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Introduction
Coronary stent implantation is the standard therapy during
percutaneous coronary intervention (PCI) to prevent early- and late
recoil and to reduce the rate of recurrent stenosis. Drug eluting
stents (DES) could further reduce the rate of restenosis, but at the
expense of delayed re-endothelialisation
1-4
. But exactly this delayed
re-endothelialisation process may be the foremost reason for the
increased risk of late stent thrombosis after drug eluting stent, even
very late (1-3 years) after stent deployment
5,6
. This leads to the
concept of passive coatings in order to enhancing the endothelialisation
process to bypass this risk
7-10
.
The proliferation of smooth muscle cells as the dominant
mechanism of restenosis after stent deployment is suspected to be
triggered by interactive processes at the interface between the stent
and the biological environment. Today, the majority of stents consist
of uncoated 316L medical grade stainless steel or cobalt chromium
alloys. But stainless steel and other metals show unfavourable
effects when they come in contact with blood constituents like
proteins and cells (Figure 1)
11,12
. These interactions betweens
proteins and cells with the implant are the origin of irreversible
processes involved in in-stent restenosis: 1) the initiatory platelet
aggregation including synthesis and activity of fibrinogen and
thromboxane A2, mitogenic activity, leukocyte activation, and
complement activation13; 2) endothelial dysfunction promoting
vasoconstriction and its sequelae; 3) exposure of medial cells to
circulating mitogens
14
and increased smooth-muscle-cell
proliferation and extracellular matrix formation
15
. The activation,
cleavage or deformation of proteins triggers further biochemical
reactions that result in loss of implant functionality. Stent surface
modifications (e.g. coatings) should therefore inhibit unwanted
interactions between stent and surrounding tissue
16
.
The concept of Anti-hCD-34 coating capturing circulating CD34+
progenitor cells to the luminal stents struts in order to rapidly
differentiating into a functional endothelial layer (Pro-healing
concept) have been encouraging
7
, but comparable results have
also been documented in stents increasing early endothelial nitric
oxide release in order to promote early endothelial growth and
function as strategy against restenosis
17-19
.
Silicon carbide is an amorphous, hydrogen-rich, phosphorous-
doped modification (a-SiC:H) with superior biocompatibility
including significant lower fibrinogen and leukocyte adhesion to
platelets
20-22
. Moreover, silicon carbide showed significant lower
protein adhesion and increased rapid endothelialisation leading to an
improved functional endothelial layer
23
. In clinical studies, silicon
carbide coated stents proved to have significant reduced
complication rates when compared to uncoated stainless steel
stents
24-27
, however in the TRUST-study a late catch-up have been
recognised at 9-months follow-up in patients with unstable angina
28
.
Because stents with reduced stent strut thickness maintained radial
strength due to cobalt-chromium alloys, as well as demonstrated
supplementary effects and encouraging clinical outcomes, we
investigated the clinical performance, efficacy, complication rate
and incidence of recurrent stenosis after implantation of a new
designed silicon carbide coated cobalt-chromium stent in a clinical
registry of consecutive CAD patients with indication for
percutaneous coronary interventions.
Methods
Study population
All patients with symptomatic coronary artery disease admitted to
the Department of Cardiology and with an indication for
percutaneous coronary intervention (intention-to-treat) were
enrolled into the study. Enrolment for the PRO-Heal registry took
place between February 2006 and June 2007. In this study,
patients were eligible for enrolment if they had experienced at least
one > 70% symptomatic coronary stenosis (visual estimate) in
a epicardial coronary artery > 2,25 mm with indications for
coronary stent implantation. Patients with known contraindications
to aspirin, heparin, or ticlopidine/clopidogrel were excluded from
the study. All patients gave written informed consent, and the study
was conducted according to the principles of the Declaration of
Helsinki. Clinical follow-up at 6-months was requested in all
patients enrolled. Due to regulatory and ethical reasons,
angiographic follow-up was only requested in those patients with
recurrent or new-onset clinical symptoms or in patients with
remaining non-target vessel lesions with indication for additional
angioplasties.
Definitions
Data collection.
Case report forms with pertinent information
concerning patients’ demographics, clinical, angiographic, and
procedural data were recorded prospectively on standardised forms
and entered into a computerised database. We collected
demographic and baseline data on the following: gender, age,
history of diabetes, left-ventricular ejection fraction, severity and
extend of lesion distribution resulting from coronary artery disease,
stenosis morphology, actual myocardial infarction (ST-STEMI) and
Figure 1. Scanning electron microscopic images. The upper row shows
a SiC:H - coated device, the lower row a bare metal stent, before (left)
and after (right) blood contact. Note: nearly no fibrin thrombus
formation was detected after 120 minutes of blood contact, while the
bare nitinol stent showed a dense and organised fibrin network with
included platelets and red blood cells.