The cumulative frequency of the percentage of stenosis diameter at baseline,
immediately after stent implantation, and after 8 months for patients receiving
a sirolimus-eluting stent (solid lines) or an uncoated stent (dashed lines).
Dotted line indicates threshold for restenosis.
CI indicates confidence interval; LAD, left anterior descending. The
size of the data markers is proportional to the number of patients.
*Median unbiased exact odds ratio.
Ardissino D, Cavallini C, Bramucci E, Indolfi C, Marzocchi A, Manari A, Angeloni G, Carosio G, Bonizzoni E, Colusso S, Repetto M, Merlini PA, SES-SMART Investigators FT. Sirolimus-Eluting vs Uncoated Stents for Prevention of Restenosis in Small Coronary ArteriesA Randomized Trial. JAMA. 2004;292(22):2727-2734. doi:10.1001/jama.292.22.2727
Author Affiliations: Division of Cardiology,
Ospedale Maggiore, University of Parma (Dr Ardissino); Division of Cardiology,
Ospedale Ca’ Foncello, Treviso (Dr Cavallini); Division of Cardiology,
Policlinico San Matteo, Istituto di Ricovero e Cura a Carattere Scientifico,
University of Pavia (Dr Bramucci); Division of Cardiology, University of Magna
Grecia, Catanzaro (Dr Indolfi); Division of Cardiology, Ospedale Sant’Orsola,
University of Bologna (Dr Marzocchi); Division of Cardiology, Ospedale Santa
Maria Nuova, Reggio Emilia (Dr Manari); Division of Cardiology, Policlinico
A. Gemelli, University of Sacro Cuore, Rome (Dr Angeloni); Division of Cardiology,
Ospedale SS Antonio e Biagio e Cesare Arrigo, Alessandria (Dr Carosio); Mediolanum
Cardio Research (Mss Colusso and Repetto); Institute of Medical Statistics
and Biometry, University of Milan (Dr Bonizzoni); and Division of Cardiology,
Ospedale Niguarda, Milan (Dr Merlini), Italy.
Context Percutaneous coronary revascularization of small vessels is associated
with a high restenosis rate. Sirolimus-eluting stents reduce restenosis in
simple and previously untreated lesions of large coronary arteries, but their
outcomes in small vessels have not been adequately investigated.
Objective To determine whether sirolimus-eluting stents are associated with a
reduced 8-month rate of angiographic restenosis in comparison with an uncoated
Design, Setting, and Patients This was a randomized, multicenter, single-blind, prospective trial
performed with 257 patients undergoing percutaneous coronary revascularization
for ischemic heart disease, and who had a previously untreated atherosclerotic
lesion located in a small segment with a diameter of 2.75 mm or less, in 20
Italian centers between August 2002 and December 2003.
Intervention Patients were randomly assigned to receive a sirolimus-eluting stent
(129 patients) or an uncoated stent having an identical architecture and radiographic
appearance (128 patients).
Main Outcome Measures The primary end point was the 8-month binary in-segment restenosis rate;
secondary end points included procedural success and the 8-month rate of major
adverse cardiac and cerebrovascular events.
Results The mean (SD) reference diameter of the treated segment was 2.2 (0.28)
mm; the lesion length, 11.84 (6.15) mm. After 8 months, the binary in-segment
restenosis rate was 53.1% (60/113) in the patients receiving an uncoated stent
and 9.8% (12/123) in those receiving a sirolimus-eluting stent (relative risk
[RR], 0.18; 95% confidence interval [CI], 0.10-0.32; P<.001).
Fewer patients randomized to sirolimus-eluting stents experienced major adverse
cardiac events (12/129 [9.3%] vs 40/128 [31.3%]; RR, 0.30; 95% CI, 0.15-0.55; P<.001) mainly because of a reduction in target lesion
revascularization (9/129 [7%] vs 27/128 [21.1%]; RR, 0.33; 95% CI, 0.14-0.70; P = .002) and myocardial infarction (2/129 [1.6%]
vs 10/129 [7.8%]; RR, 0.20; 95% CI, 0.01-0.93; P = .04).
