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Biomaterials Research (2010) 14(1) : 37-49 Biomaterials Research 7 The Korean Society for Biomaterials lp(drug-eluting Stents) w An Overview of Researches Trend in Drug-Eluting Stents Development ½ Á Á½ yá«* Soon-Joong Kim, Jae-Geun Park, Jung Ho Kim, and Il Keun Kwon* Š xfšh Še t Š Department of Maxillofacial Biomedical Engineering, School of Dentistry, Kyung Hee University (Received February 10, 2010/Acccepted February 16, 2010) Since A. Gruentzig performed successful balloon dilatation of coronary artery stenosis in a patient in 1977, the development of interventional treatment of coronary artery disease was truly remarkable. The percutaneous coronary intervention (PCI) has been a great advance in the treatment of coronary artery disease since implantation of bare metal stents (BMS) decreased acute recoil and arterial shrinkage caused by balloon angioplasty. However, neointimal hyperplasia leading to in-stent restenosis after BMS implantation has been emerged a new obstacle. Recent introduction of drug-eluting stents (DES) contributes a powerful breakthrough to PCI. DES overcame restenosis, the impregnable limitation of PCI. Many large well-controlled randomized trials have shown that DES remarkably reduces restenosis and target vessel revascularization in de novo lesions when compared with BMS. Therefore the application of DES have been expanded to the complex lesions such as left main, multi-vessel, bifurcation, in-stent restenosis, or chronic total occlusion. The safety and effectiveness of DES are still under evaluation with ongoing trials. However, some problems such as very late stent thrombosis remained to be solved. In this review article, we summarize research trend in DES development. Key words: Neointimal hyperplasia, Restenosis, Thrombosis, Drug-eluting stents lœf Œ l,, l Œ, hl fš f t Š, u 10 Œ Œf Œ Œ Œ f f Š f 6 lš f f jd eff f. j Œl, Œh Œf v fš e f g f lœf lf hf. f Œ Œ lœf h e ff 1e rlš f, f d f f df f lœf x Š f hf. u d Œ h Š l v ff, f Š lœ Š x f Š t f f Šf fdš u hš f. hf x f h ˆ Œ g (percutaneous transluminal coronary angioplasty, PTCA) i l Œ e s f ~ f ˆ f f f Œg z f d f Š fd f. 1987 f fd f ƒ f if f Š *sf hf: kwoni@khu.ac.kr f Š h fd ff h ˆ Œg ƒ f f hr l f. Šl ƒ f 6 e Œ fš ƒ gœref 30% h l l h f f f hf Š Š Š jdš hhf f. ƒ, ƒ gœr(in-stent restenosis, ISR)f x f ~ f fdš i d f fl fl, l 