Chinese Medicine, 2009, 1, 1-6
Published Online September 2009 in SciRes (www.SciRP.org/journal/cm)
Midterm Outcomes of Prospective, Randomized,
Single-Center Study of the Janus Tacrolimus-Eluting
Stent for Treatment of Native Coronary Artery Lesions
ABSTRACT
From February 20, 2006 to August 26, 2006, a total of 200 patients were enrolled and randomly assigned to receive
either Janus stent (n=100) or bare metal stent (Tecnic Carbostent, n=100). All patients were administered with clopi-
dogrel for 4 months and aspirin for life long after stenting. Baseline clinical and angiographic characteristics were
comparable between the two groups. AMI was present in 37% of patients with Janus and 36% with Tecnic Carbostent.
At an average of 246-day follow-up, major adverse cardiac events (MACE) was 6% with the Janus stent and 15% with
the Tecnic Carbostent (P=0.038). Primary events included 1 cardiac death, 1 myocardial infarction (MI) due to
subacute stent thrombosis and 13 target lesion revascularizations (TLR) due to restenosis in patients with Tecnic Car-
bostent and 6 TLR due to restenosis in patients with Janus stent. Although all patients had discontinued clopidogrel for
an average of 126 days, there was no additional thrombotic event in the two groups.
Keywords: drug-eluting stent, acute myocardial infarction, angioplasty, transluminal, percutaneous coronary
1. Introduction
Drug-eluting stent (DES) has been reported to dramati-
cally reduce the incidence of restenosis and target lesion
revascularization (TLR), and is widely used in clinical
practice in recent years. However, controversies remain
with regard to the long-term efficacy and safety for the
first generation DES1. Pathological findings had indi-
cated that polymer based DES delayed vessel healing,
which might lead to late severe adverse events such as
in-stent thrombosis. The permanent existence of non-
degradable polymer coatings, which promote local vessel
inflammation, is considered as one of the leading causes
reducing vessel healing. The Janus tacrolimus-eluting
stent (SORIN, Italy), a novel DES without polymer
coating, is deemed capable to eliminate the adverse ef-
fects of non-degradable polymer coatings of DES. Pre-
liminary clinical outcomes from Jupiter I and II studies
demonstrated that Janus stent was as safe as bare metal
stent (BMS) and tended to reduce restenosis rate. How-
ever, the study population in Jupiter I and II comprised
of only low to mid-risk patients and lesions. We con-
ducted a prospective, randomized, single-center study
aiming at evaluating the safety and efficacy of Janus
stent for treating coronary artery disease in “real world”
clinical practice of percutaneous coronary intervention
(PCI) for the first time.
2. Methods
2.1. Study Population
Between February 20, 2006 and August 26, 2006, a total
of 200 patients with symptomatic or documented myo-
cardial ischemia, including acute myocardial infarction
(AMI), were enrolled in this prospective, randomized
study. Patients were considered eligible for enrollment if
they were: fit for coronary stent implantation; to be
treated exclusively with one kind of stent, no more than
3 stents for one target vessel (or total length of stents ≤85
mm), and providing written informed consent. The major
exclusion criteria were in-stent restenosis lesion, graft
lesion, not eligible for DES implantation, such as intol-
erant of anti-platelet treatment or planned to undergo
surgery, and administration of IIb/IIIa antagonist.
2.2. Study Protocols
Patients were randomly assigned to receive Janus stent

Y. L. HAN ET AL. 2
(n=100, Janus group) or Tecnic Carbostent (SORIN,
Italy, n=100. Tecnic group) according to the computer
generated randomization list. A 300-600 mg loading
dose clopidogrel (Plavix, Sanofi aventis) were given for
all patients at admission. Coronary angiography and ste-
nting were performed according to the standard tech-
niques2. After stent implantation, all patients received
dual antiplatelet therapy: aspirin 300 mg per day for the
initial one month continued with 100 mg per day for
life-long and clopidogrel 75 mg per day for 4 months. In
patients with AMI, the antiplatelet regimen was mostly
the same except clopidogrel 150 mg per day for the ini-
tial one week. Clinical follow-up was performed at 1-, 6-,
12- and 24-month and follow-up angiography was per-
formed at 9 months after the index procedure.
