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this we use the highly deliverable Pro-Kinetic energy bare metal stent
as a platform for orsiro. The Pro-Kinetic energy cobalt–chromium stent
platform has a double-helix stent design that allows for increased
flexibility without compromising scaffolding or fatigue resistance. The
helical meanders give flexibility to the stent for excellent delivery and
allow for a smooth crimped surface without fish scaling. The longitudinal
connectors provide stability to the double-helical structure for optimal
scaffolding and support without sacrificing flexibility. The wedge-shaped
transitions at the stent ends allow for scaffolding and flexibility
throughout the entire length of the stent. All of these features of the
double-helix stent design translate into increased trackability,
crossability and ability to conform to the vessel wall. The cobalt–
chromium stent material allows for thin struts while maintaining optimal
radial strength and radiopacity. orsiro is noted to have the thinnest
struts compared with other Des, specifically down to 60
m
m, varying
with the available stent diameters of 2.25–4.0 mm and lengths of 9–
30 mm. This ensures minimal wall injury, leading to better patient
outcomes. Adding the polymer to the thin struts of the Pro-Kinetic
energy stent platform, the total thickness of the stent struts of stents
with a nominal diameter of up to 3.0 mm is 71
m
m – significantly lower
than the thickness of competitors, including Xience (Abbott Vascular,
Abbott Park, iL, us) at 95
m
m and endeavor resolute (Medtronic,
Minneapolis, Mn, us) at 99
m
m. The advanced stent crimping technology
provides a low crossing profile (0.99 mm) and the optimised delivery
system allows for higher-pressure inflations (mean burst pressure
24–30 atm depending on diameter; rated burst pressure 16 atm).
Pre-clinical Results
The safety of orsiro was demonstrated in animal studies. A safety study
of both the orsiro and cypher (cordis corporation, Bridgewater, nJ, us)
stents looking specifically at histology and quantitative coronary
angiography at four, 12 and 26 weeks in pig coronaries demonstrated
that orsiro with PLLA + sirolimus had a better safety profile than cypher;
the same was seen with an overdose model. furthermore, an overlap
safety study looking at four-week quantitative coronary angiography and
histology showed that there was no difference in safety profile and drug
effect in the overlapping region of orsiro. A pharmacokinetic study up to
three months showed comparable blood levels and coronary tissue
concentrations to a -limus-based Des together with low organ tissue
concentrations. A long-term polymer degradation study evaluating
histology and histomorphometry up to three years was performed,
demonstrating excellent biocompatibility and a lack of late increase in
inflammation (data on file, Biotronik Ag, under publication).
Clinical Programme
orsiro is supported by a comprehensive clinical programme consisting
of a series of trials sharing the family name BiofLoW. BiofLoW-i is the
first-in-man trial with 30 patients conducted in 2009 under the
leadership of Professor Martial hamon (university hospital of caen,
france). The excellent results
8
of the BiofLoW-i study (clinicalTrials.gov
identifier: ncT01214148) are on par with other first-in-man trials of
contemporary Des and was used for the ce-mark application. The
results also served as input to the design of BiofLoW-ii
(clinicalTrials.gov identifier: ncT01356888), a pan-european randomised
controlled trial with 440 patients comparing the orsiro with the Xience
Prime stent that started enrolment in July 2011. BiofLoW-iii is a global,
open-label registry that will enrol 1,000+ patients and will also look at
pre-specified subgroups including diabetes, small vessels, acute
myocardial infarction and chronic total occlusion. enrolment started in
August 2011.
Conclusion
in conclusion, orsiro brings a new strategy to the treatment of
coronary artery disease with a hybrid solution of active and passive
components. The ProBio passive coating provides a seal on the
metal surface of the stent and the Biolute active coating
provides controlled drug release, with both components preventing
an increased inflammatory response. The stent backbone is the
Pro-Kinetic energy platform, which provides flexibility with a
double-helix stent design and thin struts. The clinical performance,
which has been assessed in initial
in vitro
and
in vivo
studies, will be
further demonstrated in forthcoming publications.
Orsiro – The First Hybrid Drug-eluting Stent for Superior Patient Outcomes
5
1.
Kalnins A, erglis u, Dinne A, et al., clinical outcomes of
silicon carbide coated stents in patients with coronary artery
disease,
Med Sci Monit
, 2002;8:16–20
2.
Amon M, Bolz A, schaldach M, improvement of stenting
therapy with a silicon carbide coated tantalum stent,
J Mat Sci
Materials in Med
, 1996;7:273–8.
3.
fan W, Johnson DM, feldman MD, et al., Metallic stents
coated with bioabsorbable polymers,
Cardiac Interventions
Today
, 2009;7:42–9.
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Zilberman M, eberhart rc, Drug-eluting bioresorbable
stents for various applications,
Annu Rev Biomed Eng
,
2006;8:153–80.
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fischell TA, Dishmon D, elhaddi A, et al., The perfect drug-
eluting stent,
Cardiac Interventions Today
, 2009;7:29–36.
6.
Parry TJ, Brosius r, Thyagarajan r, et al., Drug eluting stents:
sirolimus and paclitaxel differentially affect cultured cells and
injured arteries,
Eur J Pharmacol
, 2005;524:19–29.
7.
Wessely r, Blaich B, Belaiba rs, et al., comparative
characterization of cellular and molecular anti-restenotic
profiles of paclitaxel and sirolimus. implications for local drug
delivery,
Thromb Haeomst
, 2007;97;1003–12.
8.
hamon M, first-in-man experience with the Des orsiro in the
treatment of patients with single de novo coronary artery
lesions (BiofLoW-i), Late breaking first-in-human trials
session, euroPcr 2011, Paris, May 18 2011
Figure 4: Neointimal Proliferation after Implantation of
Three Different Coating Matrix Formulations
Durable polymer A
+ sirolimus
n=11
Durable polymer B
+ sirolimus
n=10
BIOLute*
n=10
1
0
2.23
1.80
1.27
2
2
4
Intimital area (mm
2
)
*The PLLA and Sirolimus matrix used on Orsiro.
The BIOlute formulation shows the lowest proliferation at 28 days.
Figure 5: Drug Elution Curve
0
0
20
40
Time (days)
Percent drug released
60
80
100
10
20
30
40
50
60
70
80
90
100
in vivo
pre-clinical pharmacokinetic studies in minipig coronary arteries show a controlled
drug release over the course of three months.
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