abcArquivos Brasileiros de CardiologiaArq. Bras. Cardiol.0066-782X1678-4170Sociedade Brasileira de Cardiologia - SBCSão Paulo, SP, Brazil8CBxgZHKzrrMTX7WpsjDkSt00001S0066-782X2006000400001S0066-782X(06)0860040110.1590/S0066-782X2006000400001EditorialStents com eluição de sirolimus para tratamento de estenose em artérias coronárias de pequeno calibre: o que aprendemos?CostaRicardo A.LanskyAlexandra J.Nova YorkNYColumbia University Medical CenterCardiovascular Research Foundation USA042006864245248This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.25042006
EDITORIAL
Stents com eluição de sirolimus para tratamento de estenose em artérias coronárias de pequeno calibre: o que aprendemos?
Ricardo A. Costa, MD; Alexandra J. Lansky, MD
Cardiovascular Research Foundation and Columbia University Medical Center - Nova York, NY, USA
Correspondência
A intervenção coronariana percutânea (ICP) em vasos de pequeno calibre (definida de maneira ampla como estenose em vaso com diâmetro de referência inferior a 2,75-2,80 mm ou 3,00 mm)1,2 tem sido historicamente associada a altas taxas de reestenose (18-52%) e revascularização do vaso (até 27%)1,3-5. Antes do advento dos stents revestidos com medicamentos, havia uma forte relação entre reestenose e calibre do vaso, com uma associação inversa entre o calibre do vaso e reestenose angiográfica, atribuída à quantidade desproporcionalmente maior de hiperplasia neointimal (HNI) em relação ao calibre dos pequenos vasos1,3. Esse fenômeno parecia ser agravado em diabéticos, que muitas vezes apresentam artérias "pequenas" em virtude de doença coronariana difusa e exagerada resposta proliferativa neointimal4. Diversos estudos tentaram demonstrar a eficácia do implante de endopróteses em comparação com angioplastia transluminal coronariana (ATC) por balão em vasos de pequeno calibre, mas os resultados foram controversos. Entretanto, uma recente metanálise de 11 estudos clínicos randomizados (2.971 pacientes) comparou o uso de stents não-revestidos com ATC por balão em vasos de 2,22 a 2,60 mm, e os resultados demonstraram que o implante de endoprótese reduziu a reestenose (p = 0,003), com risco relativo de 0,77 (IC 95% 0,65, 0,92)1.
Com a introdução dos stents revestidos com sirolimus, muitos esperavam que a sua eficácia na prevenção de reestenose em lesões não-complicadas fosse estendida para subgrupos de alto risco, como vasos pequenos. Em seu artigo para os Arquivos Brasileiros de Cardiologia, Devito e cols.6 relataram os resultados obtidos com 80 pacientes incluídos em um estudo prospectivo não-randomizado que comparou o stent revestido com sirolimus (Cypher®) com um stent não-revestido (Multi-Link Pixel®) no tratamento de lesões coronarianas primárias em vasos de 2,20 a 2,75 mm de diâmetro. Todas as endopróteses foram implantadas com sucesso, e as dimensões finais da luz foram semelhantes nos dois grupos. (É importante observar que, nessa investigação, os pacientes foram incluídos consecutivamente em dois momentos distintos, e embora os dados clínicos e demográficos iniciais fossem compatíveis, os dois grupos não eram totalmente homogêneos em relação a alguns critérios importantes, como complexidade da lesão e tamanho da endoprótese). No acompanhamento, perda tardia da luz (PTL), reestenose e área de hiperplasia neointimal (HNI) foram reduzidas significativamente com o emprego de stent com sirolimus; além disso, houve redução de 3,5 vezes na revascularização da lesão-alvo (RLA) com o uso de stent com sirolimus em comparação com stent comum, diferença essa que não alcançou significância estatística.