2.3. End Points and Definitions
The primary end point was the 12-month rate of major
adverse cardiac events (MACE), defined as the compos-
ite of cardiac death, nonfatal myocardial infarction (MI)
or TLR. The secondary end points were 9-month rate of
angiographic in-stent restenosis and MACE at 24-month.
MI was defined either as the development of pathologi-
cal Q waves in at least 2 contiguous leads with or with-
out elevated cardiac enzymes or, in the absence of path-
ological Q waves, as an elevation in creatinine kinase
levels to greater than twice the upper limit of normal in
the presence of an elevated creatinine kinase-MB level.
TLR was defined as repeat revascularization for ische-
mia owing to stenosis ≥50% of the lumen diameter any-
where within the stent or within the 5-mm borders
proximal or distal to the stent. Restenosis was defined as
the diameter stenosis of ≥50% of the target lesion.
2.4. Statistical Analysis
Categorical discrete variables were compared by the x2
test or the Fisher exact test when appropriate. Continu-
ous variables were presented as mean±standard deviation
(SD) and were compared with the use of the Student’s t
test. A P value <0.05 was considered statistically sig-
nificant. Data were analyzed using SPSS 10.0.
3. Results
3.1. Baseline Clinical Characteristics
The baseline clinical characteristics of the two groups
were well matched (Table 1). Onset of AMI within 24
hours occurred in 37 patients in Janus group (including 4
non-ST segment elevation MI) and in 36 in Tecnic group
(including 3 non-ST segment elevation MI). The propor-
tions of acute coronary syndromes (ACS) were 78% in
Janus group and 75% in Tecnic group, respectively.
3.2. Baseline Angiographic Characteristics
The target lesions (113 vs 122) and target vessels (107 vs
113) were similar between the two groups. Lesion char-
acteristics of the two groups were well matched (Table
2). Multivessel disease was present in 7% of patients in
Janus group and 13% of patients in Tecnic group (All
were dual vessel disease, P>0.05).
Table 1. Baseline clinical characteristics
Janus (n=100) Tecnic(n=100) P value
Age (years） 57.94±11.52 58.79±11.26 NS
Male (%) 75 78 NS
Smoking (%) 55 62 NS
Hypertension (%) 58 57 NS
Diabetes (%) 27 17 NS
Family history of CAD (%) 12 14 NS
AMI within 24 hours (%) 37 36 NS
Killip class III−IV 4 2 NS
Unstable angina (%) 41 39 NS
LMWH before PCI (%) 11 14 NS
LMWH post PCI (%) 47 46 NS
Hypertriglyceridemia (%) 35 40 NS
Hypercholesteremia (%) 31 41 NS
NYHA class III−IV (%) 19 20 NS
CAD: coronary artery disease. AMI: acute myocardial infarction. LMWH: low molecular weight heparin. PCI: percu-
taneous coronary intervention. NYHA: New York Heart Association. NS: not significant.

