Catheterization and Cardiovascular Interventions 84:1087–1088 (2014)
Editorial Comment DES: Timing May Be Everything George W. Vetrovec* MD, MSCAI, MACC VCU Pauley Heart Center, Virginia Commonwealth University Medical Center, Richmond, Virginia
There is significant evidence that the multiple factors play a role in the safety and efficacy of drug eluting stents (DES). The success seen with DES stents is attributable to the antiproliferative effects of the drug while the polymer used to adhere the drug to the stent and control the drug delivery rate has actually performed negatively regards optimal late outcomes. Factors contributing to adverse polymer risk include a local vessel inflammatory response and late polymer cracking both of which contribute to delayed or incomplete healing and thus a continued risk of stent thrombosis which exceeds that experienced with bare metal stents (BMS) for which there is rapid “healing” and thus a lower risk of stent thrombosis but a greater risk of late restenosis due to local proliferation. Both DES and BMS reduce restenosis risk by decreasing “recoil” seen after balloon angioplasty only. Lastly, stent characteristics also affect risk of restenosis. In particular strut thickness is an important component. Thinner struts reduce the risk of restenosis. Lastly, operator deployment techniques are likewise important to maximize stent apposition. Thus, assessing which drug/stent or deployment characteristics determine clinical outcome can be problematic. The article by Ohlow and coworkers [1] in this issue of CCI describes the 5-year results of the Bad Berka Yukon Choice Registry which reports the outcomes using the Yukon sirolimus eluting stent. The stent is unique in that it has no polymer, is a thin strut design, spray coated in the cath lab with a 2% ethanolic solution of sirolimus. The registry included “real world” experience with both on and off label utilization. Overall late target vessel revascularization (TVR) was high at 24.6%, with the one year risk of stent thrombosis being 1.14% while late (>1 year) was 0.29%. Off label indications showed a 40.8% major adverse cardiac events (MACE) rate compared to 14.8% for on label indications, which is not surprising given the higher risk patients in the off label C 2014 Wiley Periodicals, Inc. V
group. The authors point out that the late rates of restenosis are higher than some prior results for the Cypher sirolimus stent. One major concern is the lack of information regards the time course and rate of sirolimus release from a nonpolymer stent, “operator prepared” in lab with a sirolimus solution. Sirolimus is a drug with high tissue binding and late tissue rerelease [2]. However, it is unclear if the coating method or the characteristics of drug release are adequate to derive effective local tissue drug effect for a sufficient time given the lack of a polymer and no described quality control for the actual coating process. An earlier trial using paclitaxel showed a lack of efficacy for paclitaxel adhered directly to a BMS whereas paclitaxel delivered via a polymer with much slower and continuous release characteristics was repeatedly shown to be effective. Thus, data from the current study seem to reflect TVR outcomes which might be expected from a thin strut, BMS which raises the question as to how effective the sirolimus was to the stent outcomes given the potential for inconsistent drug loading and rapid but short release of the sirolimus. This registry inadvertently seems to support the concept that stent drug delivery characteristics are important. Thus, as we move to the “perfect” vascular repair device, multiple factors have to be considered including adequate hoop strength to effectively prevent recoil, an effective antiproliferative agent delivered at a rate and over an appropriate time course to limit proliferation to an extent which prevents functionally important (ischemia producing)
Conflict of interest: Nothing to report. *Correspondence to: George W. Vetrovec, MD, MSCAI, MACC; VCU Pauley Heart Center, Virginia Commonwealth University Medical Center, Richmond, VA. E-mail: [email protected] Received 9 October 2014; Revision accepted 10 October 2014 DOI: 10.1002/ccd.25697 Published online 19 November 2014 in Wiley Online Library (wileyonlinelibrary.com)
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restenosis without producing unnecessarily severe delayed healing of the artery which contributes to the early risk of stent thrombosis. It is likely to achieve the optimal device there will need to be a polymer to “hold” the antiproliferative drug either on a metal stent or within a polymer bioabsorbable stent and control drug release rate. As a part of this the timing of drug release remains an important component.
REFERENCES 1. Ohlow MA, von Korn H, Gunkel O, Farah A, Fuhrmann JT, Lauer B. Incidence of adverse cardiac events 5 years after polymer-free sirolimus eluting stent implantation: Results from the prospective Bad Berka Yukon Choice registry. Catheter Cardiovasc Interv. 2013;84:1080–1086. 2. Vetrovec GW, Rizik D, Willard C, et al. Sirolimus PK Trial: A pharmacokinetic study of sirolimus-eluting Bx velocity stent in patients with De Novo coronary lesions. Catheter Cardiovasc Interv 2006;67:32–37.
Catheterization and Cardiovascular Interventions DOI 10.1002/ccd. Published on behalf of The Society for Cardiovascular Angiography and Interventions (SCAI).