11~20% f Œ g (target-lesion revascularization) dš g h h Œhl f h h f. jg f j hhf gœrf Œ f j w f Š Œ f Š l d lf Œ ( ) f h f u if ƒ l hh(antiproliferative) hh(immunosuppressive) f Š hhš f f g l hf v Šf Œ ef h Œ g (pathologic arterial remodeling) Œ (neointimal hyperplasia)f hš gœrf Š Œ f. Šl hf gœr, Œh(late thrombosis) f h Š f f f l h f h ff f. tm, fš Š l ff h f g f x hf h d 37

38 já g Á hœá f l h f Š l Š late catch-up f d ff, m, Œ f f g f h f ll Œhl f f f f, m z f fš l(hypersensitivity) fš h Œ g f fš (coronary artery aneurysm) f Š f f. f u d hf lœ jgh x f h, f i ƒ, ƒf i, v ƒ(drug-eluting stent, DES)f z f eš ŠŒh Œ d ff i g d, hh Š, v ƒf Šd, z f e d g Š Š f Š. y e ƒ f x f f Charles R. Stent f f Š eš ll jœf Š ff f f f f f e. i l f 1) hf f lh jf x Š jg f 1977 e f Andreas Gruentzig fš ihššl Œr h ˆ Œg (percutaneous transluminal coronary balloon angioplasty, PTCA) f hf ŠŠ ŒrlŒ x f d g f. ˆ Œg f g x f ff 2,3) hf f ƒ f f Š fd f gœref f f f hšhf. h jg (percutaneous coronary intervention, PCI)f g (revascularization) x f f f, 1983 Š f Š g fš sff ˆ Œ f Š. f Šr 4) 1986 Puel Sigwart fš ƒ sff, ƒ f, ff vh, d ŠŒ h d f fš x hf Š Š hf Š, 1993 fe f f BElgian NEtherlands STENT (BENESTENT) STent REStenosis Study (STRESS) ƒ f ˆ Œg Š gœre g f jf f f, f ƒ f lœ jx f j vf f Š. 1990 j 5,6) ƒ f h hf jg f Œ, Œf fr jg (primary PCI)f Œh dšh d hf ŠŠ if hf Š fš, d 7) x Š Œ lœ, ij l Œr ƒ f Š. 8) Šl, ƒ f ˆ Œg f x hf hf f v(acute recoil) Œ r(arterial shrinkage)f j l, Œhl(subacute stent thrombosis) ƒ Œ (neointimal hyperplasia) d hhf z. f ˆ f fdš ƒ r(apposition) Š fj ŠŒ h( + } } ) fdš d f hf ƒ Œhlf d j. 9,10) v (Percutneous Coroanry Intervention, PCI) h jg f f d f Š e f(guiding catheter) f f ~ e s f fdš ˆ f, hh f, hhh f, fh f, ƒ f Œr f fy f. ˆ Œg (Balloon Angioplasty) ˆ f fdš Œr f f, g } hšhf jf l Š fš lf 5~10% h Š, Œff f, lœf h, f Œ~Šh ƒl f Š. ˆ Œg f v 11,12) (constriction) Œ (neointimal hyperplasia) f Š 6 e 30~50% gœrf Š, 13) ˆ Œg f hf Š ƒ f f ˆ Œg f j ƒ f g Š f Šj ih f ƒ f d ff Œ lœ Š f. ƒ f (Stent Implantation) Œrf Œ ~ eš dš ƒ Œ,,, d, f hd ff d j Œ ƒ ej Š ff fdš ƒ Š i Š. if ƒ f z Š f v h (local drug delivery) f v ƒ(drug eluting stent, DES) f Œ ƒ DES j ƒ d ff Œ Š eš Š z f f. 14) a. Bare Metal Stent Implantation Œr e f ƒ eh f ˆ f f ˆ f ƒ Œg ~ f, ˆ Œg f hhf Š Š f, ƒf Œg ll f vf lš gœref 20~30% z. 15,16) ƒ f f lf t ƒ ŒhŒ f h f, ˆ f ƒ Œ g f ŠŒ h(ticlopidine, cilostazol ) 1~2 e Biomaterials Research 2010