Y. L. HAN ET AL.3
Table 2. Baseline angiographic characteristics
Janus (n=100) Tecnic(n=100) P value
Reference vessel diameter (mm) 3.08±0.36 3.07±0.37 NS
Lesion length (mm) 27.0±10.30 27.1±11.12 NS
Diameter stenosis (%) 89.9±11.89 89.3±13.10 NS
Location of target lesions (n (%))
LM 3(2.7) 4(3.3) NS
LAD 69(61.1) 61(50.0) NS
LCX 17(15.0) 25(20.5) NS
RCA 24(21.2) 32(26.2) NS
ACC/AHA lesion type (n (%))
A/B1 lesions 6(5.3) 7(5.7) NS
B2/C lesions 107(94.7) 115(94.3) NS
Bifurcation lesions (n (%)) 45(39.8) 36(29.5) NS
CTO lesions (n (%)) 11(9.7) 10(8.2) NS
Thrombotic lesions (n (%)) 25(22.1) 17(13.9) NS
Ostial lesions (n (%)) 5(4.4) 3(2.4) NS
Small vessel lesions (≤2.75 mm) (n (%)) 12(10.6) 14(11.5) NS
Long lesions (≥20 mm) (n (%)) 81(71.7) 71(58.2) NS
99%−100% diameter stenosis (n (%)) 48(42.5) 48(39.3) NS
LM: left main. LAD: left anterior descending coronary artery. LCX: left circumflex coronary artery. RCA: right coro-
nary artery. CTO: chronic total occlusion. ACC/AHA: American College of Cardiology/American Heart Association.
NS: not significant.
Table 3. Stent implantation and procedural results
Janus (n=100) Tecnic(n=100) P value
Mean stent diameter (mm) 3.16±0.38 3.17±0.42 NS
Mean stent length (mm) 30.0±11.56 30.5±14.94 NS
Stents per lesion 1.07±0.28 1.11±0.31 NS
Stents per patient 1.22±0.82 1.35±1.08 NS
Maximum deployment pressure (kPa) 1530.0±375.9 1509.7±314.1NS
2.5 mm diameter stent (n (%)) 11(9.0) 12(8.9) NS
2.75 mm diameter stent (n (%)) 4(3.3) 11(8.1) NS
3.0 mm - 4.0 mm diameter stent (n (%)) 107(87.7) 112(83.0) NS
Stent overlapping (n (%)) 17(13.9) 21(15.6) NS
Post-dilatation (n (%)) 78(63.9) 81(60.0) NS
Direct stenting (n (%)) 25(20.5) 22(16.3) NS
Kissing balloon (n (%)) 13(10.7) 10(7.4) NS
Distal protective device (n (%)) 0(0) 1(1) NS
Procedural success (n (%)) 100(100) 100(100) NS
NS: not significant.

Y. L. HAN ET AL. 4
3.3. Procedural Results
There were totally 235 target lesions in 220 target vessel
of 200 observed patients underwent coronary stenting.
The procedure and device-deployment success rates
achieved 100% in the two groups. Procedural results
were similar for the two groups (Table 3). The maximum
total stent length in one vessel was 81 mm in patients
implanted with the Janus stent and 71 mm in patients
implanted with Tecnic carbostent (overlapped by 3
stents). Stents with small diameter (2.5-2.75 mm) ac-
counted for 12.3% in Janus group and 17.0% in Tecnic
group (P>0.05).
3.4. Overall Clinical Outcomes
Up to January 30, 2007, all patients were clinically fol-
lowed up for an average of (246±48) days (ranged 150 to
340 days). All the patients discontinued clopidogrel at
the end of the fourth month after PCI according to study
protocol. The mean interval from the discontinuation of
clopidogrel was (126±46) days (ranged 34 to 220 days).
Primary events occurred in 15 patients in Tecnic group,
including 1 cardiac death due to cardiac rupture secon-
dary to anterior AMI, 1 AMI caused by subacute in-stent
thrombosis, 12 repeat PCI and 1 CABG due to in-stent
restenosis, so the overall and stent-related MACE rates
were 15% and 14%, respectively. In Janus group, there
were 6 primary events of repeat PCI due to in-stent
restenosis, so the overall and stent-related MACE rates
were all 6%. The overall MACE rate was significantly
lower in Janus group as compared with Tecnic group
(6% vs 15%, P=0.038). For the TLR and stent-related
MACE, there was an obvious tendency of lower inci-
dence associated with the Janus stent but not statistically
significant (6% vs 14%, P=0.059).
