Bioabsorbable stents: Difference between revisions
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* Lack of toxicity | * Lack of toxicity | ||
Polymers have been widely used in Cardiovascular devices and are now primarily used as delivery vehicles for drug coatings. | Polymers have been widely used in Cardiovascular devices and are now primarily used as delivery vehicles for drug coatings. Polymers suggested for bioabsorbable stents are Poly-L-Lactic acid(PLLA), polyglycolic acid(PGA),Poly(D,L-lactide/glycolide) copolymer(PDLA) and polycaprolactone. The use of bioabsorbable polymer coating reduces the need for extended dual anti-platelet therapy and in turn late thrombotic events. Among the polymers, Poly-L-Lactic acid is widely used in medicine. It breaks down to lactic acid a natural metabolite in human body, which enters [[Krebs Cycle]] and is metabolized to [[carbon dioxide]] and water. <ref> http://www.medscape.com/viewarticle/523241_2</ref> | ||
So far two bioabsorbable metals alloys have been proposed for this application: [[magnesium]] and iron.The factors that determine the biocompatibility of these alloys are their solubility and their released degradation products. Magnesium stents are made of 93% magnesium and 7% rare-earth-metals. Magnesium is chosen because it is an essential element in the body. The alloy induces rapid endothelialization, has low thrombogenicity and has a degradation time of 2-3 months. It has calcium antagonist and antiarrhythmic properties and is also not associated with any adverse reactions.<ref>http://onlinelibrary.wiley.com/doi/10.1002/ccd.20727/abstract;jsessionid=8D3133482E4FE43C7025F17E0655A06F.d03t01?userIsAuthenticated=false&deniedAccessCustomisedMessage=</ref> | So far two bioabsorbable metals alloys have been proposed for this application: [[magnesium]] and iron.The factors that determine the biocompatibility of these alloys are their solubility and their released degradation products. Magnesium stents are made of 93% magnesium and 7% rare-earth-metals. Magnesium is chosen because it is an essential element in the body. The alloy induces rapid endothelialization, has low thrombogenicity and has a degradation time of 2-3 months. It has calcium antagonist and antiarrhythmic properties and is also not associated with any adverse reactions.<ref>http://onlinelibrary.wiley.com/doi/10.1002/ccd.20727/abstract;jsessionid=8D3133482E4FE43C7025F17E0655A06F.d03t01?userIsAuthenticated=false&deniedAccessCustomisedMessage=</ref> | ||
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* Bioabsorbable therapeutics and REVA medical are testing stents coated with [[sirolimus]] and [[paclitaxel]] respectively.<ref name="pmid12050336">{{cite journal |author=Morice MC, Serruys PW, Sousa JE, ''et al.'' |title=A randomized comparison of a sirolimus-eluting stent with a standard stent for coronary revascularization |journal=N. Engl. J. Med. |volume=346 |issue=23 |pages=1773–80|year=2002 |month=June |pmid=12050336 |doi=10.1056/NEJMoa012843 |url=}}</ref> | * Bioabsorbable therapeutics and REVA medical are testing stents coated with [[sirolimus]] and [[paclitaxel]] respectively.<ref name="pmid12050336">{{cite journal |author=Morice MC, Serruys PW, Sousa JE, ''et al.'' |title=A randomized comparison of a sirolimus-eluting stent with a standard stent for coronary revascularization |journal=N. Engl. J. Med. |volume=346 |issue=23 |pages=1773–80|year=2002 |month=June |pmid=12050336 |doi=10.1056/NEJMoa012843 |url=}}</ref> | ||
* The '''PROGRESS-AMS study''' is a prospective multicenter non-randomized study that used the Magnesium-alloy stent and was conducted on 63 patients. The results of this study are 100% device and procedural success rate and the study met it's primary endpoint of MACE(major adverse cardiac events) of <30%. The immediate angiographic results were similar to those after deployment of other metallic stents. Although the stent was absorbed completely within 2 months radial support was lost much earlier so that there was an insufficient radial strength to counter negative remodeling forces after [[PCI]]. Consequently there was high restenosis rate at 4 months of almost 50% and target vessel revascularization at 1 year was 45%. There were no deaths, MIs or stent thromboses, and the stent was no longer detectable by [[IVUS]]. The high restenosis rate may raise concern about safety.