v ƒ(drug-eluting Stents) f u 39 d Šf Œh fš 1% f jf f. u 17) stainless steel gh f f z ƒ/} Š f ƒ f f, v ƒ(drug eluting stent)f g f bare metal stentf d } Š., ƒ h t f df hš jdš fff v ƒf ~ f d jdš. 18) b. v ƒ f (Drug-Eluting Stent Implantation) ƒ f gœref 20~30% fl,, ff Œ, Œf f ƒ gœref 30~40% f, f fš hf g f } hšhf f. jg g 19) Œrf jdš hf v Œ f. ƒ f z Š f l hh(antiproliferative) hh(immunosuppressive) hhš vš ƒ f v, f l Š f v ƒ, t f d d Š f l f hš f, f Œf ƒ 20,21) h f fl g l d f. 22-27) v ƒ f i f ƒ f r f ff gœref 15% fš, g ef 6% fšf. Š, Œ lœ,, ff Œ, f Œf gœr g ef Š h ~. f d ƒf 90% f f v ƒ rl Š f. Šl, v ƒf hšhf ƒ ŒhŒ f, ŠŒ hf i j, hl,, i hš, l, f f, ff Œ f e ff f. ef 2% f l, f Š f, e~ Š ff e ff f Œf Š jf dš. gœ (Reendothelization)f 28-30) h, f h Š (hypersensitivity) fš Š f vw, v ƒ 31) aspirin clopidogrel Š d f h 6 e f 1 l Š Š, aspirinf dš Š. g Cypher (sirolimus) ƒ TAXUS (paclitaxel) ƒ f d f. j h (Coronary Atherectomy) i f fdš j f h Š g ƒ Š d ˆ Œg f ƒ f ih f hšhf Š f. s, ee h Š Š l e f ff f Šd Š. Directional coronary atherectomy (DCA) h x f hh f fdš j f hhš f f j il f hgš h Š hf i l f f f ghf f. Œr f j f d f d, x,, l e, ij l ŠŠ f. Percutaneous coronary rotational atherectomy (PCRA) f (burr)f f h z j f d ff ff Œ f, Š Œ, f, h, l e, gœr dš f. Coronary laser angioplasty dš f Š e e f Š fh l h z j f Œ z h Š f, hœr f ƒ gœr dš f. lp ƒ Œ f Œhf fš, Œf l Œf Š g Š f, i l Œ e fš Œ f f h Œ ~ d e Œf ƒ f l h f ƒ gr f f f f ƒ e f l f r f i l e j Šf Š. f Š ft f l, Œ,,, g f Œ f f, t f eš fš eœš Œ, f f f f z Š. ƒ l i f eh f f Š f Š f Š. f i Šl t j. f ƒ h ˆ Œ f ˆ e fš f. r l fš e ƒ f ˆ f ex ~ ˆ f ˆ f ƒ f llš f f f f. ƒf glf f f jif f f. f hf ƒ Œ Œrf Š Š f ~ h f Œg Š, Œg ~ f l g ftf r f fdš f ŒgŒ(Self-Expandable) ƒ d f, l ˆ f fdš ˆ ŒgŒ(Balloon Expandable) ƒ f. wx š Œ f f fdš f g, ƒf l, jštf Š z, t l, Š Št f Š Œh f f. Š Œ t ilf lf Œ f f fd Š til l g, tissue patch fd ff, h r gl f e tf f df f. 32) Vol. 14, No. 1

40 já g Á hœá f Œ d ff i l f d g d ff, ƒ f l f Š,, e, ˆ Š f d d e Œ f. Œ f f f d ff, jd d ff i ƒ f f Table 1. Œ d g f d hh g Table 1 f f f d d ff ftf Ž xl Š f f. hf f d g v Š d ƒ Œ d g f hhf Table 2. lp(drug-eluting stent) v ƒf f if bare Œ ƒ f Š, f z Š f vf h Š f, f ŒŠ f. 33) f z v ƒ f lš } l Š f, f ƒ lh rš, (porous) ƒf (pores) f Š, ƒ z Š f f ŒŠŠ f f. z f v h f ƒ id, f f hf r f d Œ (diffusion) fš f v f Š f f h lš ff v h f } fš ih. f Š f f d Œ fš f v f d v