Prospective, multi-center evaluation of a silicon carbide coated cobalt [601752]

Prospective, multi-center evaluation of a silicon carbide coated cobalt
chromium bare metal stent for percutaneous coronary interventions:Two-year results of the ENERGY Registry ☆
Raimund Erbela,⁎, Holger Eggebrechtb, Ariel Roguinc, Erwin Schroederd, Sebastian Philippe,T h o m a sH e i t z e rf,
Harald Schwackeg, Oded Ayzenbergh, Antonio Serrai, Nicolas Delarchej,
Andreas Luchnerk,T o nS l a g b o o ml, for the ENERGY Investigators
aDepartment of Cardiology, University of Duisburg-Essen, Essen, Germany
bCardioangiological Center Bethanien (CCB), Frankfurt, Germany
cDepartment of Cardiology, Rambam Medical Center, Haifa, Israel
dDivision of Cardiovascular Medicine, Cliniques Universitaires de Mont-Godinne, Yvoir, Belgium
eDepartment Internal Medicine/Cardiology, Elbe Klinikum Stade, Stade, Germany
fDepartment of Cardiology, Heart Center Dortmund, Dortmund, Germany
gDepartment of Internal Medicine, Diakonissen-Stiftungs- Krankenhaus Speyer, Germany
hThe Heart Institute, Kaplan Medical Center, Rehovot, Israel
iServicio de Cardiología, Hospital de la Santa Creu i Sant Pau, Barcelona, España
jCardiology unit, Pau General Hospital, Pau, France
kDepartment of Internal Medicine/Cardiology, Universitätsklinikum Regensburg, Germany
lDepartment of Cardiology, Onze Lieve Vrouwe Gasthuis, Amsterdam, The Netherlands
abstract article info
Article history:
Received 30 June 2014Received in revised form 24 September 2014Accepted 7 October 2014
Keywords:
Bare metal stent
Passive coatingSilicon carbideBackground: Novel bare metal stents with improved stent design may become a viable alternative to drug-eluting
stents in certain patient groups, particularly, when long-term dual antiplatelet therapy should be avoided.
Purpose: The ENERGY registry aimed to assess the safety and bene fits of a cobalt –chromium thin strut bare metal
stent with a passive coating in a large series of patients under real-world conditions.Methods and materials: This prospective registry recruited 1016 patients with 1074 lesions in 48 centers from
April to November 2010. The primary endpoint was the rate of major adverse cardiac events (MACEs), a compos-
ite of cardiac death, myocardial infarction and clinically driven target lesion revascularization.Results: More than half of the lesions (61.0%) were type A/B1 lesions, mean lesion length was 14.5 ± 6.5 mm and
mean reference vessel diameter 3.2 ± 0.5 mm. MACE rates at 6, 12 and 24 months were 4.9%, 8.1% and 9.4%, tar-
get lesion revascularization rates 2.8%, 4.9% and 5.4% and de finite stent thrombosis rates 0.5%, 0.6% and 0.6%. Sub-
groups showed signi ficant differences in baseline and procedural characteristics which did not translate into
significantly different clinical outcomes. Speci fically, MACE rates at 24 months were 13.5% in diabetics, 8.6% in
small stents and 9.6% in acute coronary syndrome patients.Conclusion: The population of ENERGY re flects real-world conditions with bare metal stents being mainly used in
simple lesions. In this setting, percutaneous coronary intervention using a cobalt –chromium thin strut bare metal
stent with a passive coating showed very good results up to 24 months. (ClinicalTrials.gov:NCT01056120)
Summary for annotated table of contents: The ENERGY international registry evaluated the safety and bene fits of a
cobalt –chromium thin strut bare metal stent with passive coating in 1016 patients under real-world conditions
until 2 years. Results were encouraging with a low composite rate of cardiac death, myocardial infarction and clin-
ically driven target lesion revascularization, even in the pre-de fined high risk groups of diabetes, stents ≤2.75 mm
and acute coronary syndrome.
© 2014 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license
(http://creativecommons.org/licenses/by-nc-nd/3.0/ ).
1. Introduction
Bare Metal Stents (BMS) were designed to address the limitations of
percutaneous transluminal coronary angioplasty (PTCA) [1],b u tw e r e
still associated with substantial restenosis rates [2–4].D r u g – e l u t i n g
stents (DES) were introduced to overcome this problem [2,4,5] ,b u tCardiovascular Revascularization Medicine 15 (2014) 381 –387
☆Disclosures: The authors have no con flict of interest to declare.
⁎Corresponding author at: Department of Cardiology, University of Duisburg-Essen,
Hufelandstraße 55, 45122 Essen, Germany. Tel.: +49 201 723 4801; fax: +49 201 723 5401.