<ref name="pmid17544767">{{cite journal |author=Erbel R, Di Mario C, Bartunek J, ''et al.'' |title=Temporary scaffolding of coronary arteries with bioabsorbable magnesium stents: a prospective, non-randomised multicentre trial |journal=Lancet |volume=369 |issue=9576 |pages=1869–75 |year=2007 |month=June |pmid=17544767 |doi=10.1016/S0140-6736(07)60853-8 |url=}}</ref> | * The '''PROGRESS-AMS study''' is a prospective multicenter non-randomized study that used the Magnesium-alloy stent and was conducted on 63 patients. The results of this study are 100% device and procedural success rate and the study met it's primary endpoint of MACE(major adverse cardiac events) of <30%. The immediate angiographic results were similar to those after deployment of other metallic stents. Although the stent was absorbed completely within 2 months radial support was lost much earlier so that there was an insufficient radial strength to counter negative remodeling forces after [[PCI]]. Consequently there was high restenosis rate at 4 months of almost 50% and target vessel revascularization at 1 year was 45%. There were no deaths, MIs or stent thromboses, and the stent was no longer detectable by [[IVUS]]. The high restenosis rate may raise concern about safety.<ref name="pmid17544767">{{cite journal |author=Erbel R, Di Mario C, Bartunek J, ''et al.'' |title=Temporary scaffolding of coronary arteries with bioabsorbable magnesium stents: a prospective, non-randomised multicentre trial |journal=Lancet |volume=369 |issue=9576 |pages=1869–75 |year=2007 |month=June |pmid=17544767 |doi=10.1016/S0140-6736(07)60853-8 |url=}}</ref> | ||
* The '''ABSORB trial''' involving Abbott's drug eluting BVS stent is a prospective non-randomized two phase study on 131 patients. | * The '''ABSORB trial''' involving Abbott's drug eluting BVS stent is a prospective non-randomized two phase study on 131 patients. Key endpoints include assessments of safety - major adverse cardiovascular events(MACE) and treated-site thrombosis rates - at 30 days and 6,9,12,24 months with additional annual clinical follow up for up to 5 years. The first phase (cohort A) of the trial enrolled 30 patients and its 2 year results demonstrated the following key features: | ||
** A 0% rate of stent thrombosis for all patients | |||
** No new MACE between 6 months and 2 years. At 2 years the device demonstrated a MACE rate of 3.6% (1 patient) | |||
** Bioabsorption of the stent at 2 years after implantation as confirmed by an assessment of the stent struts using optical coherence tomography[[OCT]] | |||
** Restoration of vasomotion (ability of the blood vessel to contract and expand) | |||
** Reduction in plaque area in treated arteries as confirmed by [[IVUS]] and virtual histology. | |||
The second phase (cohort B) of the trial enrolled 101 patients and incorporates device enhancements designed to improve deliverability and vessel support. 30 day results demonstrated no cases of blood clots, no need for repeat procedures and a very low rate of MACE. At 1 year the MACE was 6.9% and no reports of thrombosis. <ref name="pmid18342684">{{cite journal |author=Ormiston JA, Serruys PW, Regar E, ''et al.'' |title=A bioabsorbable everolimus-eluting coronary stent system for patients with single de-novo coronary artery lesions (ABSORB): a prospective open-label trial |journal=Lancet |volume=371 |issue=9616 |pages=899–907 |year=2008 |month=March |pmid=18342684 |doi=10.1016/S0140-6736(08)60415-8 |url=}}</ref> <ref name="pmid19286089">{{cite journal |author=Serruys PW, Ormiston JA, Onuma Y, ''et al.'' |title=A bioabsorbable everolimus-eluting coronary stent system (ABSORB): 2-year outcomes and results from multiple imaging methods |journal=Lancet |volume=373 |issue=9667 |pages=897–910 |year=2009 |month=March |pmid=19286089 |doi=10.1016/S0140-6736(09)60325-1 |url=}}</ref> | |||