h f z f fš h f. g f dš f d v ƒf Cypher Taxus f fš f v. f f ŒŠ Šf Š Š ŒŠ Šf l h f v h ihš f. fd Š f f f Š f Š dv, f z ƒ ƒ f f v f f. v ƒf f ƒ glf i, f s, f z, ff i Š d Œ Š lš ff ƒ } l fdš Š h, fff z, l f f f z Š Š f f l f. d v ƒ lœ ƒ f f l ff 15~30% ƒ gœrf h f jf eš Table 1. Œ d ff i g d l, hl f Œ Œ f Œ h shunt z ƒ td Œ ˆ, x ~ d ~ z h l PVC ~ ( ) g l t l } ƒ Š EVAL PMMA PVA ƒ ƒ z v Œˆ, ƒ z ˆ j f x ~ g lead f i g, f g f gil td Œ ˆ, x ~ g } x ~ Œ / Œ /, Œg Œ Œ /, Œg f, Œg Œ Œ /, Œg Œg Table 2. f d g f d Œ d g f v hf hh h Œ hš (blood compatibility) f d g f d ilhš (tissue compatibility) h Š t h (stability) Œh (thrombus) Œ d g f hh Œ (calcification) (infection) v ƒ f f h f h f Œ~f. v ƒ Š l, Šl f hf f dš gœrf ~ f Š f hf g Š Š f fdš ƒf. ƒ paclitaxelf z Š v ƒ(taxus, Express) hhf sirolimus eluting stent (Cypher) fdš f h hf v ƒ gœrf f z if bare stent tš f v f. 34) Table 3f g i f Š gœr f drug coated stent d f f ~ f. 35) v ƒf hh v ƒ f f f ƒ Š gœr jd g f jf d Š hf, v ƒf (The Era of DES) f } lœf x Š~ Œ z l, g vh r l hh f l fš. 36) a. ƒ Œhl ƒ f lf Œ v f, Š hf Œh Œ f e f l Š. f Š eš, Biomaterials Research 2010

v ƒ(drug-eluting Stents) f u 41 Table 3. Drug coated stent d f Paclitaxel (TaxolTM) Taxol derivative (QP-2) Antineoplastic Actinomycin D Vincristine Hirudin and iloprost Antithrombins Heparin Sirolimus (RapamycinTM) Tranilast Immunosuppressants Dexamethasone Tacrolimus (FK506) Halofuginone Propyl hydroxylase Collagen sythetas inhibitor C-proteinase inhibitor Metalloproteinase inhibitor Angiopeptin V VEGF VEGF, vascular endothelial growth factor. ƒ tr,, ŠŒ hh f r fd, f Œh ef 1990 t 20% u 0.2~1.8% jf Š f j f l Š f. Šl 2003 v ƒ 6j Š Œhl, 2004 1 Š Œhl r, v ƒf h Š f Œ. ƒ Œhlf hf 37,38) Š, jf f Š, Š df f. f tf eš,, e f f j f ff Academic Research Consortium (ARC) 2007 ƒ Œhlf hf h Š, f f j l xf f. f lx ƒ Œhlf f 39) f eff f Œ l (definite, probable, possible), f f Š hf jf early (1 e f ), late (1 f ), very late (1 f ). ~, 1 f (early, late) f ƒ v ƒ f Œhlf 0.5% d rf f. h 1 Š 40,41) very late ƒ Œ hlf, v ƒ 42) (sirolimus-eluting stent, SES; paclitaxel-eluting stent, PES) very late ƒ Œhlf f ƒ(bare metal stent, BMS) Š ff ~ f Š (0.6% vs. 0%, SES vs. BMS, p=0.03; 0.7% vs. 0.2%, PES vs. BMS, p=0.03). 43) ƒ Œhlf f, l f Š f Š d f f l f, Šl Œhl fš f 7~45% l h f. f Š v 44-48) ƒ h d 2006 e gš f v v ƒ f ƒ Š, f l ~ fš hh f, f 49) Š h, s f ff h f, f fš f f v ƒ f ƒ f efš rf f ~. 