E-mail address: erbel@uk-essen.de (R. Erbel).
http://dx.doi.org/10.1016/j.carrev.2014.10.002
1553-8389/© 2014 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license ( http://creativecommons.org/licenses/by-nc-nd/3.0/ ).
Contents lists available at ScienceDirect
Cardiovascular Revascularization Medicine

late and very late stent thrombosis of DES warranted further research
[4,6,7] . To address these limitations, several novel technologies have
been developed, one of them being BMS with an improved stent design.
Cobalt –chromium (CoCr) replaced stainless steel, allowing thinner
stent struts with the associated advantages of better flexibility and re-
duced restenosis rates [5,8,9] . In addition, passive stent coating may fur-
ther reduce restenosis rates [10,11] .
The PRO-Kinetic Energy BMS is a CoCr stent which is covered by a
thin layer of amorphous silicon carbide. In animal models, silicon car-
bide coating has been shown to reduce direct smooth-muscle-cell stim-
ulation [12] and to exhibit lower adhesion and activation of blood
platelets and leucocytes [11,13] . It was the aim of the present registry
to evaluate the clinical safety and ef ficacy of this latest generation
B M Si nal a r g e( N1000 patients) multi-center prospective observational
trial to evaluate if the preliminary promising data obtained with a small
sample size in the MULTIBENE study [14]can be replicated in daily prac-
tice and to assess outcomes in speci ficp r e – d e fined high-risk groups
such as patients with diabetes, small stents, and ACS.
2. Methods
2.1. Study design and population
The ENERGY registry was a prospective, non-randomized, multi-
center, observational registry to evaluate the clinical performance of
the PRO-Kinetic Energy BMS in a large real-world patient population
in standard clinical care. Inclusion criteria were de fined according to
the instructions for use (eligibility for percutaneous coronary interven-
tion with de novo lesions or re-stenosis after PTCA). Patients with
known allergy to anticoagulation/antiplatelet therapy and patients pre-
senting with in-stent restenosis were excluded. Additionally, the use of
more than one stent, not being a PRO-Kinetic Energy stent, within the
same vessel was discouraged, to allow to distinguish if the target vessel
events were related to the PRO-Kinetic stent or not. Clinical follow-ups
were scheduled at 6, 12 and 24 months and were performed according
to standard of care at the participating sites. The antiplatelet therapy re-
gime was also given according to standard of care at each site. Monitor-
ing included 10% source document veri fication, randomly chosen. An
independent clinical events physician reviewed and adjudicated all
suspected major adverse cardiac events, adverse device effects and seri-
ous adverse device effects.
2.2. Study device
The PRO-Kinetic Energy BMS (BIOTRONIK AG, Bülach, Switzerland)
consists of a balloon-expandable stent pre-mounted on a fast-
exchange delivery system. It is composed of CoCr L605 alloy, which is
completely covered by a thin layer of amorphous silicon carbide
(PROBIO). This layer of passive coating acts as a passive barrier, reducing
thrombogenicity and the release of potentially allergic ions [15]. The
PRO-Kinetic Energy stent is available in lengths from 9 to 40 mm and di-
ameters from 2.0 to 5.0 mm. Strut thickness is 60 μm for small stents
(2.0–3.0 mm diameter), 80 μm for medium stents (3.5 –4.0 mm diame-
ter) and 120 μmf o rl a r g es t e n t s( ≥4.5 mm diameter).
2.3. De finitions
Lesions were de fined according the AHA/ACC classi fication [16,17] .
The primary endpoint of the study was major adverse cardiac events
(MACE), a composite of cardiac death, myocardial infarction (MI), andclinically driven target lesion revascularization (TLR), at 6 months. Sec-
ondary endpoints were MACE at 12 and 24 months, and target vessel re-
vascularization (TVR), and stent thrombosis at 6, 12 and 24 months as
defined by the academic research consortium guidelines [18].2.4. Statistical analysis
Statistical analysis was performed based on available data for the
total subject cohort (intention-to-treat population) and the following
subgroups: diabetes (insulin dependent and non-insulin dependent),
stent sizes ≤2.75 mm in diameter, and ACS [19]. Continuous variables
are presented as mean ± standard deviation (SD), and compared
using the Student's t-test. Categorical variables are presented as fre-
quencies and percentages, and compared using the Fisher's Exact test
or Chi-Square test. 2-year survival was analyzed using the Kaplan –
Meier method. A p-value less than 0.05 was considered statistically sig-
nificant. For MACE, effect size between subgroups was studied using
odds ratios. All statistical analyses were carried out using SAS 9.3 (SAS
Institute Inc. Cary, NC, USA).
2.5. Role of the funding source
The study was sponsored by BIOTRONIK AG, Bülach, Switzerland.
The sponsor was involved in the design of the study, data collection,
monitoring, and data analysis and interpretation. The corresponding
author had full access to all data in the study and together with the
co-authors had final responsibility for the decision to submit
for publication.