O desempenho do stent com sirolimus em "vasos pequenos" foi avaliado em vários estudos clínicos randomizados e registros (tab. 1). A PTL, um substituto da hiperplasia neointimal, foi reduzida de forma significativa com o uso de stent com sirolimus em vasos pequenos comparado com o stent comum, ficando em 98,7%, 78,8%, 81%, 88,2% e 82,2% nos estudos RAVEL, SIRIUS, E-SIRIUS, C-SIRIUS e SES-SMART, respectivamente2,5,7-10. No estudo de Devito, a PTL foi reduzida em 77,5%, p < 0,0016. No SIRIUS-2.25, a PTL intra-stent foi ligeiramente mais elevada (0,36 mm) do que nos outros estudos (0,01-0,21 mm) (tab. 1). As porcentagens de diabéticos (40%) e lesões complexas (B2/C) desse estudo eram maiores11. Os pacientes diabéticos tem demonstrado apresentar maior PTL do que os não-diabéticos12,13. Na análise de Devito, que também tinha 40% de diabéticos porém lesões menos complexas, a PTL foi de 0,25 mm6. De modo geral, as PTL foram comparáveis às das lesões em vasos de maior diâmetro tratados com stents revestidos com sirolimus7-9,14 e consideravelmente menores do que as dos stents comuns (0,80-1,05 mm)2,5,7,10, confirmando a regularidade e eficácia dos stents com sirolimus na prevenção de HNI, apesar das diferenças relativas à porcentagem de pacientes diabéticos, ao calibre do vaso e às características da lesão.
A clássica relação inversa entre calibre do vaso e reestenose não foi observada com o uso de stents com sirolimus no estudo RAVEL (0% de reestenose em todos os diâmetros de vaso)7. Entretanto, em uma subanálise do estudo SIRIUS (em que as lesões eram mais extensas e mais complexas), as lesões foram divididas em tercis de acordo com o calibre do vaso, e a porcentagem de reestenose intra-stent foi de 5%, 2,5% e 1,9% com o uso de stent com sirolimus em vasos pequenos (2,32 mm), médios (2,78 mm) e grandes (3,31 mm). Da mesma forma, a porcentagem de reestenose no segmento do vaso-alvo foi maior em vasos pequenos (17,6%), em comparação com vasos médios (6,6%) e grandes (1,9%)9. Conseqüentemente, as reduções de risco de reestenose no segmento do vaso-alvo com o uso de stent com sirolimus caíram para 93,7%, 81,7% e 58,8% em vasos grandes, médios e pequenos, respectivamente. As taxas de reestenose do SIRIUS-2.25 foram comparáveis às do tercil de "vasos pequenos" do SIRIUS e associadas com comprimento da endoprótese, diabetes e número de próteses implantadas11. No artigo de Devito, houve 0% de reestenose intra-stent e apenas 4% de reestenose no segmento do vaso-alvo com stents com sirolimus, comparado com 33,3% de reestenose intra-stent e 36,7% de reestenose no segmento do vaso-alvo com o emprego de stent comum (p < 0,001)6. Resultados semelhantes foram encontrados nos estudos RAVEL, E-SIRIUS, C-SIRIUS e SVELTE5,7,10,15. No RESEARCH, o calibre do vaso era consideravelmente menor do que nos outros estudos (tab. 1), e os casos de reestenose (apenas intra-stent) ocorreram principalmente após o tratamento de lesões ostiais14. É importante ressaltar que, na subanálise de diabéticos do SES-SMART, o stent com sirolimus foi associado com redução significativa de PTL e reestenose, em comparação com o stent comum; entretanto, quando apenas os pacientes insulino-dependentes foram levados em consideração (35%), a taxa de reestenose com o uso de stent com sirolimus subiu para 40%12. Esses dados levam às seguintes considerações em relação ao uso de stent com sirolimus em vasos pequenos: 1) as taxas de reestenose nos vasos pequenos são mais elevadas do que nos vasos de maior calibre; 2) a reestenose parece aumentar de acordo com a gravidade da lesão e área coberta pela endoprótese; 3) pacientes diabéticos apresentam taxas mais altas de reestenose. Talvez isso se deva não apenas à resposta vascular hiperproliferativa e agressiva observada com freqüência, mas também ao implante sub-otimo do stent (cobertura incompleta da lesão e expansão insuficiente do stent), uma vez que os diabéticos muitas vezes apresentam lesões longas e difusas (como foi mencionado anteriormente); e 4) a taxa mais elevada de reestenose "no segmento do vaso-alvo" (comparado com reestenose "intra-stent") encontrada na maioria dos estudos (tab. 1) pode ser conseqüência de cobertura incompleta da lesão e/ou segmento lesado durante a realização de intervenção coronariana percutânea. Esses problemas foram identificados por alguns autores8,16. Para a obtenção de melhores resultados com vasos pequenos é essencial o aprimoramento das técnicas de aplicação dos "stents com eluição de medicamento" – reduzindo ao mínimo o trauma da área lesada com o emprego de balões curtos de pré-dilatação, cobrindo toda a lesão/segmento lesado, usando balões curtos para a pós-dilatação (posicionados no interior da área coberta para evitar lesão além das bordas dos stents) e efetuando uma aposição completa, no caso de múltiplas próteses, evitando falhas.
