An Era of Coronary Stents-Juniper Publishers
JUNIPER PUBLISHERS-OPEN ACCESS JOURNAL OF CARDIOLOGY & CARDIOVASCULAR THERAPY
The majority of percutaneous coronary
intervention cases are performed using drug eluting stents. Trials have
consistently demonstrated lower rates of in stent restenosis and repeat
revascularization with drug eluting stents when compared with bare metal
stents. Stent technology has improved over the decade with changes in
the thickness of stent struts, polymer coating and ease of stent
delivery to the desired location. Furthermore shorter duration of
antiplatelet therapy appears to be a promising option with the biolimus
A9 polymer free drug carrier stent. This is particularly beneficial in
patients who are deemed to be at high risk of bleeding such as those who
are prescribed coexisting anticoagulation. The development of the
bioresorbable stent allows the stent to be resorbed over time so that
the stent is no longer present in the vessel thus avoiding the problems
seen with conventional stents such as in stent restenosis.
Keywords: Percutaneous coronary intervention; Drug eluting stents; Bare metal stents; Restenosis rates; Biodegradable polymers
Abbreviations: DES: Drug Eluting
Stents; BMS: Bare Metal Stents; DAPT: Dual Anti Platelet Therapy; PCI:
Percutaneous Coronary Intervention; SES: Sirolimus Eluting Stent
Target lesion revascularization is reduced by 50-70%
with drug eluting stents (DES) when compared with bare metal stents
(BMS). This has led to the increased use of DES in patients. DES has an
antiproliferative drug coating inhibiting neointimal growth which is a
cause of restenosis. There are several types of DES available and vary
in the ability to prevent restenosis and stent thrombosis due to changes
in the drug and polymer coating. Unlike the BMS, DES requires the
prescription of prolonged dual anti platelet therapy (DAPT) to reduce
the rates of stent thrombosis. The duration of DAPT can however be
reduced to 3-6 months in certain circumstances such as those who require
surgery or patients at increased risk of bleeding [1]. First generation
DES includes those that release sirolimus or paclitaxel on a stent
platform of stainless steel.
These demonstrated lower restenosis rates when
compared to BMS. However late stent thrombosis was a concern with the
first generation DES and these have been largely been replaced by second
generation DES including those that release everolimus or zotarolimus
on a stent platform of cobalt chromium. Newer third generation stents
include polymer free stents or those that are resorbed over time so that
the stent is no longer seen in the vessel.
Stent thrombosis and restenosis can also be reduced
by using intravascular ultrasound guided stent implantation to ensure
that stents are well deployed and opposed to the vessel wall [11].
Target vessel revascularization is influenced by the presence of
diabetes mellitus, use of longer stents and stent deployment in smaller
vessels especially with the use of BMS [2,12,13]. In a study by Yeh et
al. [14] target vessel revascularization at 1 year occurred in 6.7% of
patients treated with a DES and 11%
of patients treated with a BMS. The number of patients needed
to treat to prevent one target vessel revascularization with DES
ranged from 6-80 patients. When the risk of restenosis with BMS
is ≤10%, the number needed to treat exceeds 25.
First generation drug eluting stents and bare metal stents
Sirolimus and paclitaxel eluting stents are first generation
DES. There were initial concerns about increased mortality
rates, myocardial infarction and stent thrombosis with the first
generation DES when compared to BMS. In an analysis of 18,023
patients who had percutaneous coronary intervention (PCI)
with a BMS or a sirolimus/paclitaxel eluting stent outcomes
were assessed over a 4 year period. Mortality rates were similar
in the three groups. Sirolimus eluting stents were associated
with the lowest risk of myocardial infarction p=0.030 versus
bare metal stent, p=0.045 versus paclitaxel eluting stents. The
risk of definite stent thrombosis at >30 days was increased with
paclitaxel eluting stents p=0.017 versus bare metal stent p=0.041
versus sirolimus eluting stents. Target lesion revascularization
was commonly encountered with paclitaxel eluting stents than
with sirolimus eluting stents, p=0.0021. Sirolimus eluting stents
therefore performed better than BMS and paclitaxel eluting
stents [2].