43,50,51) dy, very late ƒ Œhl f v ƒ l, f Š hf gœr g f fš f f h f Š Š f. Œhlf jf e Š f ƒ dš f d(, f Œ, lf, f, (ostial) )fl l Š, hhš ŠŒ hh Š Š Š. g lš f f f h f ff f. b. ŠŒ hh d f lœ Œf dš f e. ŠŒ hh Š f j f } f d f. Œhl Š d } d g Š j, 2005 gš / gœ l lx 12 e df f hf f f 2007 l lx v ƒ } f u Š 12 e dš Š. f Š g df vœ f l, d l, h f d f h ffz, hhš } d Š h i ŠdŠ Œf Š. c. d- h f ƒ Š v ƒf df, f d- f h. l f, f df ŒŠ f l f f fl, 52,53) f Œ g ƒf v u v ƒf f j Š Š v, t Œ Š d- f f f. lp 1 v ƒ Cypher Taxus f u l f df f e f f ƒ 10 if (Cypher Select, Taxus Liberte, Endeavor, ZoMaxx, Xicence V, BioMatrix, CoStar, Supralimus, Infinnium, Nobori, Janus, Genous ). j u f f f, j f d f fdš ƒ, t Œ jšt(bioabsorbable polymer), t ŠŒ ƒ(biodegradable stent), Œ rœ ƒ(endothelial progenitor cell capture stent)f. j d - Zotarolimus Everolimus Zotarolimus sirolimus r l mtorf f r Š hf l f, sirolimus Š il f f f f. if v Vol. 14, No. 1

42 já g Á hœá f ƒ Š utf Endeavor III f 436 f 8 e rš, f h fš g } rf l (6.3% vs. 3.5%, p=0.34), gœre Cypher Š Šf r (11.7% vs. 4.3%, p=0.04). 54) Everolimus sirolimus e tf. u h h fe f SPIRIT III fš, everolimuseluting stent (Xience V) Taxus gœref f f rf l (4.7% vs. 8.9%, p=0.07), 1 jd g f f jf f (6.0% vs. 10.3%, p=0.02), r v ƒ j g l g Œ Š f f. 55) f l d ƒ u KFDAf ff, Š fš. d ƒ ff v ƒ h Œhlf eff, h tf jšt ƒ ft l. f Š eš u f ƒ jšt j f Œf, t Œ jšt dš, g hf ƒ Š l Š f l f. 56-59) Š Œ h (endothelial progenitor cell)f g, ƒ f r(reendothelialization) Œ xe hf tlš ƒ ŒŠ t hf Š. 60) lp(stent) w f jg f 20,000 f, f ƒ Š 1,000 e f f. f Š, ƒf Œ h ˆŒ Š jf. f z Š ƒf d d g 2 l h Š f hf. ( Š ) fdš ƒ fh ff, l f Š fl. ƒ Š hf g Œff 15~30% e Œ f Œr g f Š, g rf lš ƒ f. 61) g r l eš ƒ a. Drug-coated stent a-1. Heparin r ƒ l gœr Œ heparin r ƒf r Š, ƒ l f hš gœrf efš ~ f rš ff, f gœr Š h flšl Š. Heparin dexamethasone f Œ Œ f l f hš. BENESTENT-II r Palmaz-Schatz ƒ f Œf ƒ Œh Œ fš Š l f f, 6 e vh r BENESTENT-If i ƒ Š Š f h ief vh i gœ re 20% 13% efš Š. h hf Šf d f r ƒ elš h hf Šf d f Š ŠŠ f Š f, f h h gœre rf fl f, r ƒ vœf Š lf fl. u f ŒhŒ h hf f l h Š f f. a-2. Rapamycin (Sirolimus)-coated stent gf f gf d Š hhf rapamycin (sirolimus)f Œ smooth muscle f l f f hš f l f, f Š Œ lš Sousa f 32 f f rapamycin-coated stent Š 8 e vh r Š 3 f 15% f f l f r x Š Š f edge stenosis Œh Œ f, jd g Š Šl Š rapamycinf gœrf hff Š. a-3. Paclitaxel-coated stent Paclitaxelf llxœ (lipophilic)f Š Šl fd f f f hš microtubule hœ h