Coronary Angioplasty and Drug-Eluting Stents - Applications of Biotechnology in Cardiovascular Therapeutics - page 302

retain, and release drug or to act as a barrier to drug delivery depends on clot
geometry and strut position in clot relative to the vessel wall. Clot between artery
and stent can reduce uptake tenfold, whereas clot overlying the stent can shield
drug from washout, increasing uptake. These assumptions were confirmed and
predictions were validated in a novel rat model that introduces thrombosis within
stented aortas where nonocclusive thrombus acts as capacitive space for drug and
shifts drug levels to decrease tissue uptake twofold (Hwang et al. 2005 ). Thus,
the thrombus formed on stents creates large variations in drug uptake and can act
to either increase or decrease wall deposition according to the clot and stent
geometry. Arterial deposition of drug from stents deployed in clots will be highly
variable and unpredictable unless the clot can be adequately controlled or
removed.
Use of Magnetized Cell Lining to Prevent Clotting of DES
A novel approach to prevent blood clotting in DES is based on magnetizing
endothelial progenitor cells from the patient's blood, which are quickly drawn to
magnetically coated stents (Pislaru et al. 2006 ). Cultured porcine endothelial cells,
extracted from blood, were labeled with endocytosed superparamagnetic iron oxide
microspheres. After the stent was implanted, the iron-tagged cells were introduced
back into the blood vessel to test how well the magnetized stents captured the cells.
Because the endothelial progenitor cells naturally counteract blood clot formation,
their swift magnetically guided arrival to the stent may reduce the chances of blood
clot formation by lining the site fully and quickly. Results from preclinical testing
are encouraging. There was a 6- to 30-fold improvement in the magnetized stents'
performance in capturing the healing endothelial cells, compared to the standard
stents' ability to do so.
Long-Term Safety Studies of DES
The trend in medicine in the USA and Europe is evidence-based medicine, which
is use of current best evidence in making decisions about the care of individual
patients. Successful implementation of evidence-based medicine in the develop-
ment of high-risk medical devices requires a methodical scientific approach. In
case of DESs, even when research evidence is available from randomized con-
trolled studies, it can be difficult to translate clinical evidence into regulatory and
clinical decisions (O'Dwyer 2004 ).
One study has investigated the frequency of off-label and untested use, 1-year
repeat target vessel revascularization, and composite of death, myocardial infarc-
tion, or stent thrombosis at in-hospital follow-up and during 1 year of follow-up
(Beohar et al. 2007 ). The results show that in contemporary US practice, off-label
and untested use of DES is common. Compared with standard use, relative early
safety is lower with off-label use, and the long-term effectiveness is lower with
both off-label and untested use. However, the absolute event rates remain low.