Sirolimus eluting stents and bare metal stents
Direct head to head trials with the sirolimus eluting stent
and BMS have shown reduced rates of revascularization with
sirolimus eluting stents. In a meta analysis of 1748 patients
enrolled in four randomized trials the safety of sirolimus eluting
stents were compared with BMS with regards to survival at 4
years. The survival rate at 4 years was 93.3% in the sirolimus
stent group and 94.6% in the bare metal stent group (P=0.28).
Rates of myocardial infarction and stent thrombosis were similar
in the two groups [12]. In a further analysis of 14 randomized
trials the rates of death, stent thrombosis, myocardial infarction
and revascularization rates were assessed with both stent types.
The combined risk of death or myocardial infarction was similar
for both groups. There was however a significant reduction in the
combined risk of death, myocardial infarction, or re-intervention
associated with the use of sirolimus eluting stents. Rates of stent
thrombosis did not differ between both groups early in follow up
however after the first year there was a slight increase in the rate
of stent thrombosis with sirolimus eluting stents [13].
Everolimus eluting stent and paclitaxel eluting stent
In a randomized study of 3687 patients the second generation
everolimus eluting stent was compared with the first generation
paclitaxel eluting stents. The 1 year composite rate of target
lesion failure, defined as cardiac death, target vessel myocardial
infarction, or ischemia driven target lesion revascularization was
analysed. Everolimus eluting stents were superior to paclitaxel
eluting stents with regards to the composite primary end point; 4.2% vs. 6.8% respectively P=0.001. There was a significant
reduction in the 1 year rate of ischemia driven target lesion
revascularization with everolimus eluting stents (P=0.001).
Rates of myocardial infarction and stent thrombosis were also
lower with the everolimus eluting stent than with the paclitaxel
eluting stent 1.9% and 3.1% P=0.02 respectively for myocardial
infarction; 0.17% and 0.85% P=0.004 for stent thrombosis.
Therefore the everolimus eluting stent was superior to the
paclitacxel eluting stent as there was a significant reduction in
target lesion failure and stent thrombosis at 1 year [6].
Everolimus and bare metal stents
Sirolimus eluting stents have been shown to be superior to
paclitaxel eluting stent [15] and therefore have generally used
as the standard to compare with second generation stents. In
the BASKET trial the efficacy of first generation SES (sirolimus
eluting stent) and BMS placed in large coronary arteries was
assessed. The efficacy of sirolimus eluting stents with the second
generation everolimus eluting stent was also analysed . At 2 year
follow-up, there were no significant differences in either of the
groups for the primary end point of death from cardiac causes or
nonfatal myocardial infarction. The primary end point occurred
in 2.6% of patients receiving the sirolimus eluting stent, 3.2%
in the everolimus group, and 4.8% in the BMS group. Stent
thrombosis rates were also similar in all 3 groups. The rates
of target vessel revascularization was significantly reduced
amongst patients receiving a DES when compared with a BMS,
3.7% for sirolimus eluting stents, 3.1% for everolimus eluting
stents and 8.9% for BMS. In patients requiring PCI of large
coronary arteries, the rates of death and myocardial infarction
were similar amongst all groups. Similar reductions in the rates
of target vessel revascularization were seen with both DES [16].
In the most recent trial of DES and BMS the NORSTENT study
assessed long term outcomes in 9013 patients undergoing PCI.