Editorial Comment DES: Timing May Be Everything George W. Vetrovec* MD, MSCAI, MACC VCU Pauley Heart Center, Virginia Commonwealth University Medical Center, Richmond, Virginia
There is significant evidence that the multiple factors play a role in the safety and efficacy of drug eluting stents (DES). The success seen with DES stents is attributable to the antiproliferative effects of the drug while the polymer used to adhere the drug to the stent and control the drug delivery rate has actually performed negatively regards optimal late outcomes. Factors contributing to adverse polymer risk include a local vessel inflammatory response and late polymer cracking both of which contribute to delayed or incomplete healing and thus a continued risk of stent thrombosis which exceeds that experienced with bare metal stents (BMS) for which there is rapid “healing” and thus a lower risk of stent thrombosis but a greater risk of late restenosis due to local proliferation. Both DES and BMS reduce restenosis risk by decreasing “recoil” seen after balloon angioplasty only. Lastly, stent characteristics also affect risk of restenosis. In particular strut thickness is an important component. Thinner struts reduce the risk of restenosis. Lastly, operator deployment techniques are likewise important to maximize stent apposition. Thus, assessing which drug/stent or deployment characteristics determine clinical outcome can be problematic. The article by Ohlow and coworkers [1] in this issue of CCI describes the 5-year results of the Bad Berka Yukon Choice Registry which reports the outcomes using the Yukon sirolimus eluting stent. The stent is unique in that it has no polymer, is a thin strut design, spray coated in the cath lab with a 2% ethanolic solution of sirolimus. The registry included “real world” experience with both on and off label utilization. Overall late target vessel revascularization (TVR) was high at 24.6%, with the one year risk of stent thrombosis being 1.14% while late (>1 year) was 0.29%. Off label indications showed a 40.8% major adverse cardiac events (MACE) rate compared to 14.8% for on label indications, which is not surprising given the higher risk patients in the off label C 2014 Wiley Periodicals, Inc. V
group. The authors point out that the late rates of restenosis are higher than some prior results for the Cypher sirolimus stent. One major concern is the lack of information regards the time course and rate of sirolimus release from a nonpolymer stent, “operator prepared” in lab with a sirolimus solution. Sirolimus is a drug with high tissue binding and late tissue rerelease [2]. However, it is unclear if the coating method or the characteristics of drug release are adequate to derive effective local tissue drug effect for a sufficient time given the lack of a polymer and no described quality control for the actual coating process. An earlier trial using paclitaxel showed a lack of efficacy for paclitaxel adhered directly to a BMS whereas paclitaxel delivered via a polymer with much slower and continuous release characteristics was repeatedly shown to be effective. Thus, data from the current study seem to reflect TVR outcomes which might be expected from a thin strut, BMS which raises the question as to how effective the sirolimus was to the stent outcomes given the potential for inconsistent drug loading and rapid but short release of the sirolimus. This registry inadvertently seems to support the concept that stent drug delivery characteristics are important. Thus, as we move to the “perfect” vascular repair device, multiple factors have to be considered including adequate hoop strength to effectively prevent recoil, an effective antiproliferative agent delivered at a rate and over an appropriate time course to limit proliferation to an extent which prevents functionally important (ischemia producing)
Conflict of interest: Nothing to report. *Correspondence to: George W. Vetrovec, MD, MSCAI, MACC; VCU Pauley Heart Center, Virginia Commonwealth University Medical Center, Richmond, VA. E-mail: [email protected] Received 9 October 2014; Revision accepted 10 October 2014 DOI: 10.1002/ccd.25697 Published online 19 November 2014 in Wiley Online Library (wileyonlinelibrary.com)
1088
Vetrovec
restenosis without producing unnecessarily severe delayed healing of the artery which contributes to the early risk of stent thrombosis. It is likely to achieve the optimal device there will need to be a polymer to “hold” the antiproliferative drug either on a metal stent or within a polymer bioabsorbable stent and control drug release rate. As a part of this the timing of drug release remains an important component.
REFERENCES 1. Ohlow MA, von Korn H, Gunkel O, Farah A, Fuhrmann JT, Lauer B. Incidence of adverse cardiac events 5 years after polymer-free sirolimus eluting stent implantation: Results from the prospective Bad Berka Yukon Choice registry. Catheter Cardiovasc Interv. 2013;84:1080–1086. 2. Vetrovec GW, Rizik D, Willard C, et al. Sirolimus PK Trial: A pharmacokinetic study of sirolimus-eluting Bx velocity stent in patients with De Novo coronary lesions. Catheter Cardiovasc Interv 2006;67:32–37.
Catheterization and Cardiovascular Interventions DOI 10.1002/ccd. Published on behalf of The Society for Cardiovascular Angiography and Interventions (SCAI).
