大連垠藝冠脈支架

1、新一代載藥技術，更安全的選擇新一代載藥技術，更安全的選擇New Generation Technology，Your Safer Choice垠藝垠藝TMTM紫杉醇微孔載藥冠狀動脈支架系統(tǒng)紫杉醇微孔載藥冠狀動脈支架系統(tǒng)藥物涂層支架的發(fā)展趨勢藥物涂層支架的發(fā)展趨勢聚合物涂層聚合物涂層支架支架可降解涂層可降解涂層支架支架無涂層藥物無涂層藥物支架支架可降解藥可降解藥物支架物支架第一代第一代DESDESCypherTaxusEndeavorFirebirdPartner第二代第二代DESDES垠藝垠藝TMTM第三代第三代DESDES？改良的第一代改良的第一代DESDESExcel愛克賽爾第一代藥物涂層

2、支架的作用第一代藥物涂層支架的作用金屬支架金屬支架多聚體涂層多聚體涂層藥物藥物抑制平滑肌細胞增生抑制平滑肌細胞增生促進內皮細胞生長促進內皮細胞生長抑制炎性反應抑制炎性反應藥物載體、控制釋放藥物載體、控制釋放機械性壓迫斑塊機械性壓迫斑塊機械性支撐血管機械性支撐血管第一代藥物涂層支架的長期狀況第一代藥物涂層支架的長期狀況金屬支架金屬支架多聚體涂層多聚體涂層藥物藥物100%100%代謝，無殘留代謝，無殘留無作用無作用永久存在永久存在機械性支撐機械性支撐永久存在永久存在FDA NewsCordis Corporation Issues a Health Care Professional Letter

3、 Regarding the CYPHER StentCordis Corporation (Cordis) has issued the attached letter to health care professionals to inform them of the rare but potential risk of thrombosis associated with the use of its product the CYPHER Sirolimus-Eluting Coronary Stent (CYPHER stent). This letter also provides

4、clarification on the safe use of the product in accordance with the scientific evidence that led to product approval.The CYPHER stent was approved in April 2003 for patients undergoing angioplasty procedures to open clogged coronary arteries. Since the products introduction it is estimated that over

5、 50,000 patients have received a CYPHER stent. To date, FDA has received 47 Medical Device Reports (MDRs) of stent thrombosis occurring at the time of implantation or within a few days of implantation. The Food and Drug Administration (FDA) is carefully reviewing the reports of adverse events and is

6、 working closely with the company to determine the exact causes and reduce the incidence of thrombosis. From the reports received so far, it is unclear what effect the CYPHER stent has on thrombosis risk and what factors may contribute to the risk. As part of the approval for this product, FDA requi

7、red Cordis to undertake post-approval studies which will help FDA track adverse events more accurately, as well as help determine whether the thrombosis rate in current clinical experience differs from the rate seen in pre-approval studies. Until more is known about the situation, FDA fully supports

8、 Cordis recommendations to health care professionals which may help reduce the incidence of adverse events. These include:Selection of the appropriate stent size. The stent size should match the diameter of the vessel as closely as possible. Selection of appropriate patients for implantation. The st

9、ent is indicated for improving coronary luminal diameter in previously untreated vessels and is not indicated for the treatment of restenosis (reclogging of a previously stented vessel). Use of an adequate antiplalelet regimen. Doctors are reminded to give adequate doses of medication that reduce th

10、e risk of clot formation. Use of the proper technique for stent deployment. The stent should be fully deployed and in contact with the vessel wall. Poor stent deployment is a factor that can increase the thrombosis risk. In addition, all health care professionals are reminded and encouraged to repor

11、t their experiences to FDAs Medical Device Reporting (MDR) System through MedWatch (telephone 1-800-FDA-1088 or /MedWatch). Cordis, in cooperation with FDA, will continue to monitor the issue.Polymer-based sirolimus- (Cypher) and paclitaxel-eluting (Taxus) drug eluting stents have become

12、the treatment of choice for patients with symptomatic coronary artery disease undergoing percutaneous coronary intervention (PCI). Although these stents reduce rates of restenosis compared with bare metal stents (BMS), late thrombosis, a life threatening complication, has emerged as a major safety c

13、oncern. Our understanding of the pathophysiology of late DES thrombosis is derived from animal and human pathologic samples taken after implantation of these devices. These data indicate that both DES cause substantial impairment in arterial healing characterized by lack of complete reendothelializa

