ZAŠTO JE KAROTIDNA ENDARTEREKTOMIJA METOD IZBORA U LEČEWU STENOZE KAROTIDNIH ARTERIJA?

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1 PREGLEDI LITERATURE BIBLID: , 136(2008) Suppl 2, p ZAŠTO JE KAROTIDNA ENDARTEREKTOMIJA METOD IZBORA U LEČEWU STENOZE KAROTIDNIH ARTERIJA? Đorđe RADAK 1, Lazar DAVIDOVIĆ 2 1 Klinika za vaskularnu hirurgiju, Institut za kardiovaskularne bolesti Dediwe, Beograd; 2 Klinika za vaskularnu hirurgiju, Institut za kardiovaskularne bolesti, Klinički centar Srbije, Beograd KRATAK SADRŽAJ U l e č e wu s t en oz a n tn o - o k l uz i vn e b ol e s t i k ar o t i d n i h a r t e r i j a p r i m e wu j u se: e n d a r t e r e k t o m i j a, p e r k u t a n a t r a n - sluminalna angioplastika (PTA) s ugrad wom sten ta, re sek ci ja i in ter po zi ci ja graf ta i baj pas-po stu pak. Pr va dva postup ka su in di ko va na kod seg ment nih le zi ja, ko je su mno go če šće, dok se dru ga dva pri me wu ju ako su le zi je du že i ako u v e ć oj m er i z ah v at aj u z aj e dn ičk u k ar ot i dn u a rt er i j u. J e d n a o d gl a v n i h d i l e m a p r e t ho d n i h go d i n a b i l a j e: d a l i p r i - me ni ti karotidnu endarterektomiju ili PTA sa sten tom? Bez ob zi ra na eks pan zi ju pri me ne PTA sa sten tom ka ro tid - n e a r t er ij e, r an i i n ar oč it o ud aq en i r ez ult at i p r e d n o s t d a j u e n d a r t e r e k t o m i j i. I s t o v r e m e n o, PTA i ugrad wa stenta pred stavqaju daleko skupqi postupak. Oba meto da i ka ro tid na en dar te rek to mi ja i PTA s ugrad wom sten ta imaju značajno i defi ni sa no me sto u le če wu seg ment nih ste no zant no -okluzivnih lezija karotidnih arteri ja. Oboqe - wa sr ca, pluća i bubrega koja čine rizičnijima hi rur ške za hva te u op štoj en do tra he al noj ane ste zi ji ni su ap so lutna in dikacija za primenu PTA i stenta karotidnih ar te ri ja, jer se en dar te rek to mi ja mo že iz ve sti u uslo vi ma cer - vik snog bloka. Glavne indikacije za PTA s ugrad wom sten ta su: hi rur ški te ško pri stu pač ne ili ne pri stu pač ne le zij e (i z n a d n iv o a d rug o g c e rv i ks n o g p rš q en a i l i i s p o d n i v o a k l a v i k u l e), l e z i j e ko j e s u p o s l e d i c a i r a d i j a c i o n o g a r - t e r i t i s a, l ez ij e k ar ot i dn i h a rt er ij a koj e s u u r eg i o n u v e l i ko g h i ru r š ko g o ž i q k a i k a s n e p o n o v n e s t e n o z e e n d a r t e - r e k t o m is an i h k ar ot i dn i h a rt er ij a. Kqučne reči: karotidna endarterektomija; PTA; stent UVOD Cerebrovaskularne bolesti (CVB) imaju ogroman medicinski i socijalno-ekonomski značaj, posebno u zemqama koje su krajem dvadesetog veka ušle u fazu tzv. tranzicije, ukqučujući i našu. Konkretno, u Sjediwenim Američkim Državama, Kanadi, Švajcarskoj, Francuskoj i Australiji godišwa učestalost CVB mawa je od 100 obolelih na muškaraca, odnosno 70 obolelih na žena. U zemqama istočne Evrope i bivšeg SSSR u periodu godine učestalost CVB je na godišwem nivou bila obolelih muškaraca na , odnosno obolele žene na [1]. U istom periodu u istočnoevropskim zemqama i bivšoj Jugoslaviji zabeleženo je povećawe smrtnosti od CVB [2, 3]. Od do godine smrtnost od CVB je činila 14% od ukupnog mortaliteta. Pretpostavqa se da u našoj zemqi od posledica CVB izazvanih oboqewem ekstrakranijalnog dela karotidnih arterija godišwe umre oko pet hiqada qudi [4]. Hirurško lečewe karotidnih arterija, koje bi ove posledice trebalo da spreči, na izvestan način je delikatnije od ostalih vaskularnih rekonstruktivnih postupaka, imajući u vidu indikacije, hiruršku