3.5. Clinical Outcomes of AMI Subgroup
For the subgroup of AMI patients who underwent emer-
gent PCI within 24 hours of symptom onset, the mean
clinical follow-up was (250±46) days (ranged 154 to 323
days) in Janus group and (243±52) days (ranged 150 to
340 days) in Tecnic group, respectively. There was no
death or any thrombotic event in 37 patients in Janus
group except 3 repeat PCI due to in-stent restenosis. In
36 patients in Tecnic group, there were 4 primary end
points, including 1 cardiac death, 1 MI caused by
subacute in-stent thrombosis and 2 repeat PCI due to in-
stent restenosis. The incidence of death or MI was simi-
lar between the two groups (0 vs 2%, P=0.24). Although
all patients had discontinued clopidogrel, there was no
additional death or thrombotic event in the two groups.
4. Discussion
Controversies about DES regarding its late clinical out-
comes were emerged and spread after the initial years of
inspiritment. Because of the growing concern that de-
layed endothelialization after implantation of a DES may
cause late stent thrombosis, prolonged dual antiplatelet
therapy with clopidogrel and aspirin is currently recom-
mended after DES implantation. Unfortunately, even
with 6 months or longer period of dual antiplatelet ther-
apy, the incidence of late thrombosis or deadly cardiac
events after DES implantation were still higher than
those after BMS implantation3. Therefore, it is important
to develop a new generation of DES which might de-
crease the restenosis not at the expense of safety.
The Janus tacrolimus-eluting stent is one of such new
generation DES. As the platform of Janus stent, the Tec-
nic Carbostent is coated with Carbofilm to increase the
biocompatibility and hemocompatibility4,5.
Phantom IV
study demonstrated the efficacy and safety of Tecnic
Carbostent. In that study, there was no death or MI at
6-month clinical follow-up after Tecnic Carbostent im-
plantation, and the angiographic restenosis rate was
14%6. Of the 100 patients received the Tecnic Carbostent
in the present study, the stent related thrombotic events
rate was only 1% at an average of 8-month follow-up,
which confirms that the Tecnic Carbostent is a safe BMS
platform. Having kept the structural features of the Tec-
nic Carbostent, the Janus stent is coated with tacrolimus,
an immunosuppressant, which was demonstrated to be
efficient in inhibiting neointima hyperplasia of porcine
coronary artery7,8. Differed from the first generation DES,
i.e. Cypher and TAXUS, Janus stent has some unique
features. First, drugs are loaded in the embedded reser-
voirs on the outer stent surface, which enables drugs re-
leasing directly to vessel wall without being washed
away in the bloodstream. Second, there is no polymer
coating in Janus stent, which may decrease the potential
risks of late in-stent thrombosis caused by unabsorbable
polymer coatings of traditional DES9.
Jupiter I study, the first-in-man registry of Janus stent,
enrolled 58 patients. Of whom, 19% were ACS (includ-
ing 6.9% of AMI). The target lesions included only 27%
complex lesions of type B2/C with (11.5±5.9) mm of
lesion length and (70.3±14.9)% of stenosis diameter. The
randomized, controlled Jupiter II study presented at 2005
TCT showed that the total rate of MACE in the 157 pa-
tients of Janus group was 7.6%, in which 6.4% of MACE
was related to the stent, suggesting Janus stent having
better clinical effects and safety. However, ACS ac-
counted for only 27.6% of patients in Janus group in
Jupiter II. Furthermore, ST segment elevation MI
(STEMI) within 7 days and non-ST segment elevation
MI (NSTEMI) within 3 days were all excluded in Jupiter
II. It also excluded those with complicated lesions such
as ostial lesions, left main diseases, chronic total occlu-
sions (CTO), bifurcations, lesion in small vessels (refer-
ence diameter ≤ 2.75 mm), long lesions (lesion length

Y. L. HAN ET AL.5
>20 mm) and thrombotic lesions. Complex lesions of
Type B2/C took only 34.9%. Because of the relatively
simple lesion type, 75.9% of patients underwent suc-
cessful direct stenting. Compared with Jupiter I and II
studies, the population in the present study included 78%
of ACS patients. The target lesions included many com-
plicated lesions of high risk, such as left main or ostial
lesions, thrombotic lesions, CTO, bifurcations, long le-
sions, small vessel lesions with 2.5 mm in diameter.