Conclusion The use of sirolimus-eluting stents to treat atherosclerotic lesions
in small coronary arteries reduces restenosis and may also reduce major adverse
Atherosclerotic lesions of small coronary arteries are frequently found
in patients undergoing revascularization.1- 5 However,
the revascularization of small coronary arteries is a problem for bypass surgery
because it is technically difficult and associated with a high failure and
mortality rate6,7 and for percutaneous
coronary revascularization because it is associated with high rates of acute
complications and restenosis after standard balloon angioplasty1- 3 and
It has been shown that sirolimus-eluting stents reduce angiographic
restenosis and improve the rate of event-free survival in patients who have
coronary artery disease and are at low risk of restenosis.8 More
recent reports have also shown the efficacy of drug-eluting stents under more
challenging conditions such as long and complex lesions, and post hoc analyses
of trial subpopulations suggest that drug-eluting stents may also effectively
prevent restenosis in small vessels.9- 11
This randomized, multicenter, prospective trial was designed to test
the hypothesis that the implantation of a sirolimus-eluting stent in small
coronary arteries is associated with a reduced 8-month rate of angiographic
restenosis in comparison with the implantation of an uncoated stent having
an identical architecture.
Eligible patients had to be aged 18 years or older, with a documented
diagnosis of acute coronary syndrome (without persistent ST-segment elevation),
stable angina pectoris, or silent myocardial ischemia as shown by exercise
stress test. Additional eligibility criteria were the presence of a single,
previously untreated 50% to 99% target lesion in a native coronary artery
2.75 mm in diameter or less, which could be completely covered by a single
stent (maximum length, 33 mm). The patients could have had single-vessel or
multivessel disease but, in the latter case, had to have the nonrandomized
lesion located in other coronary vessels.
Major exclusion criteria were recent ST-segment elevation acute coronary
syndrome (within the previous 15 days), severe calcifications or thrombus-containing
lesions, a left ventricular ejection fraction less than 30%, and known allergies
to aspirin, clopidogrel, ticlopidine, heparin, stainless steel, contrast agents,
or sirolimus. The study protocol was approved by the ethics committee of each
participating center, and all patients gave written informed consent.
Online quantitative coronary angiography confirming vessel diameter
and lesion-length enrollment criteria was performed before randomization.
An automated telephone randomization system was used to assign the patients
to treatment with a sirolimus-eluting stent (Cypher balloon-expandable stent;
Cordis, Miami Lakes, Fla) or an uncoated stent of identical architecture and
radiographic appearance (Bx Sonic balloon-expandable stent; Cordis), in a
1:1 ratio according to a centralized list. The randomization list was generated
for a completely randomized design, ie, without blocks or stratification factors,
using the SAS PLAN (SAS Institute Inc, Cary, NC) procedure. The investigators
had to digitize patient date of birth, site number, vessel size, and stent
length by means of an interactive voice recording system to obtain the assigned
treatment. Data were confirmed by fax, which was included in the case report
Diameters of both types of stents were 2.25, 2.50, and 2.75 mm, and
lengths were 8, 13, 18, 23, 28, and 33 mm. The 2 types of stents were visually
and angiographically indistinguishable. The lesions were treated by using
standard interventional techniques, including mandatory balloon dilatation
before stent placement.
Before the index procedure, all patients received oral aspirin once
daily and clopidogrel (a loading dose of 300 mg at least 2 hours before the
procedure). Patients who had been pretreated with ticlopidine (250 mg twice
a day) or clopidogrel (75 mg once daily) for at least 72 hours did not receive
a clopidogrel loading dose. During the procedure, heparin was given as a bolus
at 70 U/kg, with additional boluses to maintain an activated clotting time
of more than 250 seconds. The use of glycoprotein IIb/IIIa inhibitors was
encouraged but left to the discretion of the attending physician. Heparin
administration was discontinued immediately after the procedure.