tehniku i taktiku [5, 6]. Danas se smatra da se karotidnom hirurgijom mogu baviti samo oni centri u kojima je ukupan rani mortalitet i morbiditet od asimptomatskih lezija mawi od 1,5%, od simptomatskih mawi od 3%, a od kontralateralne okluzije mawi od 7% [5, 6]. KAROTIDNA ENDARTEREKTOMIJA ILI PERKUTANA TRANSLUMINALNA ANGIOPLASTIKA S UGRADWOM STENTA? U lečewu stenozantno-okluzivne bolesti karotidnih arterija primewuju se: endarterektomija (CEA), perkutana transluminalna angioplastika s ugradwom stenta (PTA sa stentom), resekcija i interpozicija grafta i bajpas-postupak [4]. Prva dva postupka su indikovana kod segmentnih lezija, koje se javqaju mnogo češće, a druga dva ako su lezije duže i ako u većoj meri zahvataju zajedničku karotidnu arteriju. Jedna od glavnih dilema prethodnih godina bila je: da li segmentnu stenozantno-okluzivnu leziju karotidne arterije lečiti primenom CEA ili PTA sa stentom? Rani rezultati najvećih studija objavqenih posledwih deset godina prikazani su u tabeli 1. Podaci iz ove tabele nedvosmisleno pokazuju prednosti everzione nad konvencionalnom CEA ako se imaju u vidu mortalitet i CVB tokom prvih sedam dana od operacije. Prvi rezultati primene PTA karotidne arterije objavqeni su godine [18]. Ovaj postupak je posledwih deset godina doživeo veliku ekspanziju, ali rani rezultati se nisu mogli meriti s hirurškim. To je pokazala i prva multicentrična studija CA VA TAS (Ca ro tid and Ver te bral Ar tery Tran slumi nal An gi o plasty Study) [19], koja je obuhvatila 251 bolesnika kod kojeg je od do godine primewena PTA karotidnih arterija s ugradwom stenta. Ukupan rani postoperacioni mortalitet i morbiditet od čak 10% bio je neprihvatqivo veliki [18]. (Čak i 181

2 TABELA 1. Rane komplikacije (smrtnost i CVB u prvih sedam dana od operacije) konvencionalne i everzione karotidne endarterektomije u drugim studijama. TABLE 1. Early complications (mortality and stroke during the first seven postoperative days) following conventional and eversion carotid endarterectomy in other studies. Autor i godina Author and year Broj bolesnika Number of patients Operisani sa KKE Operisani sa EKE With CCE With ECE Rani smrtni ishod Early death KKE EKE CCE ECE Darling et al; 1996 [7] % 1.1% NS Entz et al; 1997 [8] % 0.54% <0.05 Cao et al; 1997 [9] % 0.7% S Cao et al; 1998 [10] % 1.3% NS Shah et al; 1998 [11] % 1.02% S Ballotta et al; 1999 [12] % 0.0% =0.003 Peiper et al; 1999 [13] % 1.1% =0.59 Radak et al; 2000 [14] /682 10/2124 =0.038 Katras et al; 2001 [15] % + 2.8% 0.8% NS Littoy et al; 2004 [16] % 0.0% NS Marković; 2006 [17] % 1.0% =0.359 KKE konvencionalna karotidna endarterektomija; EKE everziona karotidna endarterektomija; NS nije statistički značajno; S statistički značajno CCE conventional carotid endarterectomy; ECE eversion carotid endarterectomy; NS not statistically significant; S statistically significant p TABELA 2. Rane komplikacije (smrtnost i CVB u prvih sedam dana od operacije) primene PTA i stenta karotidnih arterija u drugim studijama. TABLE 2. Early complications (mortality and stroke during the first seven postoperative days) following carotid PTA and stenting in other studies. Autor/studija i godina Author/study and year Broj bolesnika Number of patients Mortalitet i morbiditet Mortality and morbidity CAVATAS; 2001 [19] % Kastrup et al; 2003 [20] % Cremonisi et al; 2003 [21] % Becquemin et al; 2003 [22] % Dabrowski et al; 2003 [23] % Cernetti et al; 2003 [24] % Bush et al; 2003 [25] % Gable et al; 2003 [26] % Lal et al; 2003 [27] % kod okluzije kontralateralne karotidne arterije