14、tion and persistence of fibrin when compared with BMS. Arterioscler Thromb Vasc Biol. 2007;27:1500-1510. Journal of The American Heart Association 多聚體載藥（多聚體載藥（Polymer-basedPolymer-based）支架已被廣泛應用于心臟介入治療中，較）支架已被廣泛應用于心臟介入治療中，較裸金屬支架的再狹窄率明顯降低，但晚期血栓裸金屬支架的再狹窄率明顯降低，但晚期血栓 - - 這一威脅生命的嚴重并發(fā)這一威脅生命的嚴重并發(fā)癥的發(fā)生正逐步顯現(xiàn)癥

15、的發(fā)生正逐步顯現(xiàn) 從動物和人體尸檢標本的病理生理學數據可以看出，對照裸金屬支架，從動物和人體尸檢標本的病理生理學數據可以看出，對照裸金屬支架，多聚體載藥（多聚體載藥（ Polymer-basedPolymer-based）支架導致動脈內膜修復的明顯延遲，出現(xiàn)）支架導致動脈內膜修復的明顯延遲，出現(xiàn)明顯的纖維化和不完全的動脈血管內皮化明顯的纖維化和不完全的動脈血管內皮化 第一代藥物支架多聚體涂層存在的問題第一代藥物支架多聚體涂層存在的問題Pictures from TCT presentation 多聚體材料（選材差、粘度高等）導多聚體材料（選材差、粘度高等）導致嚴重的涂層剝脫或粘連致嚴重的涂層剝

16、脫或粘連 生產工藝不佳導致涂層鼓起或有碎屑，生產工藝不佳導致涂層鼓起或有碎屑，加大了遠端血管栓塞風險加大了遠端血管栓塞風險改良的第一代藥物支架改良的第一代藥物支架“可降解涂層可降解涂層” 新穎的概念，一點點疑問：新穎的概念，一點點疑問：? 藥物釋放的同時涂層不斷降解，兩者能否達到動態(tài)平衡藥物釋放的同時涂層不斷降解，兩者能否達到動態(tài)平衡? 載藥層降解過程對血管內皮修復有無影響載藥層降解過程對血管內皮修復有無影響? 載藥層能夠及時地全部降解載藥層能夠及時地全部降解? 載藥層降解后是否影響支架與血管壁的緊密貼合載藥層降解后是否影響支架與血管壁的緊密貼合第二代藥物涂層支架第二代藥物涂層支架垠藝垠藝TM

17、TM藥物涂層支架的組成結構藥物涂層支架的組成結構放棄傳統(tǒng)多聚體載藥方式放棄傳統(tǒng)多聚體載藥方式 采用首創(chuàng)的微孔控釋載藥技術采用首創(chuàng)的微孔控釋載藥技術國產首個無聚合物涂層的藥物支架國產首個無聚合物涂層的藥物支架垠藝垠藝TMTM支架微孔載藥理論依據支架微孔載藥理論依據參考文獻 Zentralbl Chir. 2007 Jun;132(3):236-46. Tissue engineering: in vitro creation of tissue substitutes Cell Mol Biol (Noisy-le-grand). 2006 Dec 31;52(4):8-16. Hydrogen

18、 peroxide activation of endothelial cell-associated MMPs during VCAM-1-dependent leukocyte migration. J Anat. 2006 Oct;209(4):495-502. Cell-matrix biology in vascular tissue engineering. Circ Res. 2005 Nov 25;97(11):1093-107. Endothelial extracellular matrix: biosynthesis, remodeling, and functions

19、during vascular morphogenesis and neovessel stabilization. Curr Opin Genet Dev. 2005 Feb;15(1):102-11. Cellular abnormalities of blood vessels as targets in cancer. Microsc Res Tech. 2003 Jan 1;60(1):107-14. Angiogenesis in wound repair: angiogenic growth factors and the extracellularmatrix. Am J Ph

20、ysiol Regul Integr Comp Physiol. 2003 Jan;284(1):R1-12. Molecular mechanisms involved in the regulation of the endothelial nitric oxide synthase. Mol Immunol. 2002 Dec;39(9):499-508. VCAM-1 signals during lymphocyte migration: role of reactive oxygen species. Int Rev Immunol. 2002 Jan-Feb;21(1):33-4