A 12-lead electrocardiogram was obtained before the procedure, immediately
afterward, and 24 hours later or at discharge if earlier. Cardiac enzymes
creatine kinase (CK) and CK-MB were evaluated twice within 8 to 16 and 18
to 24 hours of the procedure or at hospital discharge if earlier. Discharged
patients received a regimen of aspirin (100 mg once daily indefinitely) and
clopidogrel (75 mg once daily for at least 2 months). All patients were clinically
followed up after 1 and 8 months by the trial coordinator at each site. Follow-up
coronary angiography was performed after a mean (SD) of 8 (0.5) months.
Coronary angiograms obtained at baseline, on completion of the stenting
procedure, and after 8 months were analyzed with a computer-based algorithm
developed by MEDIS (version 5.1) (MEDIS, Medical Imaging System, Leiden, the
Netherlands). The projection that best showed the stenosis in its tightest
view was used for all angiograms; all details of the angiographic procedure
were recorded in the case report forms. For standardization, each angiogram
sequence was preceded by an intracoronary injection of 200 μg of nitroglycerin.
Quantitative angiographic analyses were performed by 1 experienced cardiologist
who was blinded to the patient’s identity, type of stent used, outcome,
and film sequence. The minimal luminal diameter (MLD) and the nearest normal
reference diameter (RVD) were measured in millimeters by using the catheter
as a scaling factor. Percentage of stenosis was calculated as 100 (1 −
MLD/RVD). Binary restenosis was defined as a stenosis of more than 50% of
the MLD in the target lesion at angiographic follow-up. Acute gain was defined
as the difference between the MLD after stent implantation and baseline MLD.
Late luminal loss was defined as the difference between the MLD at the end
of the stenting procedure and that measured during follow-up. The late loss
index was defined as late loss divided by acute gain. Quantitative angiographic
measurements of the target lesion were obtained in the “in-stent”
zone (including only the stent segment) and in the “in-segment”
zone (including the stented segment and the 5-mm margins proximal and distal
to the stent); intraobserver and interobserver variabilities of the quantitative
assessments have been previously reported.12
The primary end point of the study was the 8-month angiographic binary
in-segment restenosis rate. Secondary end points were procedural success,
8-month in-segment MLD, late luminal loss, late loss index, and major adverse
cardiac and cerebrovascular events. Procedural success was defined as the
achievement of a residual in-stent stenosis of less than 30% associated with
thrombolysis in myocardial infarction 3 flow, in the absence of a dissection
of more than D1, a grade according to the National Heart, Lung, and Blood
Institute classification, without the occurrence of death, myocardial infarction,
or repeated target lesion revascularization during hospitalization. Major
adverse cardiac and cerebrovascular events were defined as cardiac death,
myocardial infarction (Q wave and non–Q wave), cerebrovascular accident,
emergency or elective coronary artery bypass grafting, or emergency or elective
repeated percutaneous transluminal coronary intervention of the target lesion.
All deaths were considered cardiac unless an unequivocal noncardiac cause
could be established. Q-wave myocardial infarction was defined as the occurrence
of prolonged chest pain with an increase in the CK-MB fraction of more than
3 times the upper normal limit and the development of new abnormal Q waves:
non–Q-wave myocardial infarction was defined as the absence of the latter.
Target lesion revascularization was defined as repeated emergency or elective
percutaneous transluminal coronary intervention or emergency or elective coronary
artery bypass grafting performed because of restenosis of the target lesion
in association with angina, objective evidence of myocardial ischemia, or
both. A cerebrovascular accident was defined as the sudden onset of vertigo,
numbness, aphasia, or dysarthria persisting for more than 24 hours.
Stent thrombosis was defined as an angiographic thrombus within the
stented vessel at a clinically driven angiographic restudy for documented
All major adverse cardiac and cerebrovascular events and stent thrombosis
were determined for the in-hospital period, from hospital discharge up to
8 months, and cumulatively for all of the 8-month follow-up period; they were
assessed by an independent clinical events committee unaware of treatment
On the basis of the available data concerning the restenosis rate in
small arteries, it was calculated that the sample size required to demonstrate
a 66% reduction in restenosis (from 30% to 10%) by means of a 2-sided test
with an α error of .05 and a β error of .10 was 103 patients per
group. To compensate for unsuccessful interventions and losses to follow-up,
the sample size was increased by 25% to 128 patients per group.