Estudos anteriores realizados com a utilização de ultra-som intracoronariano (USIC) demonstraram que o diâmetro luminal final em vasos com menos de 2,75 mm prevê a necessidade de revascularização17. Resultados semelhantes foram encontrados com o uso de stents com sirolimus. No subestudo de USIC do SIRIUS, constatou-se que uma área luminal mínima final intra-stent superior a 4,5 mm2 em vasos com menos de 2,8 mm de diâmetro (por ACQ) representava um limiar que previa uma luz "adequada" pelo USIC no acompanhamento (>4,0 mm2). O valor preditivo positivo das dimensões do stent pelo USIC foi de 90%18. Além disso, Takebayashi e cols. relataram uma série de pacientes com falência no vaso-alvo após implante de stent com sirolimus, a maioria (especialmente reestenose intra-stent) associada com subexpansão do stent19. Isso era esperado, pois, uma vez que um medicamento que se mostrou eficaz (nesse caso, o sirolimus) inibiu a maior parte da hiperplasia neointimal (tab. 1), a principal causa de reestenose intra-stent passou a ser a subexpansão da endoprótese. Por fim, uma porcentagem maior de área da placa e uma área maior de borda do stent/área luminal mínima de referência foi associada com estenose da borda no grupo de stent com sirolimus do estudo SIRIUS20. Essas evidências indicam que a eficácia do stent com sirolimus depende da capacidade da prótese de impedir a formação de HNI e de uma técnica de aplicação perfeita. No contexto dos vasos de pequeno calibre, a realização de ICP guiada por USIC para a colocação de stents com sirolimus deve ser levada em consideração e até mesmo recomendada, pois apresenta algumas vantagens: 1) permite a avaliação precisa do diâmetro do vaso e da extensão da lesão antes do procedimento, o que ajuda os operadores a selecionarem a técnica e o dispositivo apropriados para a cobertura total da lesão e o emprego de um stent de tamanho adequado; 2) ajuda a identificar uma expansão inadequada do stent, permitindo que o operador dilate posteriormente a endoprótese para obter a expansão ideal.
Finalmente, o implante de stents com sirolimus em vasos pequenos tem sido associado com altas taxas de sucesso (> 95%) e segurança (comparáveis à de vasos maiores tratados com esses stents), refletindo-se na baixa incidência de trombose intra-stent e eventos clínicos adversos maiores no acompanhamento de médio e longo prazo (tab. 1)2,5,6,8,10,11,14,15. Além disso, o stent com sirolimus levou a uma redução relativa de 70% a 81% da RLA comparado com o stent comum em estudos clínicos randomizados de "pequenos vasos"2,5,10. Um fato importante é que as taxas de RLA e eventos clínicos adversos maiores (tab. 1) foram extraordinariamente baixas em todos os estudos (< 10%), sobretudo levando-se em consideração as lesões de alto risco e as populações de alto risco tratadas. Esses resultados confirmam o enorme impacto e os benefícios gerais do stent com sirolimus em comparação com stent comum e os importantes controles com ICP em vasos pequenos. No entanto, apesar do enorme avanço alcançado nessa área, o vaso de pequeno calibre ainda está associado com a ocorrência de reestenose após o implante de stent com sirolimus8. Portanto, ainda são necessários esforços no sentido de melhorar os resultados, como aprimoramento da técnica de aplicação dos stents e desenvolvimento de novas tecnologias específicas para vasos pequenos.