* In the '''EVOLVE trial''' experts compared 2 bioabsorbable polymer SYNERGY stents - one deliverig full dose of [[everolimus]] and one delivering half dose of the drug with the durable PROMUS ELEMENT metal stent delivering full dose of the drug in 291 patients. The angiographic outcomes of the study suggest that it may be possible to achieve at least comparable efficacy with a lower dose of everolimus than is used in commercialy available everolimus-eluting stents.<ref> Meredith I, et al "Primary endpoint results of the EVOLVE trial: a randomized evaluation of a novel bioabsorbable polymer-coated, everolimus-eluting coronary stent" J Am Coll Cardiol 2012; DOI: | * In the '''EVOLVE trial''' experts compared 2 bioabsorbable polymer SYNERGY stents - one deliverig full dose of [[everolimus]] and one delivering half dose of the drug with the durable PROMUS ELEMENT metal stent delivering full dose of the drug in 291 patients. The angiographic outcomes of the study suggest that it may be possible to achieve at least comparable efficacy with a lower dose of everolimus than is used in commercialy available everolimus-eluting stents.<ref> Meredith I, et al "Primary endpoint results of the EVOLVE trial: a randomized evaluation of a novel bioabsorbable polymer-coated, everolimus-eluting coronary stent" J Am Coll Cardiol 2012; DOI: | ||
10.1016/j.jacc.2011.12.016 </ref> <ref name="pmid22341736">{{cite journal |author=Meredith IT, Verheye S, Dubois CL, ''et al.'' |title=Primary Endpoint Results of the EVOLVE Trial: A Randomized Evaluation of a Novel Bioabsorbable Polymer-Coated, Everolimus-Eluting Coronary Stent |journal=J. Am. Coll. Cardiol.|volume=59 |issue=15 |pages=1362–70 |year=2012 |month=April |pmid=22341736 |doi=10.1016/j.jacc.2011.12.016 |url=}}</ref> | 10.1016/j.jacc.2011.12.016 </ref> <ref name="pmid22341736">{{cite journal |author=Meredith IT, Verheye S, Dubois CL, ''et al.'' |title=Primary Endpoint Results of the EVOLVE Trial: A Randomized Evaluation of a Novel Bioabsorbable Polymer-Coated, Everolimus-Eluting Coronary Stent |journal=J. Am. Coll. Cardiol.|volume=59 |issue=15 |pages=1362–70 |year=2012 |month=April |pmid=22341736 |doi=10.1016/j.jacc.2011.12.016 |url=}}</ref> | ||
Revision as of 16:16, 21 May 2012
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1], Associate Editor(s)-In-Chief Raviteja Reddy Guddeti, M.B.B.S.
Overview
Bioabsorbable stents also known as the disappearing stents are a promising new discovery in the field of Interventional Cardiology.They have been an interesting field of research over the past decade and half. As the name suggests they get absorbed completely over a period of time after their work is done. Percutaneous Coronary Intervention (PCI) with bioabsorbable stents has created interest because the need for mechanical support for the healing artery is temporary, and beyond the first few months the presence of a bare metallic prosthesis has potential disadvantages.[1] [2]
Types
Bioabsorbable stents can be broadly classified into two types - Polymeric and metallic types. The key features to be considered while selecting a polymer or an alloy for a bioabsorbable stent are:
- Strength - to avoid potential immediate recoil
- Rate of degradation and corrosion
- Biocompatibility with the vessel wall
- Lack of toxicity
Polymers have been widely used in Cardiovascular devices and are now primarily used as delivery vehicles for drug coatings. Polymers suggested for bioabsorbable stents are Poly-L-Lactic acid(PLLA), polyglycolic acid(PGA),Poly(D,L-lactide/glycolide) copolymer(PDLA) and polycaprolactone. The use of bioabsorbable polymer coating reduces the need for extended dual anti-platelet therapy and in turn late thrombotic events. Among the polymers, Poly-L-Lactic acid is widely used in medicine. It breaks down to lactic acid a natural metabolite in human body, which enters Krebs Cycle and is metabolized to carbon dioxide and water. [3]
So far two bioabsorbable metals alloys have been proposed for this application: magnesium and iron.The factors that determine the biocompatibility of these alloys are their solubility and their released degradation products. Magnesium stents are made of 93% magnesium and 7% rare-earth-metals. Magnesium is chosen because it is an essential element in the body. The alloy induces rapid endothelialization, has low thrombogenicity and has a degradation time of 2-3 months. It has calcium antagonist and antiarrhythmic properties and is also not associated with any adverse reactions.[4]
The following is the list of some of the bioabsorbable stents that are currently under trials.