e,, f Œ d. Š fdf ~ Œj 100 h ~ paclitaxelf Œ Œ f f PDGF fš l f hšf hf, f f fdš hf h paclitaxelf gœrf Š fff h. de la Fuente f 32 f Œf f paclitaxelf r ƒ 1 r jd g f i f Œ t f gœrf Š f. g ASPECT trialf ELUTE trialf lš f. a-4. ReoPro-coated stent f l fš ReoPro r ƒ Š l gœr Œ Š rš f. ReoPro r ƒ(i : ReoPro-coated stent) r l f ƒ l Œg f Š Š 4j vh i ilšh f Š. ƒ Œhf Šl f, 4j ilšh Œr f ReoPro r ƒ efš. l, Glycoprotein IIb/IIIa receptor blocker r ƒ i ƒ Š l f hš ƒ gœrf Š fff f. Biomaterials Research 2010

v ƒ(drug-eluting Stents) f u 43 b. Radioactive stent u brachytherapy ƒ gœrf Š f f ff 2000 FDA gamma beta radiationf ƒ gœr Š hf PCIf f ff Š. Iridium-192 gamma radiationf f dš SCRIPPS (Scripps Coronary Radiation to Inhibit Proliferation Post Stenting Trial) i f 54% gœr Š 17%f gœref ƒ l f 66% f. x } lf h f f x~ fdš hf f f f i Š ƒ fdš hf f g i Š f, i f i x~, ee coating ˆ f ƒ, ee solution-filled balloon f ff f f f. f i diffuse formf f Š hf f. WRIST (Washington Radiation for In-Stent restenosis Trial) Ir-192 fdš ƒ gœr Š 6 e vh r Š i Š jd g (major adverse cardiac events) h. WRIST gœr x f ef f edge stenosis (candy wrapper effect) h f d. f x e g f ŠŒ x f ƒ gœr Š ŠdŠ. i gœrf x Š f ff l Š l Š f Œh Œ (late thrombosis), unhealed dissection, late stent malapposition f. c. Drug-eluting stent ƒf gf f gœrf. Šl ƒf u h f l f ƒ gœrf d x ~. g ƒ f f f Œff 20~40% ƒ gœrf f f. ƒ gœr d f f d Šdf f ŒŠ f j f f h v v ƒf. f f ƒ g Œrf h ~ f. v ƒ hˆf i i y(johnson & Johnson medical) Á z (Cordis corporation) f Cypher (sirolimus-eluting coronary stent) f. h v z j u g Œ Š f f Š h hh f v Š l f lh h ~ ~ff ƒ. f Š ~ f j g j f sirolimus paclitaxelf. Sirolimus f Œff ff hš hh. j g f d f (f f hd). Paclitaxelf f i f f x Š fd Š h g h f. d. r f ƒ - t self-expanding stent h Œ (PTCA) ƒ fd l 20 f ff, g PTCAf 60% f f. g f hf d ƒ g h f t f h f h f lh f. t ƒf f ff, f f Š f ~f. 2005 f A.Z. ƒ- d e Œ d g } Š ƒ h Œ h il f f 9:1f e f gx 1jf~10 f Œ fš 60f h l ƒ Š (2005 1e). Šd Šd l f jf f } Š f. ƒ Š f Š Œ s jf eš Š ff, f Œ lœfl, eff Š f Š Š ef ŠŠ, hhš v f, f g iš ƒ d e fœ Œ f rš l ŒgŠ f f f. ƒ Š f d Š t Š f. i h f f f. f hf t Œ~ Š Œ~ Œ Š ff, gl ft ŠŠ, h f f Ni-Ti Š, z f Œ f l hf hf Š f. lp(stent) w Šd g a. g Œ h ƒ i i y(johnson & Johnson medical) sf f f, df lš, ƒ fdš Œ Œ 1995 80% f l Š. jd t f (Bostnon Scientific Corp.), f ƒ(guidant Corp.), i i yf, Wall Street Journal (2004 5e), 2003 f t f Œ Œ d wires, Ballons, Catheters, ƒf g 60 f l Š. Table 4 1997 ƒ ˆ Š g hee f j f. f, i i y, ƒ f f jg Œ f f fy f gœ l f x Š g Vol. 14, No. 1

