gershlick_subbed_Cardiology_book_temp 27/10/2009 10:26 Page 89
Drug-eluting Stents—Issues and Developments
Figure 2: Molecular Structure of Sirolimus, Everolimus, Biolimus, Zotarolimus, Tacrolimus, and Pimecrolimus
Everolimus Sirolimus Tacrolimus Pimecrolimus
OCH CH OH OH
OCH OH CH CI2 2
3 2
Zotarolimus Biolimus
H
N N
OCH CH OR
2 2
CH
3
NN
H C
O
3
H
O OH
N
O
O
CH -H OO
3 2
OH
H C
3
CH
O 3
CH
3
OCH
CH
O 3
3
OCHH CO
4 33
O9CH 5
3
3
6 8 10
H C
3
7 11
2
O O OH 12
H C Paclitaxel O
3
1 13
14
O
N
H C
OO15
3 OH
OCH
CH29 3
3
16O
17
O
O28 H
H C
318
19
N
OHO O
20FK binding 21
27
O
protein site
CH
22
23 3
26 H
mTOR- O
24 O25 HO
O
CHbinding site
3
OH
O
O
Zotarolimus the Endeavor stent failed to meet its non-inferiority end-point in terms of
A third descendant of the Limus family that also has a change on late lumen loss. Of note, the rates of death, myocardial infarction (MI),
position 40 and that is used on coronary stents is zotarolimus (ABT- and target vessel revascularization were equal in both groups.
28
A
578, Abbott Pharmaceuticals, Abbott Park, Ill), which likewise has possible explanation for the lack of non-inferiority of the Endeavor stent
antiproliferative and anti-inflammatory effects, but zotarolimus is might be the rate of elution. The Cypher stent elutes 75% of its drug
suggested to have higher tissue retention than the SES (see Figures 1 within the first 10 days; in the Endeavor stent this took only two days.
and 2). Of note, data on endothelial function after stent placement in
porcine coronaries showed a normally functioning endothelium one Another zotarolimus-eluting device is the Zomaxx TriMaxx™ stent
and three months after zotarolimus-eluting stent implantation, (Abbott Pharmaceuticals, Abbott Park, Illinois), which has a trilayer
whereas a dysfunctional endothelium was observed after both Cypher pharmacoat that consists of a phosphorylcholine basecoat and
and Taxus implantation.
25
topcoat wrapped around a zotarolimus laye with elution rates similar
to the Cypher stent. The platform used was a stainless steel/
In the Randomized Comparison of Zotarolimus- and Paclitaxel-eluting tantalum/stainless steel triplex stent. Although the four-month results of
Stents in Patients With Coronary Artery Disease (ENDEAVOR) I and II trials, the Zomaxx-intravascular ultrasound (IVUS) trial (n=40), which showed a
the phosphorylcholine polymer-based cobalt-alloy Driver coronary stent late loss of 0.20mm, were promising, its manufacturer Abbott recently
(Medtronic Vascular, Santa Rosa, California) loaded with zotarolimus announced it would discontinue the Zomaxx program after
proved to be superior to BMS in both angiographic and clinical the disappointing results of the Zomaxx-I trial. At nine months, the
end-points.
26,27
Recently presented two- and three-year follow-up data of Zomaxx stent was associated with a significantly higher late loss and
the ENDEAVOR I and II trials proved sustained superiority in the reduction binary restenosis rate compared with the Taxus stent.
29
of target lesion revascularization (TLR), with remarkably low rates of total
stent thrombosis (0.3%) and no cases of stent thrombosis after 30 days. Paclitaxel
The ENDEAVOR III trial was a prospective randomized comparison of the Although not a member of the Limus family, the PES (Taxus, Boston
Endeavor zotarolimus-eluting stent and the SES (n=436). At eight months, Scientific, Natick, Mass) was the second DES to receive FDA approval
US CARDIOLOGY 89