Second generation DES, zotarolimus or everolimus eluting stent
were compared with BMS. At 6 years the primary composite
outcome of death and non fatal myocardial infarction occurred
in 16.6% of patients receiving DES and 17.1% receiving BMS
(P=0.66). Repeat revascularization was encountered in 16.5%
and 19.8% respectively (P<0.001). Stent thrombosis rates were
lower with DES versus BMS; 0.8% and 1.2% respectively (P
0.049). Although rates of stent thrombosis were lower in the DES
group the incidence of overall stent thrombosis has reduced over
the decade due to improvements in stent design. Quality of life
measures such as the presence of anginal symptoms, frequency
of angina and physical limitations were similar amongst both
treatment arms [17].
Zotarolimus and everolimus eluting stents
Second generation zotarolimus and everolimus eluting
stents have shown reduced rates of restenosis, however, it is
unclear whether there are differences in efficacy and safety
between the two types of stents. In a randomized study, 2292 patients were assigned to treatment with either zotarolimus
or everolimus eluting stents. The primary end point of target
lesion failure, defined as a composite of death from cardiac
causes, myocardial infarction or clinically indicated target
lesion revascularization within 12 months was assessed. Repeat
angiography was performed in 20% of patients at 13 months to
assess the extent of in stent stenosis. The zotarolimus eluting
stent was non inferior to the everolimus eluting stent with
respect to the primary end point, which occurred in 8.2% and
8.3% of patients, respectively. The rate of stent thrombosis was
2.3% in the zotarolimus stent group and 1.5% in the everolimus
stent group (P=0.17). In-stent late lumen loss was 0.27±0.43
mm in the zotarolimus eluting stent group and 0.19±0.40 mm in
the everolimus stent group (P=0.08). There were no significant
differences in the primary outcomes with both stent types [7].
Third generation stents
Third generation stents include the promus premier stent
on a backbone of cobalt chromium, the biolimus A9 stent and
bioresorbable stents. In the LEADERS free trial the biolimus
A9 polymer free drug coated stent demonstrated superiority
over the gazelle BMS in patients who were at increased risk of
bleeding but required PCI. The biolimus A9 stent is polymer
free and elutes urimolimus in the coronary vessel wall within
1 month of implantation. Patients were randomized to receive
the gazelle BMS or the biolimus A9 stent followed by 1 month of
DAPT. The primary end point of death, myocardial infarction and
stent thrombosis occurred in 12.9% of patients who received a
BMS and was significantly lower in the patients who received
the biolimus A9 stent at 9.4%. Target lesion revascularization
was also lower with the biolimus A9 stent, 5.1% and 9.8% with
a BMS.
Therefore, in patients who are at high risk of bleeding
such as those who require concomitant anticoagulation for
conditions such as atrial fibrillation the biolimus A9 appears
to be a promising option [18]. It is important to note that over
60% of patients in the trial were deemed to be at increased
risk of bleeding based on being above > 75 years of age. In real
life practice shorter duration of DAPT is not often prescribed
based on age alone unless there are other factors to support
increased bleeding risk. Further trials with the biolimus A9 stent
and the promus everolimus eluting stent have demonstrated
non inferiority. In the NOBORI trial the rate of target vessel
revascularization at 1 year was the same with both stent
types. Definite stent thrombosis was also similar amongst
groups, 0.25% for biolimus and 0.06% for promus p=0.18 [19].
Therefore, the biolimus A9 stent was non inferior to the promus
everolimus eluting stent.
Newer stents such as the bioresorbable scaffold stent
elutes
everolimus and has thicker stent struts and take 4-5 years
before it is fully resorbed. It is believed to reduce restenosis
as stent struts are resorbed over time leaving no substrate for
restenosis. The bioresorbable stent has shown similar rates of target
lesion revascularization, target lesion failure, myocardial
infarction and death when compared to the everolimus eluting
metallic stent. However, definite or probable stent thrombosis
rates were higher in patients treated with the bioresorbable
stent specifically within the first 30 days of deployment [20].
The stent maybe a viable option in younger patients who may
potentially require a coronary artery bypass graft surgery in
the future where a standard DES may prevent optimal graft
positioning in the vessel.
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