Ethics committee approval was obtained for all participating institu-
tions and the registry was conducted in accordance with the Declaration
of Helsinki, Good Clinical Practice and ISO1455, where applicable. All
patients provided written informed consent. This study is registered at
ClinicalTrials.gov (NCT01056120).
3. Results
From April 2010 until November 2010, a total of 1016 consecutive pa-
tients with 1074 coronary lesions wer e enrolled at 48 centers in 10 coun-
tries in Europe and Israel ( Fig. 1 ). The baseline clinical characteristics are
listed in Table 1 . The mean age was 66.1 ± 12.5 years, 77.7% (n = 789)
were male, 16.5% (n = 168) had diabete s and 7.0% (n = 71) renal failure.
Several differences in baseline characteristics between the subgroups
were observed. Diabetics were signi ficantly older and had a higher inci-
dence of renal failure, hypertension, hyperlipidemia, unstable angina,
previous percutaneous co ronary intervention (PCI) and previous cerebro-
vascular attacks (CVA), but a lower rate of ACS. Patients with small stents
were older and had more diabetes and hypertension, but less were male
or had a history of smoking. Patients with ACS were younger and had a
higher incidence of smokers and a lower rate of diabetes, hypertension,
hyperlipidemia, previous coronary artery bypass grafts, MI, PCI and
CVA/transient ischemic attacks.
The majority of patients had ACC/AHA lesion classi fication B1 (n =
435, 40.5%). Lesions involving coronary bifurcations were present in
12.8% (n = 137) ( Table 2 ). The mean reference vessel diameter was
3.2 ± 0.5 mm, mean lesions length 14.5 ± 6.5 mm and mean diameter
stenosis 87.0 ± 11.7%. There were signi ficant differences in lesion and
procedural characteristics among the subgroups. Most relevant, diabetic
patients had signi ficantly more calci fication, patients with small stents
had more stents per lesion implanted and shorter lesion lengths, and
patients with ACS had less calci fication, longer lesions and higher
mean diameter stenosis.
At 6 months, two thirds (66.8%) of the patients were on dual anti-
platelet therapy (DAPT) and 7.8% received anticoagulation therapy, at
12 months, half of the patients (51.9%) received DAPT and 9.2%
anticoagulation therapy, and at 24 months 32.3% and 9.1% respectively.
At 6, 12 and 24 months, the MACE rates were 4.9%, 8.1% and 9.4%, cardi-
ac death rates 1.7%, 2.9% and 3.4%, MI rates 1.7%, 2.0% and 2.3%, TLR rates
2.8%, 4.9 and 5.4% and de finitive stent thrombosis rates 0.5%, 0.6% and
0.6%, respectively. Notably, half of the cardiac deaths were of unknown
cause (1.6% at 12 months). All-cause mortality was 4.0% at 12 months
and 4.6% at 24 months ( Fig. 2 ).382 R. Erbel et al. / Cardiovascular Revascularization Medicine 15 (2014) 381 –387

Except for cardiac death and all-cause mortality, which were signif-
icantly higher in the diabetics group (7.4% vs. 2.7% at 24 months, p =
0.007 and 8.6% vs. 3.9%, p = 0.018, respectively), there was no signi fi-
cant difference in event rates between patients with diabetes, small
stents and ACS. Respective MACE rates were 13.5%, 8.6% and 9.6% at
24 months ( Fig. 2 ) with logrank tests of 0.062, 0.658 and 0.750. In the
ACS subgroup, there was no signi ficant difference between STEMI and
NSTEMI patients (9.8% vs. 10.2%, p = 0.936), or between ACS patients
with stents ≤2.75 mm and N2.75 mm (8.1% vs. 9.7%, p = 0.638).
4. Discussion
This prospective, multi-center registry comprising N1000 all-comer
patients undergoing PCI showed that in the era of DES, BMS are mainly
used for simple lesions, as also observed in the SCAAR registry [20].I n
this setting, the use of a modern-generation thin strut BMS with passive
coating results in very good clinical outcomes with low restenosis rates
during 2-year follow-up. Even in high-risk patients (diabetics, small
vessels, or ACS) clinical outcomes were very favorable with MACE
rates of b13.5%.
The overall results were similar to other studies and registries con-
ducted with the PRO-Kinetic stent. At 6 months, clinical driven TLR
rate was 3.2% compared to 7.6% in MULTIBENE [14], 5.2% in a single cen-
ter study [21] and 4.9% in the PRO-Heal registry [11]. MACE rate was
4.9% compared to 8.7% [19]and 5.6% [11]. Further, the revascularization
rates of the ENERGY registry compared well to those of registries,randomized studies and meta-analyses of other BMS and DES. At
12 months, the revascularization rate was 4.9% versus 4.6% –17.3% for
BMS [2,4,20,22 –24]and 2.2% –10.4% for DES [2,4,20,23,25,26] .D efinite
stent thrombosis occurred in 0.6% of our patients compared to 0.3% –
1.2% in BMS as well as DES trials [2,4,20,23 –26]. Notably, the antiplatelet
regime was left to the discretion of the treating physician and the rela-
tively high rate of DAPT at follow-up might have in fluenced event rates.