REFERÊNCIAS
1. Moreno R, Fernandez C, Alfonso F, Hernandez R, Perez-Vizcayno MJ, Escaned J et al. Coronary stenting versus balloon angioplasty in small vessels: a meta-analysis from 11 randomized studies. J Am Coll Cardiol. 2004;43:1964-72.
2. Ardissino D, Cavallini C, Bramucci E, Indolfi C, Marzocchi A, Manari A et al. Sirolimus-eluting vs uncoated stents for prevention of restenosis in small coronary arteries: a randomized trial. Jama. 2004;292:2727-34.
3. Holmes DR Jr, Kereiakes DJ. The approach to small vessels in the era of drug-eluting stents. Rev Cardiovasc Med. 2005;6 Suppl 1:S31-7.
4. Saucedo JF, Popma JJ, Kennard ED, Talley JD, Lansky A, Leon MB et al. Relation of coronary artery size to one-year clinical events after new device angioplasty of native coronary arteries (a New Approach to Coronary Intervention [NACI] Registry Report). Am J Cardiol. 2000;85:166-71.
5. Schampaert E, Cohen EA, Schluter M, Reeves F, Traboulsi M, Title LM et al. The Canadian study of the sirolimus-eluting stent in the treatment of patients with long de novo lesions in small native coronary arteries (C-SIRIUS). J Am Coll Cardiol. 2004;43:1110-5.
6. Devito FS, Sousa AGMR, Feres F, Abizaid A, Staico R, Mattos LAP et al. Comparative Analysis of Intimal Hyperplasia After Sirolimus-Eluting Stent and Thin-Strut Bare Metal Stent Implantation in Small Coronary Arteries. Arq Bras Cardiol. 2006;86:268-75.
7. Regar E, Serruys PW, Bode C, Holubarsch C, Guermonprez JL, Wijns W et al. Angiographic findings of the multicenter Randomized Study With the Sirolimus-Eluting Bx Velocity Balloon-Expandable Stent (RAVEL): sirolimus-eluting stents inhibit restenosis irrespective of the vessel size. Circulation. 2002;106:1949-56.
8. Moses JW, Leon MB, Popma JJ, Fitzgerald PJ, Holmes DR, O'Shaughnessy C et al. Sirolimus-eluting stents versus standard stents in patients with stenosis in a native coronary artery. N Engl J Med. 2003;349:1315-23.
9. Popma JJ, Leon MB, Moses JW, Holmes DR Jr, Cox N, Fitzpatrick M et al. Quantitative assessment of angiographic restenosis after sirolimus-eluting stent implantation in native coronary arteries. Circulation. 2004;110:3773-80.
10. Schofer J, Schluter M, Gershlick AH, Wijns W, Garcia E, Schampaert E et al. Sirolimus-eluting stents for treatment of patients with long atherosclerotic lesions in small coronary arteries: double-blind, randomised controlled trial (E-SIRIUS). Lancet. 2003;362:1093-9.
11. Nikolsky E, Moses JW, Cambier P, Bachinsky B, O' Shaughnessy C, Mehran R et al. Results from the 2.25mm Sirolimus-Eluting BS Velocity Stent Registry in Patients with Native Coronary Artery Lesions. Am J Cardiol. 2005;96 (Suppl 7A):179H.
12. Ortolani P, Ardissino D, Cavallini C, Bramucci E, Indolfi C, Aquilina M et al. Effect of sirolimus-eluting stent in diabetic patients with small coronary arteries (a SES-SMART substudy). Am J Cardiol. 2005;96:1393-8.
13. Moussa I, Leon MB, Baim DS, O'Neill WW, Popma JJ, Buchbinder M et al. Impact of sirolimus-eluting stents on outcome in diabetic patients: a SIRIUS (SIRolImUS-coated Bx Velocity balloon-expandable stent in the treatment of patients with de novo coronary artery lesions) substudy. Circulation. 2004;109:2273-8.