44 já g Á hœá f Table 4. f ghee hˆ jg 62,845 f g (24.4%) ƒ 13.080 i i y (64.2%) PCTA ˆ x 37,580 f g (38.9%) PCTA e x 4,145 i i y (39.6%) PCTA e j 5,270 f ƒ g (52.8%) hi f ghee 1 2 3 4 i i y (23.2%) ƒ g (21.9%) f ƒ g (14.1%) f f (13.8%) f f (22.8%) f ƒ g (15.1%) z ~ (13.9%) i i y (11.4%) Œfh (10.3%) g (8.9%) [ e : ] ƒ g, g, fh (37.3%) - g, Œfh, (35.6%) f g, f ƒ g (36.3%) f g, i i y (15.5%) f : Medical Equipment Almanac 1998, R&D, Inc Table 5. 2003 ~2011 v ƒf g Œ h [ e :m$] 2003 2005 2007 2009 2011 CAGR(%) g 2,032.33 3,458.55 5,371.67 7,805.82 10,597.95 19.50 f : Global Industry Analysts Inc. Drug-Eluting Stents, 2004 10e Œ Š ex f f f f rlš g jf f. g Šd ƒ gf hf f i i y, f ƒ f f. i i y z ƒ f tf, f ƒ f f ƒ x gh ƒlhf gh f fff Š fš Š jf. ƒ f ƒ 2002 30 (Cook) f Šf f gf Š gf j f. f Š ƒ gf 40 f f gš f, Š ƒ f hœ f l gef d l Š f l. Table 5 Figure 1f v ƒf g Œ h f ~ f. v ƒ 2003 2,032 m$ gf Œ Š f, 2005 3,459 m$ gf Œ, 2011 vf 10,598 m$ gf f f, CAGR( h g ) 19.5% gš f w Š f. b. l v ƒ g Œ h v ƒf 2003 ~2011 l l g Œ h f Table 6 Figure 2 ~. l f }, f, e, d l f v( e :m$)f v Š. g } v ƒ gf f f 2003 1,517 m$ gf Œ Š ff, Š CAGR 17.5% l Š 2011 6,309 m$ f gf Œ Š f h. f f 2005 389 m$ f v ƒ Figure 1. 2003 ~2011 v ƒf g Œ h. gf Œ Š, CAGR 24.68% } f gš f v. 2011 1,565 m$ f gf Œ Š e g } gf f ff } v ƒ gf gš f h Š f. e f 2003 274 m$ f f v ff, CAGR 18.2% gš 2011 1,102 m$ f g f Œ Š f. d l Š CAGR 25.14% } g f gf l Š 2011 1,531 m$ f gf Œ Š f Global Industry Analysts Inc. h Š f. Table 7f l v ƒf g hee Œ ~ f. 2003 75%, e 13%, d l Biomaterials Research 2010

v ƒ(drug-eluting Stents) f u 45 Table 6. 2003 ~2011 v ƒf l g Œ h [ e :m$] 2003 2005 2007 2009 2011 CAGR(%) US 1,517.54 2,306.16 3,440.55 4,882.54 6,399.04 17.52 Japan - 389.43 707.45 1,085.01 1,565.32 24.68 Europe 273.96 382.17 588.73 835.22 1,102.19 18.29 Rest of World 240.83 380.79 634.93 1,003.05 1,531.40 25.14 f : Global Industry Analysts Inc. Drug-Eluting Stents, 2004 10e Table 7. l v ƒ g hee Œ [ e : %] 2003 2005 2011 US 75 67 61 Japan - 11 15 Europe 13 11 10 Rest of World 12 11 14 f : Global Industry Analysts Inc. Drug-Eluting Stents, 2004 10e Figure 2. 