najveći dopušten ukupni rani postoperacioni mortalitet i morbiditet CEA mora biti mawi od 7%.) Razlog ovako loših rezultata bio je u izostanku moždane zaštite. Obavezna primena zaštite (sprečavawe distalne embolizacije) tokom PTA karotidnih arterija i ugradwe stenta posledwih godina značajno je poboqšala rezultate (Tabela 2) [20-27]. Bez obzira na to, posebno kada je u pitawu everzioni metod, CEA je i daqe praćena nižom stopom ranog postoperacionog mortaliteta i centralnog neurološkog morbiditeta. Naime, posle ukupno slučajeva primene PTA karotidnih arterija s ugradwom stenta u periodu godine, ukupna rana smrtnost posle hirurškog lečewa i centralna neurološka stopa smrtnosti bile su 4,7% [28]. Ovaj statistički podatak dodatno dobija na značaju ako se u TABELA 3. Kasne ponovne stenoze posle konvencionalne i everzione karotidne endarterektomije u drugim studijama. TABLE 3. Long-term restenosis following carotid endarterectomy in other studies. Autor i godina Author and year Broj bolesnika Number of patients Operisani sa KKE Operisani sa EKE With CCE With ECE Period nadgledawa Follow-up period Kasne ponovne stenoze Late restenosis KKE EKE CCE ECE Cao et al; 1997 [9] m 6.9% 2.2% =0.03 Cao et al; 1998 [10] m 4.1% 2.4% =0.08 Shah et al; 1998 [11] m 1.1% 0.3% S Ballotta et al; 1999 [12] m 1.2% 0.0% S Peiper et al; 1999 [13] m 10.2% 2.5% S Radak et al; 2000 [14] % 0.5% =0.006 Cao et al; 2000 [29] 33 m 9.2% 3.6% S Katras et al; 2001 [15] m 6.5% 1.7% <0.05 Littoy et al; 2004 [16] m 4.88% 3.13% S Ballotta et al; 2004 [30] y 0.6% 0.5% S Marković; 2006 [17] ±14.3 m 6.1% 0.0% >0.05 KKE konvencionalna karotidna endarterektomija; EKE everziona karotidna endarterektomija; S statistički značajno; m meseci; y godine CCE conventional carotid endarterectomy; ECE eversion carotid endarterectomy; S statistically significant; m months; y years p 182

3 obzir uzme čiwenica da studije o primeni CEA obuhvataju mnogo veći broj ispitanika. Prednosti everzione CEA još više dolaze do izražaja ako se upoređuju udaqene ponovne stenoze posle we (Tabela 3), odnosno PTA i stenta karotidnih arterija (Tabela 4). I u ovom slučaju velike studije hirurški lečenih bolesnika ukqučile su značajno veći broj ispitanika, koji su i mnogo duže nadgledani. U tabeli 5 sažeto su prikazani rani i udaqeni rezultati primene oba metoda. Kao što se uočava, prednost ima hirurški metod. TABELA 4. Kasne ponovne stenoze posle primene PTA i stenta karotidnih arterija u drugim studijama. TABLE 4. Long-term re-stenosis following carotid PTA and stenting in other studies. Autor/studija i godina Author/study and year Broj Period bolesnika nadgledawa Number of Follow-up patients period Ponovna stenoza Restenosis CAVATAS; 2001 [19] m 14.0% Roubin et al; 2001 [31] m 3.1% Criado et al; 2002 [32] m 3.0% Dabrowski et al; 2003 [23] m 7.5% Becquemin et al; 2003 [22] m 7.5% Wholey et al; 2003 [33] m 8.0% DeBorst et al; 2003 [34] m 1.8% Lal et al; 2003 [27] m 6.4% Bush et al; 2003 [25] m 2.0% Bowser et al; 2003 [35] m 16.0% m meseci m months U literaturi su opisane kako rane, tako i kasne konverzije PTA sa stentom u hirurško lečewe [38]. Glavni nedostatak ovakvog načina poređewa pomenutih metoda jeste u tome što su postupci izvođeni u različitim uslovima i periodima, odnosno što nisu randomizirani. Zbog toga poseban značaj ima nedavno objavqena multicentrična, randomizirana studija koja je upoređivala rane rezultate i komplikacije (u prvih trideset dana od operacije) kod 259 bolesnika kojima je urađena CEA i 261 bolesnika kod kojeg je primewen PTA karotidnih arterija s ugradwom