14. Lemos PA, Arampatzis CA, Saia F, Hoye A, Degertekin M, Tanabe K et al. Treatment of very small vessels with 2.25-mm diameter sirolimus-eluting stents (from the RESEARCH registry). Am J Cardiol. 2004;93:633-6.
15. Sousa JE. SVELTE: Multicenter, Controlled Study of Sirolimus-Eluting Stents in Small Vessels. Transcatheter Cardiovascular Therapeutics (TCT), Washington, DC [presentation]. http://www.tctmd.com/csportal/appmanager/tctmd/main?_nfpb=true&_pageLabel= TCTMDContent&hdCon=814312. 2004.
16. Lemos PA, Saia F, Ligthart JM, Arampatzis CA, Sianos G, Tanabe K et al. Coronary restenosis after sirolimus-eluting stent implantation: morphological description and mechanistic analysis from a consecutive series of cases. Circulation. 2003;108:257-60.
17. Iakovou I, Mintz GS, Dangas G, Abizaid A, Mehran R, Lansky AJ et al. Optimal final lumen area and predictors of target lesion revascularization after stent implantation in small coronary arteries. Am J Cardiol. 2003;92:1171-6.
18. Sonoda S, Morino Y, Ako J, Terashima M, Hassan AH, Bonneau HN et al. Impact of final stent dimensions on long-term results following sirolimus-eluting stent implantation: serial intravascular ultrasound analysis from the sirius trial. J Am Coll Cardiol. 2004;43:1959-63.
19. Takebayashi H, Kobayashi Y, Mintz GS, Carlier SG, Fujii K, Yasuda T et al. Intravascular ultrasound assessment of lesions with target vessel failure after sirolimus-eluting stent implantation. Am J Cardiol. 2005;95:498-502.
20. Sakurai R, Ako J, Morino Y, Sonoda S, Kaneda H, Terashima M et al. Predictors of edge stenosis following sirolimus-eluting stent deployment (a quantitative intravascular ultrasound analysis from the SIRIUS trial). Am J Cardiol. 2005;96:1251-3.
Ricardo A. Costa
55 East 59th Street, 6th Floor
New York, USA, 10022
E-mail:
rcosta@crf.org
Recebido em 22/02/06
Aceito em 22/02/06
EditorialSirolimus-eluting stents for the treatment of stenoses in small coronary arteries: what have we learned?
EDITORIAL
Sirolimus-eluting stents for the treatment of stenoses in small coronary arteries: what have we learned?
Ricardo A. Costa, MD; Alexandra J. Lansky, MD
Cardiovascular Research Foundation and Columbia University Medical Center - Nova York, NY, USA
Mailing Address
Percutaneous coronary intervention (PCI) in small vessels (broadly defined as stenosis in vessel with reference diameter <2.75-2.80mm, or <3.00mm)1,2, have been historically associated with high rates of restenosis (18-52%) and vessel revascularization (up to 27%)1,3-5. Prior to drug-eluting stents (DES), a strong correlation between restenosis and vessel size was recognized, with an inverse association between vessel size and angiographic restenosis; this was attributed to the disproportionately greater amount of neointimal hyperplasia (NIH) relative to the vessel caliber in smaller vessels1,3. This phenomenon seemed to be aggravated in diabetics who often present "small" arteries because of diffuse coronary disease and exaggerated neointimal proliferative response4. Several studies had attempted to demonstrate the efficacy of stenting versus balloon angioplasty in small vessels, but results were controversial. However, a recent meta-analysis of 11 randomized trials (2,971 patients) comparing bare metal stents (BMS) versus balloon angioplasty in vessels 2.22-2.60mm, demonstrated that restenosis was improved by stent implantation (p=0.003), with relative risk of 0.77 (95% confidence interval 0.65, 0.92)1.