The continuous variables were compared between groups by using the t test. Categorical variables were compared using the χ2 test. The binary study end points were analyzed using the Fisher exact
test; the relative risks or odds ratios and their 95% confidence intervals
(CIs) are also reported. All of the statistical analyses were performed using
SAS software (version 6.12; SAS Institute) on the basis of the intention-to-treat
principle, ie, the primary analysis included all of the patients randomized
to 1 of the 2 treatments and for whom follow-up coronary angiography was available,
regardless of treatment actually received. Because of some imbalances in baseline
characteristics, the main study results were confirmed by means of stratified
analyses and by multivariable logistic regression analysis. Differences were
considered statistically significant at P<.05
The trial profile is shown in Figure 1.
Between August 2002 and February 2003, 260 patients were enrolled in
20 Italian centers. Three patients were not randomized because of the discovery
of exclusion criteria that became apparent only after enrollment. The final
patient cohort therefore included 257 patients: 129 in the sirolimus-eluting
stent group and 128 in the uncoated stent group.
Characteristics of the patients, lesions, and procedures are reported
in Table 1 and Table 2. The groups were generally well matched in terms of patient
and lesion characteristics; however, the patients treated with sirolimus-eluting
stents had longer target lesions and therefore received longer stents. Procedural
success rates were excellent (>95%) and similar in both groups. The patients
in both groups had small vessels, with a mean reference diameter of only 2.2
(SD, 0.28) mm.
Minimal luminal diameter and percentage of stenosis diameter at baseline
and after stent implantation were similar in the 2 groups (Table 3). Follow-up angiographic data were available for 123 patients
treated with sirolimus-eluting stents (95.3%) and 113 of those receiving uncoated
stents (88.3%). After 8 months, the MLD, percentage of the stenosis diameter,
late luminal loss, and the late loss index in the in-segment and in-stent
zones improved more in the sirolimus-eluting stent group (P<.001 for all comparisons). The frequency of binary in-segment
restenosis was 9.8% in the patients receiving sirolimus-eluting stents and
53.1% in those receiving uncoated stents (relative risk, 0.18; 95% CI, 0.10-0.32; P<.001); the frequency of binary in-stent restenosis
was 4.9% and 49.1%, respectively (relative risk, 0.10; 95% CI, 0.04-0.22; P<.001). Cumulative frequency curves of in-segment percentage
of the diameter of stenosis at baseline, after stent implantation, and at
8 months of follow-up are shown in Figure 2.
In stratified analyses, the reduction of risk of restenosis with the sirolimus-eluting
stent in comparison with the uncoated stent was independent of sex, diabetes
mellitus status, clinical presentation (acute coronary syndrome vs chronic
stable angina or silent myocardial ischemia), epicardial vessel location,
stent diameter, and stent length (Figure 3).
Similarly, in a multivariable logistic regression model, treatment with a
sirolimus-eluting stent was associated with a markedly lower rate of restenosis
(adjusted odds ratio, 0.11; 95% CI, 0.05-0.24; P<.001).
The major in-hospital, out-of-hospital, and cumulative 8-month adverse
cardiac and cerebrovascular event rates are listed in Table 4. There were 2 deaths in the uncoated stent group (one caused
by pneumonia and the other by stroke followed by pneumonia) and none in the
sirolimus stent group. The cumulative frequency of myocardial infarction was
lower in the sirolimus stent group (relative risk, 0.20; 95% CI, 0.01-0.93; P = .04). Target lesion revascularization was
performed less frequently in the patients receiving sirolimus-eluting stents
(relative risk, 0.33; 95% CI, 0.14-0.70; P = .002).
