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Direct comparison of the short-term clinical performance of Z Guidant and Taxus stents
International Journal of Cardiology 145 (2010) e83 – e85 www.elsevier.com/locate/ijcard
Letter to the Editor
Direct comparison of the short-term clinical performance of Z Guidant and Taxus stents Anna Guildford a , Paola Colombo b , Giuseppe Bruschi b , Edgardo Bonacina b , Silvio Klugmann b , Matteo Santin a,⁎ a
School of Pharmacy and Biomolecular Sciences, University of Brighton, UK b Niguarda Hospital, Milan, Italy Received 9 October 2008; accepted 14 December 2008
Abstract The recent introduction of drug-eluting stents in angioplasty of atherosclerotic blood vessels has significantly reduced the risks of in-stent restenosis (ISR) [1]. Indeed, it is known that in conventional stents ISR takes place in over 20% of the cases and up to 60% when implanted in diabetic patients. Conversely, clinical trials have shown that drug-eluting stents have significantly reduced ISR. Among the drug-eluting stents available on the market, Taxus stents (Tax, Boston Scientific, USA) are among the most used devices ,[2]. Tax are stainless-steel stents coated with Translute, a poly(styrene-b-isobutylene-b-styrene) polymer (PSIBS) eluting Placlitaxel, an anti-mitotic drug. Clinical trials on this type of drug-eluting stents have shown an incidence of restenosis of approximately 4%. The majority of these trials were randomized studies where conventional stents and drug-eluting devices have been implanted in separate patients' cohorts. Such a randomized design, although fundamental to collect statistically-relevant data, does not allow a direct histological comparison of different stent types when implanted in the same patient and do not show the individual susceptibility to the host response especially at short-term implantation times. Here, an interesting case study is presented where two chrome-cobalt stents (Z Guidant, ZG, Guidant Corp.) and a Tax have been simultaneously implanted in the same patient in three separate coronary arteries, retrieved after only 8 weeks and histologically analysed. © 2009 Elsevier Ireland Ltd. All rights reserved. Keywords: Cardiovascular stents; In-stent restenosis; Drug-eluting stents; Bare metal stents; Hyaluronan; Neointima
1. Case review This article illustrates a direct histological comparison between a medicated (Taxus) and 2 non-medicated (Z Guidant) stents which were implanted in a 75-year old male patient, admitted to the intensive cardiac care unit of Niguarda Hospital, Milan, Italy in March 2005 with unstable angina. The patient was a previous smoker, with hypertension and hyperlipidemia, with no history of diabetes. The patient had severe renal failure and had been undergoing dialysis therapy since July 2003. A severe peripheral ⁎ Corresponding author. School of Pharmacy and Biomolecular Sciences, University of Brighton, Cockcroft Building Lewes Road, Brighton BN2 4GJ, UK. Tel.: +44 0 1273 642083; fax: +44 0 1273 679333. E-mail address: [email protected] (M. Santin). 0167-5273/$ - see front matter © 2009 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.ijcard.2008.12.161
polyvasculopathy was diagnosed and the patient underwent both an abdominal aortic aneurismectomy and a right carotid thrombo-endoarterectomy. Coronary angiogram performed with a left radial approach, showed: (i) a N20 mm–long 80% diameter stenosis extended from the proximal to midsegment of the left anterior descending coronary artery (LAD), (ii) a N 20 mm–long 90% diameter stenosis in the mid of the left circumflex coronary artery (LCx), (iii) a 80% diameter stenosis in the mid of the right coronary artery (RCA). The LAD lesion was pre-dilated with an undersized balloon (2.5/20 mm at 8 atm) and a drug-eluting Taxus (TAX) stent (2.75/24 mm) was implanted by being postdilated with a 3.0 balloon at 14 atm. The LCx artery lesion was pre-dilated with an undersized balloon (3.0/15 mm at 14 atm) followed by Zeta Guidant (ZG) non-medicated stent implantation (3.5/23 mm at14 atm). The RCA lesion was
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A. Guildford et al. / International Journal of Cardiology 145 (2010) e83–e85
pre-dilated with an undersized balloon (2.5/20 mm at 8 atm) and followed by deployment of ZG stent (2.75/13 mm at 14 atm). The patient remained asymptomatic for 15 days before experiencing symptoms of pulmonary oedema with-
out angina, this led to his re-hospitalisation and to an emergency coronary angiography which showed the patency of all implanted stents (Fig. 1a and b). During hospitalisation the patient developed a pulmonary infection and sepsis
Fig. 1. Comparative assessment of coronary arteries implanted with ZG and TAX stents. Angiographies of coronary arteries at the time of patience rehospitalisation show pervious vessels (a and b). Typical histological features of pervious ZG implanted in LCx and RCA (c and d). Typical histological features of restenotic ZG implanted in LCx and RCA (e and f). Typical histological features of TAX-implanted LAD (g and h). Arrow in h shows gap between the metal strut and the tissue with morphological features different from tearing.