21、9. The molecular control of angiogenesis. 材料學文獻中明確指出直徑材料學文獻中明確指出直徑5m5m以下的微孔利于內皮細胞的生長以下的微孔利于內皮細胞的生長 國際材料領域文獻支持上述觀點國際材料領域文獻支持上述觀點確切的動物實驗依據確切的動物實驗依據微孔支架植入兔子體內微孔支架植入兔子體內1010天，可見內皮細胞完全包被支架表面天，可見內皮細胞完全包被支架表面科學的微孔控釋技術參數科學的微孔控釋技術參數1010天釋放天釋放 72%72%3030天釋放天釋放 95%95%6060天內釋放天內釋放100%100%藥物涂層支架的組成結構藥物涂層支架的組成結構完

22、美的金屬支架平臺完美的金屬支架平臺支撐段呈主次波交錯，使徑支撐段呈主次波交錯，使徑向支撐力增強的同時具有良向支撐力增強的同時具有良好的柔順性好的柔順性次波幅短，有效避免了支架次波幅短，有效避免了支架輸送過程中翹起現(xiàn)象輸送過程中翹起現(xiàn)象形波峰增強支架徑向支撐形波峰增強支架徑向支撐力力支架兩端波幅相等，便于支支架兩端波幅相等，便于支架的準確定位架的準確定位主次波主次波形波峰形波峰完美的金屬支架平臺完美的金屬支架平臺 主波間以主波間以“S S”型柔順段連型柔順段連接接 柔順段無銳角，增強徑向柔順段無銳角，增強徑向抗壓性，減少軸向回縮抗壓性，減少軸向回縮S S形柔順段形柔順段 優(yōu)化的幾何構型確保支架優(yōu)

23、化的幾何構型確保支架最佳的物理性能最佳的物理性能 支架外表面和血管壁真正支架外表面和血管壁真正緊密的貼合緊密的貼合 較大的側孔保證側支血管較大的側孔保證側支血管通暢通暢 良好的透視性能以精確定良好的透視性能以精確定位位完美的金屬支架平臺完美的金屬支架平臺徑向支撐力和拉伸強度試驗證明：徑向支撐力和拉伸強度試驗證明： 垠藝垠藝TMTM微孔支架力學性能與非微孔支架無差異微孔支架力學性能與非微孔支架無差異優(yōu)秀的力學性能優(yōu)秀的力學性能歐洲權威實驗室檢測結果：歐洲權威實驗室檢測結果： 垠藝垠藝TMTM微孔支架金屬耐疲勞性能合格微孔支架金屬耐疲勞性能合格以國際標準把握產品質量以國際標準把握產品質量優(yōu)異的球囊

24、輸送系統(tǒng)優(yōu)異的球囊輸送系統(tǒng)球囊材料：聚酰胺球囊材料：聚酰胺遠端輸送桿外徑：遠端輸送桿外徑：2.7F2.7F近端輸送桿外徑：近端輸送桿外徑：1.9F1.9F命名壓（命名壓（NPNP）：）：6atm6atm標定爆裂壓（標定爆裂壓（RBPRBP）：）：16atm16atm折疊方式：三折順時針折疊方式：三折順時針球囊順應性表球囊順應性表1bar0.98692atm 球囊命名壓（NP） 球囊標定爆破壓（RBP）藥物涂層支架的組成結構藥物涂層支架的組成結構垠藝垠藝TMTM微孔載藥支架的藥物微孔載藥支架的藥物 1967 1967年美國化學家年美國化學家WallWall和和WaniWani等首先等首先發(fā)現(xiàn)發(fā)現(xiàn)

25、 一種從太平洋紫杉樹皮中提取二萜抗一種從太平洋紫杉樹皮中提取二萜抗腫瘤成分腫瘤成分 19921992年底，獲得美國年底，獲得美國FDAFDA批準上市，現(xiàn)批準上市，現(xiàn)已被廣泛應用于醫(yī)療領域已被廣泛應用于醫(yī)療領域紫杉醇紫杉醇（PacilitaxelPacilitaxel，商品名，商品名TAXOLTAXOL） 作用靶點為微管作用靶點為微管 作用于細胞分裂的作用于細胞分裂的G2G2和和M M期期 促進微管蛋白聚合促進微管蛋白聚合, ,保持微管蛋保持微管蛋白穩(wěn)定白穩(wěn)定, ,抑制平滑肌細胞有絲分裂抑制平滑肌細胞有絲分裂 對對DNADNA、RNARNA及蛋白質合成沒有及蛋白質合成沒有明顯作用，對明顯作用，對