Some of the patients were highly endangered by some
risk factors of coronary heart disease, for instance, dia-
betes, smoking and hypertension, which generally re-
flected the “real world” of clinical PCI daily practice.
Despite of the higher risk for clinic and restenosis in
subjects of present study, the incidence of MACE was
6% without occurrence of death or thrombosis in Janus
group during the mean 8-month follow-up. Besides, as
compared with the Tecnic group, incidence of MACE
was dramatically reduced (P=0.038). The rate of stent
related MACE had an obvious lower tendency in Janus
group but no statistical significance (P=0.059). The
above result was similar to that of Jupiter I and II, and
further confirms the safety and clinical efficacy of Janus
stent. Different from the present study, Jupiter II did not
achieve statistical differences in the total rate of MACE,
which might mainly due to the differences in study
population. The enrolled patients in Jupiter II were
mostly at lower risk for thrombosis. It has been reported
that the effect of DES in reducing restenosis is not supe-
rior to that of BMS for lesions with length <15 mm and
vessel diameter >2.8 mm10. Moreover, Tecnic stent itself
has certain antithrombotic function which may reduce
the thrombosis related events in the control group in
Jupiter II, in which late lumen lost was only 0.64 mm,
and the incidence of in-stent restenosis was 14.8% in
patients implanted with Tecnic stent. This was probably
the reason for Jupiter II to come to the conclusion that
the total incidences of MACE and stent related MACE in
Janus group were not significantly lower than those in
Tecnic group.
Up to now, the safety of DES implantation in primary
PCI is uncertain. The randomized Typhoon trial showed
that sirolimus eluting stent for treatment of STEMI was
efficient in reducing MACE and TLR compared with
BMS, but not beneficial for death, MI or in-stent throm-
bosis11. In the present study, more than a third of study
population were those with STEMI or NSTEMI under-
going emergent PCI within 24 hours of symptom onset,
which were excluded in Jupiter I and II study. For 37
AMI patients (including 33 STEMI) in Janus group, no
acute, subacute or late thrombosis occurred at an average
8-month follow-up, suggesting Janus stent is safe in
treating AMI.
It was reported that incomplete endothelialization
even appeared 1-2 years after implantation of Cypher or
TAXUS in some cases12. The reports of very late in-stent
thrombosis (>1 year) after DES implantation were also
not rare13. Long-term dual antiplatelet therapy may re-
duce the risk of thrombosis, but simultaneously accom-
panies the increased adverse effects, such as hemorrhage,
and the financial burden. Therefore, it is always confused
to decide how long patients should take dual antiplatelet
therapy after DES implantation. In Jupiter II study, about
60% patients took clopidogrel for over 6 months. Al-
though patients in present study took clopidogrel for 4
months and then aspirin alone, no thrombosis was found
after discontinuation of clopidogrel for 126 days on av-
erage, preliminarily proving the feasibility and safety of
this antiplatelet regimen, which provides an opportunity
of receiving DES for patients who are intolerable of
long-term dual antiplatelet therapy. The relatively shorter
dual antiplatelet regimen may also associate with a de-
crease of the hemorrhage risk, adverse effects and medi-
cal expenses.
The main limitation of our study lies in that the mean
follow-up period is only 8 months, which does not reach
the designed observation time and only reflects the
mid-term clinical result. Because of the limited observa-
tion time, angiographic follow-up rate is low as well
(19%).
In conclusion, for the first time we investigated the ef-
ficacy and safety of the Janus stent, a novel DES without
polymer coating, in “real world” PCI practice in this
randomized single-center study. At our mean 8-month
follow-up, Janus stent is efficient in reducing MACE
compared with BMS, and is safe and efficient for treat-
ing AMI patients. Discontinuation of clopidogrel at
4-month after Janus implantation is safe.
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