With the introduction of sirolimus-eluting stents (SES), many expected that the similar effectiveness of SES for preventing restenosis in uncomplicated lesions would extend to high risk subsets such as small vessels. In this issue of the Arquivos Brasileiros de Cardiologia, Devito et al6 reports the outcomes of 80 patients enrolled in a prospective, non-randomized comparison between SES (Cypher® stent) versus a BMS (ML-Pixel® stent), for the treatment of de novo coronary lesions in vessels 2.20-2.75mm in diameter. All stents were implanted successfully and final luminal dimensions were similar in both groups. (It is important to note that in this investigation, patients were consecutively enrolled at two different time points, and even though baseline clinical demographics were comparable, the two groups were not perfectly matched according to some important criteria, including lesion complexity and stent size.) At follow-up, late lumen loss (LLL), restenosis and NIH area were significantly reduced with SES; also, a 3.5-fold decrease in target lesion revascularization (TLR) was found in SES compared to BMS, a difference that did not reach statistical significance.
The performance of SES in small vessels has been evaluated in several randomized clinical trials and registries (Table 1). LLL, a surrogate of NIH, was significantly decreased with SES compared to BMS in "small vessels" by 98.7%, 78.8%, 81%, 88.2%, and 82.2% in RAVEL, SIRIUS, E-SIRIUS, C-SIRIUS, and SES-SMART, respectively2,5,7-10. In Devito's study, LLL was decreased by 77.5%, p<0.0016. A slightly higher in-stent LLL (0.36mm) was found in SIRIUS-2.25 compared to the other studies (0.01-0.21mm) (Table 1). SIRIUS-2.25 had increased rates of diabetics (40%) and complex lesions (71% B2/C) 11. Diabetics have been demonstrated to have higher LLL compared to non-diabetics12,13. In Devito's analysis, which also had 40% of diabetes but less complex lesions, LLL was 0.25mm6. Overall, these LLL were comparable to the LLL found in lesions in larger vessels treated with SES7-9,14, and were considerably lower compared to BMS (0.80-1.05mm)2,5,7,10, confirming the consistency and effectiveness of SES in preventing NIH, despite differences in diabetes rates, vessel size and lesion characteristics.
The classic inverse relationship between vessel size and restenosis was not seen with SES in RAVEL (0% restenosis in all vessel sizes)7. But, in a sub-analysis of the SIRIUS trial (which had longer and more complex lesions), lesions were divided into tertiles according to vessel size, and in-stent restenosis was 5%, 2.5%, and 1.9% with SES in small (2.32mm), "medium" (2.78mm), and large (3.31mm) vessels. Conversely, in-segment restenosis was increased in small vessels (17.6%), compared to "medium" (6.6%), and large (1.9%) vessels9. As a result, the risk reductions for in-segment restenosis with SES decreased by 93.7%, to 81.7%, to 58.8% in large, "medium", and small vessels, respectively. In SIRIUS-2.25, restenosis rates were comparable to SIRIUS "small vessel" tertile, and was associated with stent length, diabetes and number of stents implanted11. In Devito's report, there was no in-stent restenosis and only 4% in-segment restenosis with SES compared to 33.3% in-stent and 36.7% in-segment restenosis with BMS (p<0.001)6. Similar results were found in RAVEL, E- and C-SIRIUS, and SVELTE5,7,10,15. In RESEARCH, vessel size was considerably smaller compared to the other studies (Table 1), and restenosis (only in-stent) occurred mostly after treatment of ostial lesions14. Importantly, in the SES-SMART sub-analysis in diabetics, SES was associated with significant decrease in LLL and restenosis compared to BMS; however, when considering only insulin dependents (35%), restenosis with SES rose to 40%12. These data convey some considerations regarding SES in small vessels, including: 1) small vessels experience higher restenosis rates compared to larger vessels; 2) restenosis appears to increase according to lesion severity and stented length; 3) diabetics may experience higher rates of restenosis. This may be related not only to the hyperproliferative and aggressive vascular response often observed, but also to suboptimal stent deployment (incomplete lesion coverage, inadequate stent expansion, see below), since diabetics frequently present with long and diffuse disease (as mentioned before); and 4) the higher "in-segment" restenosis (compared to "in-stent") observed in the majority of studies (Table 1) may be reflecting incomplete lesion coverage and/or injured segment during PCI. This situation has been recognized8,16 and improvement in the "DES" technique – minimize peri-lesion trauma using short pre-dilatation balloons, complete lesion/injured segment coverage, short post-dilatation balloons (positioned within the stented area to prevent injury outside of the stent edges), and overlap multiple stents avoiding gaps, may be critical to optimize results in small vessels.
