%)28PEPCAD V研討

20、SeQuent Please World Wide: A Large-Scale Registry Study of a Paclitaxel Coated BalloonSeQuent Please 紫杉醇洗脫球囊全球大規(guī)模登記研討Prof. Dr. Jochen WhrleUniversity of UlmUlm, GermanySeQuent Please World Wide Registry研討目的與方法研討目的與方法 評價紫杉醇洗脫球囊-SeQuent Please 治療一切能夠順應(yīng)征的有效性和平安性 國際多中心真實世界中的登記研討 主要研討終點 clinically driven

21、 TLR 9 months 次要研討終點 MACE 9 and 24 months MACE事件 = cardiac death, MI due to target vessel, ischemia driven TLR 9個月和24個月臨床隨訪SeQuent Please World Wide RegistryPatientsGermany1452South Africa158Spain143France142Pakistan97Malaysia50 Czech Republic38Switzerland152095 patientsSeQuent Please World Wide Reg

22、istry患者入選分布Number of patients2095 Number of lesions2348Male74.1%Diabetes Mellitus36.0%History of smoking41.6%Hyperlipidemia74.5%Hypertension85.7%Dialysis6.3%ACS16.9%基線分布SeQuent Please World Wide RegistryPatientsLesionsSeQuent Please WWR20952348ISR BMS730807ISR DES457492De-novo with DEB only388476ACS

23、355373STEMI9094Diabetes mellitus754802病變分布SeQuent Please World Wide RegistryMean follow-up 9.4 months結(jié)果SeQuent Please World Wide RegistryMACE = cardiac death, MI due to target vessel, ischemia driven TLRp 0.001Mean follow-up 9.1 months結(jié)果p 0.001p = 0.002p = 0.029p = 0.566SeQuent Please World Wide RegistryMACE = cardiac death, MI due to target vessel, ischemia driven TLRp = 0.010Mean follow-up 9.4 months結(jié)果p = 0.096p = 0.211p = 0.04p = 0.04SeQuent Please World Wide RegistryMACE = cardiac death, MI due to target vessel, ischemia driven TLR小結(jié) SeQuent Please World Wide Registry 研討 是藥物