Overall, the low revascularization rates support the hypothesis of a
recent analysis of 1.5 million PCI procedures from the National Cardio-
vascular Data Registry, suggesting that a less frequent use of DES in pa-
tients with a low risk of restenosis has the potential for signi ficant cost
savings while minimally increasing restenosis rates [27].S i m i l a r l y ,o u t –
comes of the SCAAR registry suggested that overall low revasculariza-
tion rates and the small absolute difference between BMS and DES donot support the use of DES in patients with a low or intermediate risk
of restenosis [28].
4.1. Subgroup analysis
This registry aimed to assess the risk pro file of pre-de fined risk
groups as treatment strategies amongst several subgroups is still un-
clear and sometimes stent design can make an eminent difference
[29]. As expected, MACE rates at follow-up were numerically higher in
the risk groups of diabetics and patients with ACS, yet the differences
were not signi ficant and outcomes were still within the range of studies
and registries with unselected patient populations.
Fig. 1. Patient status.
Table 1
Baseline characteristics.
Overall Diabetics Stents ≤2.75 mm ACS
N = 1016 N = 168 p-value N = 253 p-value N = 468 p-value
Age in years, mean ± SD 66.1 ± 12.5 68.7 ± 11.2 0.002 68.2(12.3) 0.004 63.7 ± 13.3 b0.001
Male 789(77.7) 129(76.8) 0.743 182(71.9) 0.022 368(78.6) 0.471
Diabetes 168(16.5) 168(100.0) – 56(22.1) 0.008 62(13.2) 0.008
IDDM 44(4.3) 44(26.2) – 17(6.7) 0.024 15(3.2) 0.100
Renal Failure 71(7.0) 20(11.9) 0.007 20(7.9) 0.423 28(6.0) 0.239History of smoking 636(62.6) 102(60.7) 0.528 144(56.9) 0.041 310(66.2) 0.030Hypertension 732(72.0) 156(92.9) b0.001 196(77.5) 0.032 292(62.4) b0.001
Hyperlipidemia 703(69.2) 140(83.3) b0.001 173(68.4) 0.788 288(61.5) b0.001
Indication for PCI
Stable angina 355(34.9) 63(37.5) 0.460 88(34.8) 0.887 ––
Unstable angina 140(13.8) 32(19.0) 0.029 42(16.6) 0.152 ––
ACS 468(46.1) 62(36.9) 0.008 104(41.1) 0.069 468(100.0) –
Previous CABG 60(5.9) 13(7.7) 0.272 19(7.5) 0.262 13(2.8) b0.001
Previous MI 196(19.3) 35(20.8) 0.548 52(20.6) 0.541 64(13.7) b0.001
Previous PCI 234(23.0) 53(31.5) 0.003 67(26.5) 0.119 49(10.5) b0.001
Previous CVA or TIA 45(4.4) 13(7.7) 0.023 9(3.6) 0.505 13(2.8) 0.017
Data shown as n (%) unless otherwise speci fied. ACS = acute coronary syndrome; yrs = years; IDDM = Insulin dependent diabetes mellitus; PCI = Peripheral coronary intervention;
CABG = Coronary artery bypass graft; MI = myocardial infarction; PCI = percutanous coronary intervention; CVA = cerebrovascular attack; TIA = transi ent ischemic attack.383 R. Erbel et al. / Cardiovascular Revascularization Medicine 15 (2014) 381 –387

Recently, the RESOLUTE DES received FDA approval for treatment of
coronary artery disease in diabetics. The prospectively obtained perfor-
mance goal was a composite of cardiac death, target-vessel MI and TVR
of 14.5% at 12 months in a pre-speci fied low risk cohort. In a pooled
analysis of 878 diabetics enrolled in the global RESOLUTE program this
performance goal was met with a 12-month rate of 7.8%. In the overall
diabetic group, including complex patients, the composite of cardiac
death, target-vessel MI and TLR was 11.7% for insulin-dependent dia-betics and 6.1% for non-insulin-dependent [30]. With a 11.41% compos-
ite of cardiac death, MI and TLR, and no additional TVR, the event rate of
diabetics in ENERGY hence met the performance goal for low-risk dia-
betics in RESOLUTE. Further, with a TLR rate of 5.9% and a de finite
stent thrombosis rate of 0.6%, results were similar to a prospective
study in diabetics with everolimus and paclitaxel-eluting stents whichobserved TLR in 4.2% –4.7% and stent thrombosis in 0.8% –1.3% of the
cases [ 29], and to the SCAAR registry which observed revascularization
in 5.0% of the patients treated with a BMS and 3.6% of the patients treat-
ed with a DES [28].