A. Guildford et al. / International Journal of Cardiology 145 (2010) e83–e85
which was microbiologically assessed as Pseudomonas aeruginosa-positive. The patient died in May 2005, 8 weeks after stent implantation. Autopsy showed chronic adhesive pericarditis with intrapericardial organized haematoma. Following the patient's death, the vessels were retrieved and histomorphometrically analysed using Safranin O staining. In the case of ZGs, as previously reported by other authors [1], orange staining highlighted the prevalence of a hyaluronan-rich extracellular matrix both around the primary plaque and the restenotic tissue (Fig. 1c–f). Sequential sectioning showed that the ZG struts were predominantly surrounded by neointimal tissue in both LCx (83.8 ± 5.6%) and RCA (96.7 ± 3.3%) despite the absence (Fig. 1c and d) or presence (Fig. 1e and f) of significant in-stent restenosis. Tissue tearing was observed and was attributed to artifacts caused during specimen preparation. Conversely, the TAX device showed a significantly limited expansion resulting in a constant, ellipsoid cross-section and no stent strut penetration into the atherosclerotic tissue (Fig. 1g), only 35.5 ± 9.2% of the TAX struts were found encapsulated in newly formed neointima; the percentage being significant different from ZG struts at p b 0.05 [ANOVA (Tukey's test)]. Over 82% of the stent struts of the TAX device showed gaps different from tissue tearing between the tissue and the stent strut indicating possible polymer coating delamination (Fig. 1h). In summary the TAX stent offered mechanical pliability which resulted in a reduced but constant vessel patency with no clinically relevant ISR. In contrast the ZG device showed areas of vessel wall penetration associated with ISR and
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areas of complete focal restriction. It is suggested that penetration of the foreign material into the highly-inflamed atherosclerotic tissue may exacerbated host response and neointimal formation through the deposition of a hyaluronan-rich extracellular matrix resembling an incomplete healing response [3]. Conversely, the clinical performance of the TAX stent may be explained not only by the elution of drug, but also by the pliability of the device that minimizes penetration into the atherosclerotic vessel wall. In this type of stent, the drug eluting polymer does not inhibit cell colonization and a possible delamination may lead to poor integration of the struts into the neointima. Acknowledgements The authors of this manuscript have certified that they comply with the Principles of Ethical Publishing in the Journal of Cardiology [4]. References [1] Santin M, Colombo P, Bruschi G. Interfacial biology of in stent restenosis. Exp Rev Med Dev 2005;2:429–43. [2] Rogers C. Paclitaxel release from inert polymer material-coated stents curtails coronary in-stent restenosis in pigs. Circulation 2000;102(Suppl 18):11566–7. [3] Farb A, Weber DK, Kolodgie FD, Burke AP, Virmani R. Morphological predictors of restenosis after coronary stenting in humans. Circulation 2002;105:2974–80. [4] Coats AJ. Ethical authorship and publishing. Int J Cardiol 2009;131: 149–50.