| Stent | Strut Material | Coating material | Design | Absorption products | Drug |
| Igaki-Tamai | Poly-L-Lactic acid | Nil | Zig-Zag helical coils with straight bridges | Lactic acid,CO2 and H2O | Nil |
| REVA | Poly(DTE carbonate) with Iodine on the backbone | Nil | Slide and lock design | Amino acids,ethanol,CO2 | paclitaxel |
| Biotronic Mg-Alloy stent | Magnesium-alloy | Nil | Sinusoidal in-phase hoops linked by straight bridges | Not applicable | Nil |
| Abbott's BVS stent | Poly-L-Lactic acid | Poly-D,L-lactide | out of phase sinusoidal hoops with straight and direct links in cohort-A & in-phase hoops with straight links in cohort-B | lactic acid, CO2,H2O | Everolimus |
| Bioabsorbable therapeutics | polymer salicylate + linker | Salicylate + different linker | tube with laser cut voids | salicylate,CO2,H2O | sirolimus |
Supportive trial data
- The Igaki-Tamai stent was one of the first bioabsorbable stents to be tested in clinical trials.In the preliminary in-man prospective non-randomized clinical trials that involved 50 patients, a 4 year follow up of all patients revealed a low complication rate with 1 in-hospital stent thrombosis causing Q-wave Myocardial Infarction, 1 non-cardiac death, 18% repeat PCI and no surgical revascularization. This stent is no longer in development now.
- Bioabsorbable therapeutics and REVA medical are testing stents coated with sirolimus and paclitaxel respectively.[6]
- The PROGRESS-AMS study is a prospective multicenter non-randomized study that used the Magnesium-alloy stent and was conducted on 63 patients. The results of this study are 100% device and procedural success rate and the study met it's primary endpoint of MACE(major adverse cardiac events) of <30%. The immediate angiographic results were similar to those after deployment of other metallic stents. Although the stent was absorbed completely within 2 months radial support was lost much earlier so that there was an insufficient radial strength to counter negative remodeling forces after PCI. Consequently there was high restenosis rate at 4 months of almost 50% and target vessel revascularization at 1 year was 45%. There were no deaths, MIs or stent thromboses, and the stent was no longer detectable by IVUS. The high restenosis rate may raise concern about safety.[7]
- The ABSORB trial involving Abbott's drug eluting BVS stent is a prospective non-randomized two phase study on 131 patients. Key endpoints include assessments of safety - major adverse cardiovascular events(MACE) and treated-site thrombosis rates - at 30 days and 6,9,12,24 months with additional annual clinical follow up for up to 5 years. The first phase (cohort A) of the trial enrolled 30 patients and its 2 year results demonstrated the following key features:
- A 0% rate of stent thrombosis for all patients
- No new MACE between 6 months and 2 years. At 2 years the device demonstrated a MACE rate of 3.6% (1 patient)
- Bioabsorption of the stent at 2 years after implantation as confirmed by an assessment of the stent struts using optical coherence tomographyOCT
- Restoration of vasomotion (ability of the blood vessel to contract and expand)
- Reduction in plaque area in treated arteries as confirmed by IVUS and virtual histology.
The second phase (cohort B) of the trial enrolled 101 patients and incorporates device enhancements designed to improve deliverability and vessel support. 30 day results demonstrated no cases of blood clots, no need for repeat procedures and a very low rate of MACE. At 1 year the MACE was 6.9% and no reports of thrombosis. [8] [9]
- In the EVOLVE trial experts compared 2 bioabsorbable polymer SYNERGY stents - one deliverig full dose of everolimus and one delivering half dose of the drug with the durable PROMUS ELEMENT metal stent delivering full dose of the drug in 291 patients. The angiographic outcomes of the study suggest that it may be possible to achieve at least comparable efficacy with a lower dose of everolimus than is used in commercialy available everolimus-eluting stents.[10] [11]
Advantages
The potential advantages these Bioabsorbable stents can offer over the traditional bare metal stents are:
- Reduced late stent thrombosis - the stent being absorbed completely leaves behind no stimulus to ignite a chronic inflammatory process and thus in turn reducing the rate of late stent thrombosis which is a major concern of the traditional stents.
- Short duration of post-stenting use of dual anti-platelet drugs.
- Obviates metal implants in vessels, leaves only healed natural vessel.
- Improved lesion imaging with CT and MRI unlike their bare metal counterparts.
- Facilitates reintervention (PCI and CABG)[12]
- Prevents the constrictive vascular remodeling postdilatation due to the scaffolding effect of the stent and after being absorbed completely allows late expansive luminal and vessel remodeling.