Similarly, a small stent respective vessel size by itself is known to
be associated with higher MACE and revascularization rates
[3,28,31] . Clinical studies showed that DES bene fit was particularly
apparent in small vessels [28,31,32] .O u rr e g i s t r y ,h o w e v e r ,s h o w e d
remarkably good outcomes in patients with small stents, which
were slightly superior to the overall ENERGY population. Further-
more, the revascularization rate of 4.1% at 12 months was lower
than published results in other cohorts treated with BMS (6.8% –
11.2%) [28,33,34] and within range of those treated with DES (3.2%
for the SCAAR registry and 4.4% for the NHLBI dynamic registry at
Fig. 2. Cumulative risks for MACE, all-cause mortality, myocardial infarction, clinically driven target lesion revascularization and de finite stent thrombosis.Table 2
Baseline lesion and procedural characteristics.
Overall Diabetics Stents ≤2.75 mm ACS
N = 1074 N = 176 p-value N = 265 p-value N = 487 p-value
Target vessel 0.147 b0.001 0.300
Right coronary artery 413(38.5) 59(33.5) 71(26.8) 200(41.1)
Left anterior descending artery 379(35.3) 60(34.1) 105(39.6) 169(34.1)
Left Circum flex artery 266(24.8) 56(31.8) 82(30.9) 110(22.6)
Ramus intermedius 10(0.9) 1(0.6) 6(2.3) 5(1.0)Unknown 6(0.6) 0(0) 1(0.4) 3(0.6)
Lesion classi fication (AHA/ACC) 0.951 0.409 b0.001
Type A 220(20.5) 38(21.6) 56(21.1) 83(17.0)Type B1 435(40.5) 72(40.9) 100(37.7) 181 (37.2)
Type B2 307(28.6) 50(28.4) 74(27.9) 151 (31.0)
Type C 108(10.1) 16(9.1) 35(13.2) 71 (6.3)Unknown 4(0.4) 0(0) 0(0) 1(0.2)
Bifurcation lesion 137(12.8) 23(13.1) 0.888 44(16.6) 0.061 69(14.2) 0.213Moderate to excessive calci fication 278(25.9) 60(34.1) 0.007 76 (28.7) 0.359 93(19.1) b0.001
Lesion length, mm ± SD 14.5 ± 6.5 14.0 ± 5.3 0.240 13.7 ± 6.1 0.013 15.7 ± 6.8 b0.001
Mean RVD, mm ± SD 3.2 ± 0.5 3.1 ± 0.5 b0.001 2.6 ± 0.2 b0.001 3.3 ± 0.5 b0.001
Mean diameter stenosis, % ± SD 87 ± 11.7 87.1 ± 10.1 0.862 86.4 ± 12.5 0.355 91.4 ± 10.0 b0.001
Stent diameter, mm ± SD 3.2 ± 0.5 3.1 ± 045 b0.001 2.6 ± 0.2 b0.001 3.2 ± 0.5 0.005
Stent length, mm ± SD 15.8 ± 4.7 15.4 ± 3.8 0.157 15.0 ± 4.2 0.001 16.6 ± 4.9 b0.001
Pre-dilatation 491(45.7) 89(50.6) 0.167 136 (51.3) 0.048 214(44.0) 0.267Post-dilatation 193(18.0) 25(14.2) 0.152 43 (16.2) 0.305 95(19.1) 0.241Number of stents per lesion, mean 1.15 1.20 0.817 1.33 0.017 1.22 0.617
D a t as h o w na sn( % )u n l e s so t h e r w i s es p e c i fied. ACS = acute coronary syndrome; AHA/ACC = American Heart Associatio n/American College of Cardiology; RVD = reference vessel diameter.384 R. Erbel et al. / Cardiovascular Revascularization Medicine 15 (2014) 381 –387

12 months and 10.3% at 9 months for the PICOLETTO study)
[28,33,35] . The most plausible explanation is that complicated
small lesions would likely have been treated with DES or left alone
originally and therefore were not included in this registry.
In a recent randomized trial in ACS, a new generation coated BMS
achieved a 12-month MACE rate which was non-inferior to an everoli-
mus eluting stent, combined with a slightly higher TLR rate and lower
definite stent thrombosis rate (9.6% vs. 9.0%, 6.5% vs. 4.9% and 0.7% vs.