stenta (Tabela 6) [39]. Ova studija je nedvosmisleno pokazala da je CEA praćena statistički značajno nižom stopom nefatalnih CVB (2,7% prema 8,8%), smrtnih ishoda (1,2% prema 0,8%), TIA (0,8% prema 2,3%) i ukupnog broja smrtnih ishoda i CVB (3,9% prema 9,6%) u odnosu na PTA sa stentom [39]. Ništa mawe nije značajan ni ekonomski aspekt oba metoda. Jedna od prednosti PTA koronarnih ili perifernih arterija je i skraćewe boravka u bolnici. To značajno smawuje ukupne troškove lečewa, posebno u visokorazvijenim zemqama, gde je bolničko lečewe skupo. Kod primene PTA karotidnih arterija s ugradwom stenta, ta razlika ni približno nije tako značajna. Naime, bolničko lečewe bolesnika kod kojeg je primewena CEA traje dva-tri dana, a ako je rađena PTA sa stentom, boravak u bolnici traje svega dan-dva. S druge strane, cena stenta i potrošnog materijala potrebnog za izvođewe PTA i wegovu ugradwu u karotidnu arteriju je evra i skoro deset puta je veća od cene primene CEA. TABELA 5. Poređewe ranih i udaqenih rezultata karotidne endarterektomije i PTA karotidnih arterija. TABLE 5. The comparison of early and long-term results following carotid endarterectomy and carotid PTA with stenting. Parametar Parameter Everziona endarterektomija Eversion endarterectomy PTA s ugradwom stenta PTA with stenting Mortalitet i morbiditet Mortality and morbidity Referenca Reference Kasna ponovna stenoza Late restenosis Referenca Reference % [7-17, 36, 37] % [9-17, 29, 30, 36, 37] % [19-27] % [19, 23, 25, 27, 31-35] TABELA 6. Endarterektomija ili PTA sa stentom karotidnih arterija: rezultati multicentrične, prospektivne, randomizirane studije Radaka i saradnika [37]. TABLE 6. Carotid endarterectomy versus carotid PTA and stenting: the results of a multicentric, prospective, randomized study by Radak et al [37]. Parametar Parameter Nefatalna CVB Nonfatal stroke Smrt Death Fatalna CVB Fatal stroke Ostali uzroci Other cause Prolazni ishemijski napad TIA Smrt i CVB Death and stroke Endarterektomija Endarterectomy (N=259) N broj bolesnika; RR relativni rizik; CI interval poverewa N number of patients; RR relative risk; CI confidence interval PTA s ugradwom stenta PTA with stenting (N=261) RR (95% CI) 7 (2.7%) 23 (8.8%) 3.3 ( ) (0.8%) 0.7 ( ) (0.4%) 1 (0.4%) 2 (0.8%) 6 (2.3%) 3.0 ( ) (3.9%) 25 (9.6%) 2.5 ( ) 0.01 p 183

4 Izvođewe CEA je teže i praćeno je lošijim ranim rezultatima kod sekundarnih operacija zbog kasne ponovne stenoze, kada je stenoza karotidnih arterija posledica iradijacionog arteritisa, odnosno ako je bolesniku na istoj strani vrata već rađena neka hirurška intervencija [27, 28, 30, 33-35]. CEA je teško ili čak nemoguće izvesti ako je lezija teško pristupačna iznad nivoa drugog cerviksnog pršqena ili ispod klavikule (Slika 1) [28, 33-35]. PTA i stent karotidnih arterija ne treba ni pokušavati primeniti kada bolesnik ima: tešku perifernu okluzivnu vaskularnu bolest (što onemogućava endoluminalni pristup karotidnoj arteriji), tešku aortnu stenozu, značajnu hroničnu slabost bubrega, anomalije luka aorte, pridružen tortuozitet, SLIKA 3. Kontraindikacije za primenu PTA i ugradwu stenta karotidne arterije. A. Teška stenoza unutrašwe karotidne arterije s pridruženom elongacijom (bela strelica); B. Kritična stenoza unutrašwe karotidne arterije (>99%) duža od 2 cm (crna strelica); C. Teška kalcifikovana stenoza unutrašwe karotidne arterije (crna strelica). FIGURE 3. Contraindications for carotid angioplasty and stenting. A. Severe internal carotid artery stenosis associated with elongation (white arrow); B.Critical (>99%) stenosis longer