- Increased drug loading capabilities that will enable chronic drug release strategies.
- In the long run, eliminates mechanical stent deformity and strut fractures
Limitations
The bioabsorbable polymer stents have quite a few limitations in their own way:
- Strength is lower when compared to metallic counterparts, which can result in early recoil post implantation.
- Associated with a significant degree of local inflammation.
- These stents are radiolucent which may impair accurate positioning.
- The polymer alone has limited mechanical performance and a recoil rate of approximately 20%,which requires thick struts that impede their profile and delivery capabilities, especially in small vessels.
- Some experts opine that these stents can not be used in calcified lesions due to their lack of mechanical strength.[13]
Future applications
The probable future applications of the bioabsorbable stents are:
- Can be used in peripheral arteries like that of the femoral artery, tibial artery etc.,
- It's feasible to transfer genes that code key regulatory pathways inside the cells of the arterial wall using polymer stents as vehicles.
- Pediatric congenital heart diseases like Pulmonary artery stenosis. [14]
References
- ↑ http://circinterventions.ahajournals.org/content/2/3/255.full
- ↑ Waksman R (2006). "Biodegradable stents: they do their job and disappear". J Invasive Cardiol. 18 (2): 70–4. PMID 16446520. Unknown parameter
|month=ignored (help) - ↑ http://www.medscape.com/viewarticle/523241_2
- ↑ http://onlinelibrary.wiley.com/doi/10.1002/ccd.20727/abstract;jsessionid=8D3133482E4FE43C7025F17E0655A06F.d03t01?userIsAuthenticated=false&deniedAccessCustomisedMessage=
- ↑ http://circinterventions.ahajournals.org/content/2/3/255.full
- ↑ Morice MC, Serruys PW, Sousa JE; et al. (2002). "A randomized comparison of a sirolimus-eluting stent with a standard stent for coronary revascularization". N. Engl. J. Med. 346 (23): 1773–80. doi:10.1056/NEJMoa012843. PMID 12050336. Unknown parameter
|month=ignored (help) - ↑ Erbel R, Di Mario C, Bartunek J; et al. (2007). "Temporary scaffolding of coronary arteries with bioabsorbable magnesium stents: a prospective, non-randomised multicentre trial". Lancet. 369 (9576): 1869–75. doi:10.1016/S0140-6736(07)60853-8. PMID 17544767. Unknown parameter
|month=ignored (help) - ↑ Ormiston JA, Serruys PW, Regar E; et al. (2008). "A bioabsorbable everolimus-eluting coronary stent system for patients with single de-novo coronary artery lesions (ABSORB): a prospective open-label trial". Lancet. 371 (9616): 899–907. doi:10.1016/S0140-6736(08)60415-8. PMID 18342684. Unknown parameter
|month=ignored (help) - ↑ Serruys PW, Ormiston JA, Onuma Y; et al. (2009). "A bioabsorbable everolimus-eluting coronary stent system (ABSORB): 2-year outcomes and results from multiple imaging methods". Lancet. 373 (9667): 897–910. doi:10.1016/S0140-6736(09)60325-1. PMID 19286089. Unknown parameter
|month=ignored (help) - ↑ Meredith I, et al "Primary endpoint results of the EVOLVE trial: a randomized evaluation of a novel bioabsorbable polymer-coated, everolimus-eluting coronary stent" J Am Coll Cardiol 2012; DOI: 10.1016/j.jacc.2011.12.016
- ↑ Meredith IT, Verheye S, Dubois CL; et al. (2012). "Primary Endpoint Results of the EVOLVE Trial: A Randomized Evaluation of a Novel Bioabsorbable Polymer-Coated, Everolimus-Eluting Coronary Stent". J. Am. Coll. Cardiol. 59 (15): 1362–70. doi:10.1016/j.jacc.2011.12.016. PMID 22341736. Unknown parameter
|month=ignored (help) - ↑ http://www.theheart.org/documents/satellite_programs/intervcardiology/842901/transcript.pdf
- ↑ http://www.theheart.org/article/1144463.do
- ↑ Zartner P, Cesnjevar R, Singer H, Weyand M (2005). "First successful implantation of a biodegradable metal stent into the left pulmonary artery of a preterm baby". Catheter Cardiovasc Interv. 66 (4): 590–4. doi:10.1002/ccd.20520. PMID 16206223. Unknown parameter
|month=ignored (help)