2.2%) [36]. We observed similar results in our registry (8.4%, 5.0% and
0.7%), which are also in alignment with a single center study in ACS
treated with a PRO-Kinetic stent (11.1%, 2.6% and 1.8%) [37].T h e
PROMETHEUS study assessed the safety and ef ficacy of the PRO-
Kinetic stent in patients with acute ST-elevation myocardial infarction
(STEMI). At 6 months, the MACE rate was 7.8% including TLR in 6.3%
of the patients [38]compared to 6.2% and 3.0% in our registry. Favorable
clinical and angiographic outcomes were observed in large ( N3.0 mm)arteries, but not in small ones. We, however, observed favorable results
in patients with STEMI and small stents ≤2.75 mm too, with a MACE
rate of 6.0% and a TLR rate of 2.1%.
4.2. Limitations
The registry was non-randomized and therefore a direct comparison
to other coronary stents is not possible. Lesions were mostly not com-
plex, most likely re flecting the daily clinical practice, using BMS only
in a selected group of patients and lesions. Thus, a comparison to DES
is hampered and biased as the more complex lesions, e.g. small vessels
and long lesions, are rather treated with DES than with BMS. Further-
more, there was an unusually long duration of DAPT which is unex-
plained and which potentially has biased the results. Angiographic
assessments are missing as treatment was according to standard of
care. Especially under the light of low revascularization rates,
Fig. 2 (continued ).385 R. Erbel et al. / Cardiovascular Revascularization Medicine 15 (2014) 381 –387

parameters like binary restenosis rate and late lumen loss would have
been of interest. The average recruitment rate was low, which might
be due to a less frequent use of BMS in some centers and due to a
short enrollment period in others. However, as in other studies and reg-
istries, a non-consecutive enrollment cannot be ruled out. When
assessing the 2-year data, it has to be considered that follow-up is
only available for 90% of the patients. Furthermore, the small sample
size in the subgroups does not allow generalizing the results to popula-
tions with diabetes, small stents, and ACS, but can only be regarded as
hypothesis generating.
5. Conclusions
The population of ENERGY re flects real-world conditions with bare
metal stents being mainly used in simple lesions. In this setting a BMS
with very thin struts and passive coating demonstrates very goodshort and long term results, even in subgroups with small stents and
ACS, and acceptable results in diabetics. Utility of such modern BMS
platforms in selected groups of patients and lesions is still relevant in
the era of DES.
Acknowledgments
The study was supported by BIOTRONIK AG, Bülach, Switzerland.
We are grateful for data review by the clinical events physician,
Dr. Ralf Birkemeyer, and we thank Dr. Beatrix Dörr, Clinical Research
Consultant, for her help in preparing the draft manuscript.
References
[1]Erbel R, Schatz R, Dietz U, Nixdorrf U, Haude M, Aichinger S, et al. Balloon dilatation
and coronary vascular stent implantation. Z Kardiol 1989;78(2):71 –7.
Fig. 2 (continued ).386 R. Erbel et al. / Cardiovascular Revascularization Medicine 15 (2014) 381 –387

[2]Stone GW, Ellis SG, Colombo A, Dawkins KD, Grube E, Cutlip DE, et al. Offsetting im-
pact of thrombosis and restenosis on the occurrence of death and myocardial infarc-
tion after paclitaxel-eluting and bare metal stent implantation. Circulation 2007;115
(22):2842 –7.
[3]Kastrati A, Mehilli J, Dirschinger J, Pache J, Ulm K, Schühlen H, et al. Restenosis after
coronary placement of various stent types. Am J Cardiol 2001;87(1):34 –9.
[4]Stettler C, Wandel S, Allemann S, Kastrati A, Morice MC, Schömig A, et al. Outcomes
associated with drug-eluting and bare-metal stents: a collaborative network meta-
analysis. Lancet 2007;370:937 –48.
[5]Doostzadeh J, Clark LN, Bezenek S, Pierson W, Sood PR, Sudhir K. Recent progress in
percutaneous coronary intervention: evolution of the drug-eluting stents, focus onthe XIENCE V drug-eluting stent. Coron Artery Dis 2010;21(1):46 –56.
[6]Lagerqvist B, James SK, Stenestrand U, Lindbäck J, Nilsson T, Wallentin L. Long-term
outcomes with drug-eluting stents versus bare-metal stents in Sweden. N Engl J
Med 2007;356(10):1009 –19.
[7]Pfisterer M, Brunner-La Rocca HP, Buser PT, et al. Late clinical events after clopidogrel
discontinuation may limit the bene fit of drug-eluting stents: an observational study
of drug-eluting versus bare-metal stents. J Am Coll Cardiol 2006;48(12):2584 –91.
[8]Menown IB, Noad R, Garcia EJ, Meredith I. The platinum chromium element stent
platform: from alloy, to design, to clinical practice. Adv Ther 2010;27:129 –41.
[9]Kastrati A, Mehilli J, Dirschinger J, Dotzer F, Schühlen H, Neumann FJ, et al.
Intracoronary stenting and angiographic results. Strut thickness effect on restenosis
outcome (ISAR-STEREO) trial. Circulation 2001;103:2816 –21.