Previous studies with IVUS demonstrated that final luminal dimensions in vessels <2.75mm predict vessel revascularization17. Similar results were found with SES. In the IVUS sub-study of the SIRIUS trial, a final minimum stent area >4.5mm2 for vessels <2.8mm (by QCA) was found to be a threshold that predicted an "adequate" IVUS lumen at follow-up (>4.0mm2). The positive predictive value of the IVUS stent dimensions was 90%18. In addition, Takebayashi et al reported a series of patients with target vessel failure post-SES implantation where the majority of failures (especially in-stent restenosis) were associated with stent underexpansion19. This is expected as once an effective drug, (in this case, sirolimus), inhibited most of the NIH (Table 1), the main cause of in-stent restenosis became stent underexpansion. At last, a larger reference percentage of plaque area and a larger edge stent area/reference minimum lumen area were associated with edge stenosis with SES in SIRIUS20. These evidences suggest that successful SES is relied upon a combination of SES' ability to prevent NIH formation and optimal stenting technique. In the context of small vessels, IVUS guided PCI for SES implantation should be especially considered and even recommended, as it: 1) allows accurate assessment of vessel size and lesion length before the procedure, helping operators to selected the proper device and technical approach to achieve full lesion coverage and proper stented segment matching; and 2) may identify inadequate stent expansion, permitting the operator to post dilate the stent to achieve optimal stent expansion.
Finally, implantation of SES in small vessels has been associated with a high procedural success rate (>95%) and sustained safety (comparable to larger vessels treaded with SES), reflected by the low incidence of stent thrombosis and MACE during the mid- and long term follow-up (Table 1)2,5,6,8,10,11,14,15. In addition, SES led to a 70% to 81% relative reduction of TLR compared to BMS in "small vessel" randomized trials2,5,10. Importantly, both TLR and MACE rates with SES (Table 1) were remarkably low in all studies (<10%), especially given the high-risk lesions treaded and the high-risk population. These results confirm the dramatic impact and overall benefits of SES compared to BMS and historical controls of PCI in small vessels. Nevertheless, despite the impressive progress obtained in the field, small vessel is still predictive of restenosis after SES implantation8; therefore, continued efforts, including optimize DES technique and development of novel DES technologies specifically designed for small vessels, are still needed to improve outcome.
REFERENCES
1. Moreno R, Fernandez C, Alfonso F, Hernandez R, Perez-Vizcayno MJ, Escaned J et al. Coronary stenting versus balloon angioplasty in small vessels: a meta-analysis from 11 randomized studies. J Am Coll Cardiol. 2004;43:1964-72.
2. Ardissino D, Cavallini C, Bramucci E, Indolfi C, Marzocchi A, Manari A et al. Sirolimus-eluting vs uncoated stents for prevention of restenosis in small coronary arteries: a randomized trial. JAMA. 2004;292:2727-34.
3. Holmes DR Jr, Kereiakes DJ. The approach to small vessels in the era of drug-eluting stents. Rev Cardiovasc Med. 2005;6 Suppl 1:S31-7.
4. Saucedo JF, Popma JJ, Kennard ED, Talley JD, Lansky A, Leon MB et al. Relation of coronary artery size to one-year clinical events after new device angioplasty of native coronary arteries (a New Approach to Coronary Intervention [NACI] Registry Report). Am J Cardiol. 2000;85:166-71.
5. Schampaert E, Cohen EA, Schluter M, Reeves F, Traboulsi M, Title LM et al. The Canadian study of the sirolimus-eluting stent in the treatment of patients with long de novo lesions in small native coronary arteries (C-SIRIUS). J Am Coll Cardiol. 2004;43:1110-5.
6. Devito FS, Sousa AGMR, Feres F, Abizaid A, Staico R, Mattos LAP et al. Comparative Analysis of Intimal Hyperplasia After Sirolimus-Eluting Stent and Thin-Strut Bare Metal Stent Implantation in Small Coronary Arteries. Arq Bras Cardiol. 2006;86:268-75.
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