than 2 cm (white arrow); C. Severely calcified stenosis of the internal carotid artery (black arrow). tzv. kinking ili kojling karotidnih arterija, pridruženu aneurizmu karotidne arterije, stenozu karotidne arterije dužu od 2 cm, stenozu karotidne arterije veću od 99%, kalcifikovanu stenozu karotidne arterije ili neorganizovan tromb u karotidnoj arteriji (Slike 2 i 3) [28, 38-43]. SLIKA 1. Indikacije za primenu PTA i ugradwu stenta karotidnih arterija. A. Proksimalna stenoza leve zajedničke karotidne arterije (bela strelica); B. Značajna kasna ponovna stenoza posle karotidne endarterektomije (bela strelica). FIGURE 1. Indications for carotid angioplasty and stenting. A. Proximal stenosis of the left common carotid artery (white arrow); B. Significant late restenosis following carotid endarterectomy (white arrow). ZAKQUČAK Oba metoda i CEA i PTA s ugradwom stenta imaju veoma važno mesto u lečewu segmentnih stenozantno-okluzivnih lezija karotidnih arterija. Oboqewa srca, pluća i bubrega koja čine rizičnijima hirurške zahvate u opštoj endotrahealnoj anesteziji nisu apsolutna indikacija za primenu PTA karotidnih arterija i ugradwu stenta, jer se CEA može izvesti u uslovima cerviksnog bloka. Glavne indikacije za primenu PTA i stenta su: hirurški teško pristupačne ili nepristupačne lezije (iznad nivoa drugog cerviksnog pršqena ili ispod nivoa klavikule), lezije koje su posledica iradijacionog arteritisa, lezije koje su u regionu velikog hirurškog ožiqka od drugih ranijih hirurških postupaka i kasne ponovne stenoze posle urađene CEA. SLIKA 2. Kontraindikacije za primenu PTA i ugradwu stenta karotidne arterije. A. Anomalije luka aorte: crna strelica pokazuje da desna zajednička karotidna arterija polazi zajedno s levom; B. Crna strelica pokazuje težak tortuozitet desne zajedničke karotidne arterije. FIGURE 2. Contraindications for carotid angioplasty and stenting. A. Unfavourable aortic arch anatomy: black arrow shows common origin of the common right and left carotid artery; B. Black arrow shows severe tortuosity of the right common carotid artery. LITERATURA 1. Sarti C, Rastenyte D, Cepaitis Z, Tuomilehto J. International trends in mortality from stroke, 1968 to Stroke 2000; 31: Menotti A, Jacobs DR, Blackburn H, et al. Twenty-five-year prediction of stroke deaths in the seven countries study the role of blood pressure and its changes. Stroke 1996; 27: Ryglewicz D, Polakowska M, Lechowicz W, et al. Stroke mortality rates in Poland did not decline between 1984 and Stroke 1997; 28:

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Immediate reoperation for perioperative stroke after 2250 carotid endarterectomies: Differences between intraoperative and early postoperative stroke. J Vasc Surg 1999; 30: Faggioli GL, Ferri M, Rossi C, Garguilo M, Freyrie A, Stella A. Carotid stent failure: Results of surgical rescue. Eur J Vasc Endovasac Surg 2007; 33(1): Mas JL, Chatellier G, Beysssen B, et al. Endarterectomy versus Stenting in patients with symptomatic severe carotid stenosis. N Engl J Med 2006; 355: Setacci C, Cremonesi A. SPACE and EVA-3S trials: the need of standards for carotid stenting. Eur J Vasc Endovasac Surg 2007; 33(1): Davidović L, Sinđelić R, Jovanović Z, Božić V, Marković D. Takayasu s aortoarteritis. Acta Chir Iug 2005; 51(3): Davidovic L, Kostic D, Maksimovic Z, et al. Carotid artery aneurysms. Vascular 2004; 12(3): Radak Dj, Davidović L, Vukobratov V, et al. Carotid artery aneurysms: Serbian multicentric study. Ann Vasc Surg 2007; 21(1):

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