[10] Elbaz M, El Mokhtar E, Fourcade J, Mourali S, Hobeika R, Carrié D, et al. Does stent
design affect the long-term outcome after coronary stenting? Catheter Cardiovasc
Interv 2002;56:305 –11.
[11] Dahm JB, Willems T, Wolpers HG, Nordbeck H, Becker J, Ruppert J. Clinical investiga-
tion into the observation that silicon carbide coating on cobalt chromium stents
leads to early differentiating functional endothelial layer, increased safety and
DES-like recurrent stenosis rates: results of the PRO-Heal Registry (PRO-Kinetic en-hancing rapid in-stent endothelialisation). EuroIntervention 2009;4:502 –8.
[12] Stoll H, Scheller B. A potential „In Stent Restenosis Model “Evaluating the Kinetics of
Smooth Muscle Cell Proliferation on Metallic Surfaces in Vitro. Prog Biomed Res
2001;6:202 –7.
[13] Unverdorben M, Sattler K, Degenhardt R, Fries R, Abt B, Wagner E, et al. Comparison
of a silicon carbide coated stent versus a noncoated stent in humans: the Tenax- ver-
sus Nir-Stent Study (TENISS). J Interv Cardiol 2003;16(4):325 –33.
[14] Vermeersch P, Appelmann Y, Horstkotte D, Richart G, Boland J, Lalmand J, et al. Safe-
ty and Ef ficacy of the cobalt chromium PRO-Kinetik coronary stent system: results of
the MULTIBENE study. Cardiovasc Revasc Med 2012;13(6):316 –20.
[15] Schmehl JM, Harder C, Wendel HP, Claussen CD, Tepe G. Silicon carbide coating of
nitinol stents to increase antithrombogenic properties and reduce nickel release.
Cardiovasc Revasc Med 2008;9(4):255 –62.
[16] Ryan TJ, Faxon DP, Gunnar RM, Kennedy JW, King III SB, Loop FD, et al. Guidelines for
percutaneous transluminal coronary angioplasty: a report of the American College of
Cardiology/American Heart Association Task Force on Assessment of Diagnostic and
Therapeutic Cardiovascular Procedures (Subcommittee on Percutaneous Translumi-nal Coronary Angioplasty). J Am Coll Cardiol 1988;12:529 –45.
[17]
Ellis SG, Vandormael MG, Cowley MJ, DiSciascio G, Deligonul U, Topol EJ, et al. Cor-
onary morphologic and clinical determinants of procedural outcome with angioplas-
ty for multivessel coronary disease: implications for patient selection. Circulation
1990;82:1193 –202.
[18] Cutlip DE, Windecker S, Mehran R, Boam A, Cohen DJ, van Es GA, et al. Academic Re-
search Consortium. Clinical end points in coronary stent trials: a case for standard-
ized de finitions. Circulation 2007;115:2344 –51.
[19] Task Force for Diagnosis and Treatment of Non-ST-Segment Elevation Acute Coro-
nary Syndromes of European Society of CardiologyBassand JP, Hamm CW,
Ardissino D, Boersma E, Budaj A, Fernández-Avilés F, et al. Guidelines for the diagno-
sis and treatment of non-ST-segment elevation acute coronary syndromes. EurHeart J 2007;28:1598 –660.
[20] Sarno G, Lagerqvist B, Fröbert O, Nilsson J, Olivecrona G, Omerovic E, et al. Lower risk
of stent thrombosis and restenosis with unrestricted use of 'new-generation' drug-
eluting stents: a report from the nationwide Swedish Coronary Angiography and
Angioplasty Registry (SCAAR). Eur Heart J 2012;33(5):606 –13.[21] Kornowski R, Vaknin-Assa H, Ukabi S, Lev EI, Assali A. PRO-Kinetic: results from an
"all-comers" single centre clinical experience. EuroIntervention 2009;5:109 –14.
[22] Abdel-Wahab M, Toelg R, Kassner G, Klatt L, Sherif MA, Geist V, et al. Long-term
clinical outcome of thin-strut cobalt –chromium stents in the drug-eluting stent
era: results of the COBALT (comparison of bare-metal stents in all-comers' lesion
treatment) registry. J Interv Cardiol 2011;24:496 –504.
[23] Nienaber CA, Akin I, Schneider S, Senges J, Fetsch T, Tebbe U, et al. Clinical outcomes
after sirolimus-eluting, paclitaxel-eluting, and bare metal stents (from the first
phase of the prospective multicenter German DES.DE Registry). Am J Cardiol 2009;
104:1362 –9.
[24] Angioi M, Barragan P, Cattan S, Collet F, Dupouy P, Durand P, et al. French Ministry of
Health prospective multicentre study using bio-active stents coated with titanium
nitride oxide: the EVIDENCE registry. Arch Cardiovasc Dis 2012;105(2):60 –7.