Major adverse cardiac and cerebrovascular events were less frequently observed
in the sirolimus stent group (relative risk, 0.30; 95% CI, 0.15-0.55; P<.001). Stent thrombosis was infrequent and occurred
in 2 patients during hospital stay, 1 in the sirolimus stent group and 1 in
the uncoated stent group; out-of-hospital stent thrombosis occurred in 3 of
the patients receiving the uncoated stents and in none of the sirolimus stent
group (relative risk, 0.26; 95% CI, 0.1-2.3). One of the non–Q-wave
myocardial infarctions that occurred during hospitalization in the sirolimus
stent group was clearly unrelated to the target lesion, as was the related
Percutaneous coronary revascularization by means of balloon angioplasty
has a lower primary success rate and a higher restenosis rate in small coronary
arteries than in large vessels.1- 3 Restenosis
in small coronary arteries may be as high as 50%, as an inverse relationship
between vessel size and angiographic restenosis has reported.4,5 Stenting
has become the major means of percutaneous coronary revascularization because
it has been demonstrated to be superior to balloon angioplasty in preventing
restenosis of new focal lesions in large coronary arteries,13,14 but
conflicting results have been reported about efficacy in small vessels.15- 20 Potential
explanations for the lack of efficacy of coronary angioplasty with or without
stent implantation in preventing restenosis in small vessels may be related
to characteristics of patients harboring atherosclerotic small-vessel lesions,
ie, women, diabetic patients, the elderly, and patients with peripheral vascular
disease, all of whom are associated with a higher risk of restenosis.21,22 Another possible explanation may
be related to the narrow diameter of the vessels, which cannot accommodate
even minimal neointimal hyperplasia after angioplasty or stent deployment
without becoming restenotic.
Given their ability to deliver prolonged and sufficient intramural drug
concentrations to target coronary segments, drug-eluting stents are able to
dramatically reduce neointimal hyperplasia,23,24 and
this specific mechanism may be particularly useful in reducing restenosis
in small coronary arteries.
The results of the present study demonstrate that the implantation of
a sirolimus-eluting stent to treat atherosclerotic lesions of small coronary
arteries is safe, effective, and associated with a lower incidence of angiographic
restenosis in comparison with an uncoated stent. Because the 2 stents had
an identical architecture, the only difference between them was the release
of sirolimus, which reduced the rate of angiographic restenosis from 53.1%
to 9.8%, with a relative risk reduction of 82%. The high restenosis rate observed
in the uncoated stent group may partially account for the high absolute and
relative risk reduction; however, this rate of restenosis is not all that
surprising, given the high-risk population and high-risk lesions treated.
Nevertheless, the 9.8% restenosis rate in the sirolimus-eluting stent group
is also remarkably low. Previous post hoc analyses of the effect of overlapping
sirolimus-eluting stents in small vessels revealed less satisfactory results
(18.4% of restenosis in vessels with an average diameter of 2.32 mm).9 The use of adequately sized single stents that were
almost 60% longer than the lesion may explain the remarkably low restenosis
Not only was there a reduction in the risk of angiographic restenosis
but also a lower rate of major adverse cardiovascular events, mainly because
of the decreased incidence of ischemia-driven target-lesion revascularization
and myocardial infarction. Why the implantation of a sirolimus-eluting stent
may prevent the development of myocardial infarction remains unclear and needs
to be confirmed. The beneficial effects of the sirolimus-eluting stent were
achieved without any increase in complications, including stent thrombosis,
which is a feared event, particularly in patients receiving stents in small
This was a single-blind, randomized trial, and therefore the cardiologists
performing the procedure knew whether the patients were receiving a drug-eluting
or an uncoated stent. However, the risk of a selection bias was minimized
by the completely randomized design. Furthermore, because patients and the
angiographic core laboratory personnel were blinded to the assigned treatment,
symptom reporting and the angiographic results should not have been influenced
by the open-label design.
Another possible limitation is related to the comparator bare-metal
stent used. A different comparator with thinner struts might have led to a
lower incidence of restenosis in the uncoated stent group. However, our purpose
was to compare 2 angiographically indistinguishable stents with the same architecture
to verify the effect of the eluting drug.