26、DNADNA模板亦無損傷作模板亦無損傷作用用紫杉醇的作用機制紫杉醇的作用機制 垠藝垠藝TMTM支架載藥量：支架載藥量：1.0g/mm1.0g/mm2 2 理論最大血藥濃度：理論最大血藥濃度：0.025g/ml0.025g/ml 遠遠小于紫杉醇安全血藥濃度遠遠小于紫杉醇安全血藥濃度支架藥物的安全保證支架藥物的安全保證支架藥物的比較支架藥物的比較 雷帕霉素和紫杉醇均能有效地抑制平滑肌細胞的增生雷帕霉素和紫杉醇均能有效地抑制平滑肌細胞的增生 全球大量的臨床使用及試驗均已證明兩種藥物的安全性全球大量的臨床使用及試驗均已證明兩種藥物的安全性 截至目前，沒有任何試驗、理論及文獻能夠證明兩者間的優(yōu)劣截至目前

27、，沒有任何試驗、理論及文獻能夠證明兩者間的優(yōu)劣 截至目前，同樣沒有證據證明雷帕霉素衍生物與紫杉醇的優(yōu)劣截至目前，同樣沒有證據證明雷帕霉素衍生物與紫杉醇的優(yōu)劣 雷帕霉素療效優(yōu)于紫杉醇的觀點是不正確的雷帕霉素療效優(yōu)于紫杉醇的觀點是不正確的 雷帕霉素衍生物療效優(yōu)于紫杉醇的觀點更沒有依據雷帕霉素衍生物療效優(yōu)于紫杉醇的觀點更沒有依據垠藝垠藝TMTM紫杉醇微孔載藥支架紫杉醇微孔載藥支架臨床驗證結果臨床驗證結果垠藝垠藝TMTM紫杉醇微孔載藥支架臨床驗證紫杉醇微孔載藥支架臨床驗證大連醫(yī)科大學第一附屬醫(yī)院和首都醫(yī)科大學附屬同仁醫(yī)院大連醫(yī)科大學第一附屬醫(yī)院和首都醫(yī)科大學附屬同仁醫(yī)院心內科共同參與心內科共同參與垠藝

28、垠藝TMTM紫杉醇微孔載藥支架臨床驗證紫杉醇微孔載藥支架臨床驗證垠藝垠藝TMTM紫杉醇微孔載藥冠脈支架臨床驗證紫杉醇微孔載藥冠脈支架臨床驗證臨床驗證病例一臨床驗證病例一患者男性患者男性臨床診斷：冠心病，不穩(wěn)定心絞痛臨床診斷：冠心病，不穩(wěn)定心絞痛LCXLCX植入一枚垠藝植入一枚垠藝TM支架（支架（3.5X28mm3.5X28mm）一年后病情穩(wěn)定，造影隨訪無再狹窄一年后病情穩(wěn)定，造影隨訪無再狹窄PRE-PCIPRE-PCIPOST-PCIPOST-PCI1 year FU1 year FU臨床驗證病例二臨床驗證病例二患者女性患者女性臨床診斷：冠心病，不穩(wěn)定心絞痛臨床診斷：冠心病，不穩(wěn)定心絞痛RCA

29、RCA植入一枚垠藝植入一枚垠藝TM支架（支架（3.5X23mm3.5X23mm）一年后病情穩(wěn)定，造影隨訪無再狹窄一年后病情穩(wěn)定，造影隨訪無再狹窄PRE-PCIPRE-PCIPOST-PCIPOST-PCI1 year FU1 year FU臨床驗證病例三臨床驗證病例三患者男性患者男性臨床診斷：冠心病，急性心梗臨床診斷：冠心病，急性心梗LADLAD植入兩枚垠藝植入兩枚垠藝TM支架（支架（3.0X18mm3.0X18mm、3.0X12mm)3.0X12mm)術后一年病情穩(wěn)定，造影隨訪無再狹窄術后一年病情穩(wěn)定，造影隨訪無再狹窄PRE-PCIPRE-PCI1 year FU1 year FU臨床病例驗證四臨床病例驗證四患者女性患者女性臨床診斷：冠心病，不穩(wěn)定心絞痛臨床診斷：冠心病，不穩(wěn)定