[25] Serruys PW, Silber S, Garg S, van Geuns RJ, Richardt G, Buszman PE, et al. Compari-
son of zotarolimus-eluting and everolimus-eluting coronary stents. N Engl J Med
2010;363(2):136 –46.
[26] Stone GW, Teirstein PS, Meredith IT, Farah B, Dubois CL, Feldman RL, et al. PLATI-
NUM Trial Investigators. A prospective, randomized evaluation of a noveleverolimus-eluting coronary stent: the PLATINUM (a Prospective, Randomized,
Multicenter Trial to Assess an Everolimus-Eluting Coronary Stent System [PROMUS
Element] for the Treatment of Up to Two de Novo Coronary Artery Lesions) trial.
J Am Coll Cardiol 2011;57(16):1700 –8.
[27] Amin AP, Spertus JA, Cohen DJ, Chhatriwalla A, Kennedy KF, Vilain K, et al. Use of
drug-eluting stents as a function of predicted bene fit: clinical and economic implica-
tions of current practice. Arch Intern Med 2012;172(15):1145 –52.
[28] James SK, Stenestrand U, Lindbäck J, Carlsson J, Scherstén F, Nilsson T, et al. Long-
term safety and ef ficacy of drug-eluting versus bare-metal stents in Sweden. N
Engl J Med 2009;360(19):1933 –45.
[29] Kereiakes DJ, Cutlip DE, Applegate RJ, Wang J, Yaqub M, Sood P, et al. Outcomes in
diabetic and nondiabetic patients treated with everolimus- or paclitaxel-elutingstents: results from the SPIRIT IV clinical trial (Clinical Evaluation of the XIENCE V
Everolimus Eluting Coronary Stent System). J Am Coll Cardiol 2010;56(25):2084 –9.
[30] Silber S, Serruys PW, Leon MB, Meredith IT, Windecker S, Neumann FJ, et al. Clinical
outcome of patients with and without diabetes mellitus after percutaneous coronary
intervention with the resolute zotarolimus-eluting stent: 2-year results from theprospectively pooled analysis of the international global RESOLUTE program. JACC
Cardiovasc Interv 2013;6(4):357 –68.
[31]
Pfisterer M, Brunner-La Rocca HP, Rickenbacher P, Hunziker P, Mueller C. Long-term
benefit-risk balance of drug-eluting vs. bare-metal stents in daily practice: does
stent diameter matter? Three-year follow-up of BASKET. Eur Heart J 2009;30:16 –24.
[32] Daemen J, Simoons ML, Wijns W, Bagust A, Bos G, Bowen JM, et al. Meeting Report
ESC Forum on Drug Eluting Stents European Heart House, Nice, 27-28 September
2007. Eur Heart J 2009;30:152 –61.
[33] Parikh SV, Luna M, Selzer F, Marroquin OC, Mulukutla SR, Abbott JD, et al. Outcomes
of small coronary artery stenting with bare-metal stents vs. drug-eluting stents: re-
sults from the NHLBI dynamic registry. Catheter Cardiovasc Interv 2011. http://dx.
doi.org/10.1002/ccd.23194 [Epub ahead of print].
[34] Haude M, Konorza TF, Kalnins U, Erglis A, Saunamäki K, Glogar HD, et al. Heparin-
COAted STents in small coronary arteries Trial Investigators. Heparin-coated stent
placement for the treatment of stenoses in small coronary arteries of symptomatic
patients. Circulation 2003;107(9):1265 –70.
[35] Cortese B, Micheli A, Picchi A, Coppolaro A, Bandinelli L, Severi S, et al. Paclitaxel-
coated balloon versus drug-eluting stent during PCI of small coronary vessels, a pro-
spective randomised clinical trial. The PICCOLETO study. Heart 2010;96(16):1291 –6.
[36] Karjalainen PP, Niemelä M, Airaksinen JK, Rivero-Crespo F, Romppanen H, Sia J, et al.
A prospective randomised comparison of titanium-nitride-oxide-coated bioactive
stents with everolimus-eluting stents in acute coronary syndrome: the BASE-ACS
trial. EuroIntervention 2012;8(3):306 –15.
[37] Berlin T, Rozenbaum E, Arbel J, Reges O, Erel J, Shetboun I, et al. Six- and twelve-
month clinical outcomes after implantation of prokinetic BMS in patients with
acute coronary syndrome. J Interv Cardiol 2010;23(4):377 –81.
[38] Lim SY, Park HW, Chung WY, Kim SY, Kim KS, Bae JW, et al. The Ef ficacy and Safety of
PRO-Kinetic Metal Alloy Stent in Hospitalized Patients with Acute ST-Elevation Myo-
cardial Infarction (The PROMETHEUS Study). J Invasive Cardiol 2012;24(6):270 –3.387 R. Erbel et al. / Cardiovascular Revascularization Medicine 15 (2014) 381 –387