Despite these limitations, we found that in a highly challenging condition,
namely, revascularization of small coronary arteries in patients with stable
angina pectoris or acute coronary syndrome without ST-segment elevation, the
use of sirolimus-eluting stents likely represents an advance in the prevention
of angiographic restenosis and the short-term recurrence of adverse cardiac
events. To establish their long-term efficacy and cost-effectiveness in the
treatment of small coronary arteries, extended follow-up is required.
Corresponding Author: Diego Ardissino, MD,
Dipartimento del Cuore, Divisione di Cardiologia, Ospedale Maggiore di Parma,
Università degli Studi di Parma, Via Gramsci 14, 43100 Parma, Italy
Author Contributions: Dr Ardissinio had full
access to all of the data in the study and takes responsibility for the integrity
of the data and the accuracy of the data analysis.
Study concept and design: Ardissino, Cavallini,
Acquisition of data: Ardissino, Bramucci, Indolfi,
Marzocchi, Manari, Angeloni, Carosio, Repetto, Merlini.
Analysis and interpretation of data: Ardissino,
Cavallini, Bonizzoni, Repetto, Merlini.
Drafting of the manuscript: Ardissino, Cavallini,
Bonizzoni, Marzocchi, Colusso, Merlini.
Critical revision of the manuscript for important
intellectual content: Ardissino, Bramucci, Indolfi, Manari, Angeloni,
Carosio, Bonizzoni, Merlini.
Statistical analysis: Ardissino, Bonizzoni,
Obtained funding: Ardissino.
Administrative, technical, or material support:
Study supervision: Ardissino.
Investigators and Institutions in the Sirolimus-Eluting
Stent in the Prevention of Restenosis in Small Coronary Arteries (the SES-SMART
Chairmen: Diego Ardissino, MD, Ospedale Maggiore
di Parma, Universita’ degli Studi di Parma, Parma; Claudio Cavallini,
MD, Ospedale Ca’ Foncello, Treviso.
Executive Committee: Ezio Bramucci, MD, Policlinico
San Matteo, Universita’ degli Studi di Pavia, Pavia; Ciro Indolfi, MD,
Universita’ degli Studi della Magna Grecia, Catanzaro; Antonio Marzocchi,
MD, Policlinico Sant’Orsola, Universita’ degli Studi di Bologna,
Bologna; Nello Becco, Cordis Italia, Milano.
Steering Committee: Antonio Manari, MD, Ospedale
S. Maria Nuova, Reggio Emilia; Giulia Angeloni, MD, Università Cattolica
Sacro Cuore di Roma, Policlinico A. Gemelli, Roma; Giuseppe Carosio, MD, Azienda
Ospedaliera SS Antonio e Biagio e Cesare Arrigo, Alessandria; Enrico Aurier,
MD, Ospedale Maggiore di Parma, Universita’ degli Studi di Parma, Parma;
Luigi Piatti, MD, Ospedale A. Manzoni, Lecco; Roberto Violini, MD, Azienda
Ospedaliera S. Camillo Forlanini, Roma; Pasquale Lisanti, MD, Azienda Ospedaliera
S. Carlo, Potenza; Mauro De Benedictis, MD, Ospedale Mauriziano Umberto I,
Torino; Giancarlo Piovaccari, MD, Ospedale Infermi, Rimini; Arturo Bande,
MD, Azienda Ospedaliera G. Brotzu, Cagliari; Carmelo Cernigliaro, MD, Unità
Operativa di Cardiologia Novara, Novara; Zoran Olivari, MD, Ospedale Cà
Foncello, Treviso; Antonio Montinaro, MD, Azienda Unità Sanitaria Locale
Lecce 1, Lecce; Roberto Bonmassari, MD, Ospedale S. Chiara, Trento; Enrico
Magagnini, MD, Azienda Ospedaliera Universitaria Pisana Ospedale S. Chiara,
Pisa; Giuseppe Steffenino, MD, Azienda Ospedaliera S. Croce e Carle, Cuneo;
Stefano Tonioni, MD, Ospedale S. Pietro Fatebenefratelli, Roma.