Letter to the Editor
Direct comparison of the short-term clinical performance of Z Guidant and Taxus stents Anna Guildford a , Paola Colombo b , Giuseppe Bruschi b , Edgardo Bonacina b , Silvio Klugmann b , Matteo Santin a,⁎ a
School of Pharmacy and Biomolecular Sciences, University of Brighton, UK b Niguarda Hospital, Milan, Italy Received 9 October 2008; accepted 14 December 2008
Abstract The recent introduction of drug-eluting stents in angioplasty of atherosclerotic blood vessels has significantly reduced the risks of in-stent restenosis (ISR) [1]. Indeed, it is known that in conventional stents ISR takes place in over 20% of the cases and up to 60% when implanted in diabetic patients. Conversely, clinical trials have shown that drug-eluting stents have significantly reduced ISR. Among the drug-eluting stents available on the market, Taxus stents (Tax, Boston Scientific, USA) are among the most used devices ,[2]. Tax are stainless-steel stents coated with Translute, a poly(styrene-b-isobutylene-b-styrene) polymer (PSIBS) eluting Placlitaxel, an anti-mitotic drug. Clinical trials on this type of drug-eluting stents have shown an incidence of restenosis of approximately 4%. The majority of these trials were randomized studies where conventional stents and drug-eluting devices have been implanted in separate patients' cohorts. Such a randomized design, although fundamental to collect statistically-relevant data, does not allow a direct histological comparison of different stent types when implanted in the same patient and do not show the individual susceptibility to the host response especially at short-term implantation times. Here, an interesting case study is presented where two chrome-cobalt stents (Z Guidant, ZG, Guidant Corp.) and a Tax have been simultaneously implanted in the same patient in three separate coronary arteries, retrieved after only 8 weeks and histologically analysed. © 2009 Elsevier Ireland Ltd. All rights reserved. Keywords: Cardiovascular stents; In-stent restenosis; Drug-eluting stents; Bare metal stents; Hyaluronan; Neointima
1. Case review This article illustrates a direct histological comparison between a medicated (Taxus) and 2 non-medicated (Z Guidant) stents which were implanted in a 75-year old male patient, admitted to the intensive cardiac care unit of Niguarda Hospital, Milan, Italy in March 2005 with unstable angina. The patient was a previous smoker, with hypertension and hyperlipidemia, with no history of diabetes. The patient had severe renal failure and had been undergoing dialysis therapy since July 2003. A severe peripheral ⁎ Corresponding author. School of Pharmacy and Biomolecular Sciences, University of Brighton, Cockcroft Building Lewes Road, Brighton BN2 4GJ, UK. Tel.: +44 0 1273 642083; fax: +44 0 1273 679333. E-mail address: [email protected] (M. Santin). 0167-5273/$ - see front matter © 2009 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.ijcard.2008.12.161
polyvasculopathy was diagnosed and the patient underwent both an abdominal aortic aneurismectomy and a right carotid thrombo-endoarterectomy. Coronary angiogram performed with a left radial approach, showed: (i) a N20 mm–long 80% diameter stenosis extended from the proximal to midsegment of the left anterior descending coronary artery (LAD), (ii) a N 20 mm–long 90% diameter stenosis in the mid of the left circumflex coronary artery (LCx), (iii) a 80% diameter stenosis in the mid of the right coronary artery (RCA). The LAD lesion was pre-dilated with an undersized balloon (2.5/20 mm at 8 atm) and a drug-eluting Taxus (TAX) stent (2.75/24 mm) was implanted by being postdilated with a 3.0 balloon at 14 atm. The LCx artery lesion was pre-dilated with an undersized balloon (3.0/15 mm at 14 atm) followed by Zeta Guidant (ZG) non-medicated stent implantation (3.5/23 mm at14 atm). The RCA lesion was
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A. Guildford et al. / International Journal of Cardiology 145 (2010) e83–e85
pre-dilated with an undersized balloon (2.5/20 mm at 8 atm) and followed by deployment of ZG stent (2.75/13 mm at 14 atm). The patient remained asymptomatic for 15 days before experiencing symptoms of pulmonary oedema with-
out angina, this led to his re-hospitalisation and to an emergency coronary angiography which showed the patency of all implanted stents (Fig. 1a and b). During hospitalisation the patient developed a pulmonary infection and sepsis
Fig. 1. Comparative assessment of coronary arteries implanted with ZG and TAX stents. Angiographies of coronary arteries at the time of patience rehospitalisation show pervious vessels (a and b). Typical histological features of pervious ZG implanted in LCx and RCA (c and d). Typical histological features of restenotic ZG implanted in LCx and RCA (e and f). Typical histological features of TAX-implanted LAD (g and h). Arrow in h shows gap between the metal strut and the tissue with morphological features different from tearing.