2003 ~2011 v ƒf l g Œ h. f 12% g Œ Š f f, f f l g f Œ Šl Š. 2011 61%, f 15%, e 10%, d l f 14% ff f f v ƒ gf Œ Š f h Š f. Figure 3f 2011 l v ƒ g heef ~ f. c. jd t v ƒ g Œ c-1. jd t v ƒ g Œ v ƒ hiš Š jd t i i y, f, f ƒ, ƒ, f. 2004 i i y v ƒ g f 47.3% rlš f, ff, ff f } g f i i y f vf v Š f. f v ƒ gf 32.6% rlš f. c.2 jd tf v ƒ gˆ c-2-1. f (Boston Scientific), gœ rf j } ~ (paclitaxel) ƒ v ƒ dš ~ gœr(restenosis), Taxus } ~ (paclitaxel) v ƒ dš jf f The New England Journal of Medicine. Taxus f f glf Œ ƒf. f, Taxus f ƒ Š Œ f f Š Šd f j j. df g, Œ (Lenox Hill Heart and Figure 3. 2011 v ƒ l g hee. Vascular Institute)f Gregg W. Stone lf 1314 f Œ gœrf f Œf l f Taxus f ƒ Š. l f Š f. 4 f 1f f f f, ef f Š. Œf d ƒ f Š. ef Œ f Taxus Š d 3% ~ f 11.3% Š hš f x ~., Œ gœre 7.9% ~ f ƒf 26.6% Š. f ihf, f ƒ Œhlf fš f ƒ f } rf ~ l. g Taxus ƒ hš f hl, g f h Œ v ƒ f eš lš Š. c-2-2. f ƒ(guidant) Š ƒ FDA f ˆf ˆ h f f f j dš f d i f ƒ hˆf fš. f hˆf fdš f l jd Œ f f f x Š f vœf f Vol. 14, No. 1

46 já g Á hœá f Table 8. d f d vf i [ e : e] 1997 1998 1999 2000 2001 jdˆ v 1,976 3,012 3,263 5,238 5,674 l, j, Œ, z, zƒ l, Œ ƒ f 6,723 5,325 6,870 9,202 11,254 f h, x, ƒ, f g d hf 4,747 2,313 3,607 3,964 5,580 f vs : Š f Œ Š ff f l f. f ƒ f Š x l Š, f 80% f vœf Š Œf d f utf hˆf. ˆf ˆ h gf Lester M. Crawford ƒ if h e if f f x Š f d f f. f hˆ df ff Š vœf Š f Š f f Œ. ƒ ff f l f f Š f g f f x Š f d f. g f f x Š eš f e f h Š Œ f f lh h Š hh f f f Š d Œf h w. f x j ~} f f ƒ(guidant) fš f ƒ hˆf Œff ~ e f f Š l f Š f Œ Œ f Š h ƒ fš. f h Œf w d. f ƒ d s tl ff Š f Š f, ƒ f h Œ f Œh f vœf e Š f f Š fdš Œhf h Š. ˆf ˆ h f f ƒ fš f Š h x e f lš f f. wf ŠŠ f 45 f e vœf Š f j Š f f 581 f Œf f f ƒ f f ŠŠ. d ƒ hˆf Š, Œf jf 92% h f f hf f f ~. fš Š f f Š, if f Š f f Œf f d 30f ~ f, vœ g f f Š l f 15%f ƒ f f f Œf f d f Š Š lf ~ f 10%f f ~. Š ƒ fšl 2 f Š ef Œ f f h eœš h. g ˆf ˆ h f f ƒ f Œf f f ƒ f h Š, ƒ f Š vœf Š g hf f l Š ŠŠ f d Š f. f d Š 20 h f Œf f hh f f v f. g a. vf ƒ f hˆ f Šd Š g ff f. Œ Œ hh Œ, Œ Œ f Œf f Œ, glœ f h f Œff 25% f l Š f. ƒ gf g f if ˆ f g g f ŠŠ 30% f f l ef f. d ƒ ŠŠ f d f ihf w hf j l l Š Š j f. f l f f u 21 f f d f h h Š f Œ hf f Š x f f. ƒ ŠŠ f d gf g f vf Œ f. f Š gf f hˆ ŠŠ Œ gf ƒ f f t f jf hr ŒŠ f f Š. Table 8 f l l jd fˆ f f l h f rlš f. 2004 ƒ d f 2 f, x d ƒ 250 e f hf Š 5 e f gf. Š, g ƒ gf gef if ˆ f g g f ŠŠ 30% f gf f f, hh Œ f Œ Œf Œ Œ Œ Œ f f glœ Œff 25% f l Š f v Š ƒ gf gef hf l Š f l. b. jd hˆ Œ ef f f h fš f d ƒ hˆf hiš t l f,,, ff ff, d ƒf Œ 2005 1e ut Biomaterials Research 2010

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