Angiographic Core Laboratory: Maria Antonietta
Bonardi, BSc, Monica Repetto, BSc, Mediolanum Cardio Research, Milano.
Statistical Analysis: Erminio Bonizzoni, BSc,
Silvano Milani, BSc, University of Milan, Italy; Fabio Bravi, MD, Mediolanum
Cardio Research, Milano.
Clinical Events Committee: Giuseppe Sangiorgi,
MD, Ospedale Columbus, Milano; Flavio Airoldi, MD, Ospedale San Raffaele,
Principal Investigators or Study Coordinators: Roberta
Rosso, MD, Policlinico San Matteo, Universita’ degli Studi di Pavia,
Pavia (30 patients); Paola Giacometti, MD, Ospedale S. Maria Nuova, Reggio
Emilia (28 patients); Paolo Ortolani, MD, Policlinico S. Orsola Malpighi,
Bologna (26 patients); Rocco Mongiardo, MD, Università Cattolica Sacro
Cuore di Roma, Policlinico A. Gemelli, Roma (20 patients); Giorgio Taverna,
MD, Azienda Ospedaliera SS Antonio e Biagio e Cesare Arrigo, Alessandria (18
patients); Emilia Solinas, MD, Ospedale Maggiore di Parma, Universita’
degli Studi di Parma, Parma (16 patients); Mario Bossi, MD, Ospedale A. Manzoni,
Lecco (14 patients); Francesco De Felice, MD, Azienda Ospedaliera S. Camillo
Forlanini, Roma (14 patients); Gaetano Quaranta, MD, Azienda Ospedaliera S.
Carlo, Potenza (12 patients); Mauro De Benedictis, MD, Ospedale Mauriziano
Umberto I, Torino (11 patients); Andrea Santarelli, MD, Ospedale Infermi,
Rimini (10 patients); Bruno Loi, MD, Azienda Ospedaliera G. Brotzu, Cagliari
(9 patients); Angelo Sante Bongo, MD, Unità Operativa di Cardiologia
Novara site 15, Novara (8 patients); Alessandro Daniotti, MD, Ospedale Cà
Foncello, Treviso (8 patients); Giuseppe Colonna, MD, Azienda Unità
Sanitaria Locale Lecce 1, Lecce (7 patients); Carmen Spaccorotella, MD, Policlinico
Mater Domini, Catanzaro (6 patients); Massimiliano Marini, MD, Ospedale S.
Chiara, Trento (5 patients); Andrea Pieroni, MD, Azienda Ospedaliera Universitaria
Pisana Ospedale S. Chiara, Pisa (5 patients); Eugenio La Scala, MD, Azienda
Ospedaliera S. Croce e Carle, Cuneo (5 patients); Roberto Serdoz, MD, Ospedale
S. Pietro Fatebenefratelli, Roma (3 patients).
Funding/Support: This study was largely supported
through institutional funds of the participating centers. There was complementary
funding from Cordis Italia, Milan, Italy.
Role of the Sponsor: The sponsor provided free
stents to the participating sites and was responsible for the logistics of
the trial. The sponsor had no role in the study design, data analysis, and
Independent Statistical Analysis: Drs Ardissino
and Cavallini and the contract research organization (CRO) Mediolanum Cardiovascular
Research had direct access to the raw data. The statistical analysis was performed
by Erminio Bonizzoni, who is an academic statistician at the University of
Milan. For this project he worked with Fabio Bravi (another independent statistician)
as consultants for Mediolanum Cardiovascular Research. The statistical analyses
were made independently of the sponsor, which had no access to the data. However,
another academic statistician, Silavano Milani, not employed by the sponsor
and without any relationship with the CRO, repeated the statistical analyses
and provided written confirmation that the results are correct.
Acknowledgment: We thank Silvano Milani, Scuola
di Specializzazione in Statistica Sanitaria, University of Milan, who performed
an independent statistical analysis and confirmed our results.