A. Guildford et al. / International Journal of Cardiology 145 (2010) e83–e85
which was microbiologically assessed as Pseudomonas aeruginosa-positive. The patient died in May 2005, 8 weeks after stent implantation. Autopsy showed chronic adhesive pericarditis with intrapericardial organized haematoma. Following the patient's death, the vessels were retrieved and histomorphometrically analysed using Safranin O staining. In the case of ZGs, as previously reported by other authors [1], orange staining highlighted the prevalence of a hyaluronan-rich extracellular matrix both around the primary plaque and the restenotic tissue (Fig. 1c–f). Sequential sectioning showed that the ZG struts were predominantly surrounded by neointimal tissue in both LCx (83.8 ± 5.6%) and RCA (96.7 ± 3.3%) despite the absence (Fig. 1c and d) or presence (Fig. 1e and f) of significant in-stent restenosis. Tissue tearing was observed and was attributed to artifacts caused during specimen preparation. Conversely, the TAX device showed a significantly limited expansion resulting in a constant, ellipsoid cross-section and no stent strut penetration into the atherosclerotic tissue (Fig. 1g), only 35.5 ± 9.2% of the TAX struts were found encapsulated in newly formed neointima; the percentage being significant different from ZG struts at p b 0.05 [ANOVA (Tukey's test)]. Over 82% of the stent struts of the TAX device showed gaps different from tissue tearing between the tissue and the stent strut indicating possible polymer coating delamination (Fig. 1h). In summary the TAX stent offered mechanical pliability which resulted in a reduced but constant vessel patency with no clinically relevant ISR. In contrast the ZG device showed areas of vessel wall penetration associated with ISR and
e85
areas of complete focal restriction. It is suggested that penetration of the foreign material into the highly-inflamed atherosclerotic tissue may exacerbated host response and neointimal formation through the deposition of a hyaluronan-rich extracellular matrix resembling an incomplete healing response [3]. Conversely, the clinical performance of the TAX stent may be explained not only by the elution of drug, but also by the pliability of the device that minimizes penetration into the atherosclerotic vessel wall. In this type of stent, the drug eluting polymer does not inhibit cell colonization and a possible delamination may lead to poor integration of the struts into the neointima. Acknowledgements The authors of this manuscript have certified that they comply with the Principles of Ethical Publishing in the Journal of Cardiology [4]. References [1] Santin M, Colombo P, Bruschi G. Interfacial biology of in stent restenosis. Exp Rev Med Dev 2005;2:429–43. [2] Rogers C. Paclitaxel release from inert polymer material-coated stents curtails coronary in-stent restenosis in pigs. Circulation 2000;102(Suppl 18):11566–7. [3] Farb A, Weber DK, Kolodgie FD, Burke AP, Virmani R. Morphological predictors of restenosis after coronary stenting in humans. Circulation 2002;105:2974–80. [4] Coats AJ. Ethical authorship and publishing. Int J Cardiol 2009;131: 149–50.