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Comparison of Effectiveness and Safety of Sirolimus-Eluting StentsVersus Bare-Metal Stents in Patients With Diabetes Mellitus (from

the Italian Multicenter Randomized DESSERT Study)

leardo Maresta, MDa,*, Elisabetta Varani, MDa, Marco Balducelli, MDa, Ferdinando Varbella, MDb,Corrado Lettieri, MDc, Lucia Uguccioni, MDd, Pietro Sangiorgio, MDe, and

Giuseppe Biondi Zoccai, MDf, for the DESSERT Investigators

Few studies directly compared drug-eluting stents and bare-metal stents (BMSs) in diabeticpatients. DESSERT was an Italian multicenter randomized trial to show the efficacy ofsirolimus-eluting stents (SESs) compared with BMSs in de novo lesions of diabetic patientstreated with insulin and/or oral antidiabetics for >3 months on top of glycoprotein IIb/IIIainhibitors. The primary end point was in-stent late lumen loss, assessed using centralizedquantitative coronary angiography at 8-month follow-up. Centrally adjudicated compositemajor adverse cardiac events (MACEs) and target-vessel failure (TVF; death, treatedvessel–related acute myocardial infarction, and target-vessel revascularization) at 30 daysand 9 and 12 months were secondary end points. Seventy-five patients were randomlyassigned to an SES (109 lesions), and 75 (109 lesions), to a BMS. The 2 groups were wellbalanced for clinical, anatomic, and procedural characteristics. In-stent late lumen lossdecreased from 0.96 � 0.61 mm for BMSs to 0.14 � 0.33 for SESs (p <0.001), andin-segment binary restenosis was 38.8% versus 3.6%, respectively (p <0.001). Twelve-month clinical events were significantly lower in the sirolimus group: MACEs 22.1% versus40% (p � 0.023), target-lesion revascularization 5.9% versus 30% (p <0.001), and TVF14.7% versus 34.3% (p � 0.008). At multivariate analysis, stent type was confirmed as anindependent predictor of in-segment late loss (p <0.001), binary restenosis (p <0.001),12-month TVF (p � 0.010), and 12-month MACEs (p � 0.037). In conclusion, therandomized DESSERT showed SESs to be safe and effective in decreasing both angio-graphic parameters of restenosis and incidence of MACEs compared with BMSs in diabeticpatients with de novo 1- or 2-vessel coronary stenoses. © 2008 Elsevier Inc. All rights

reserved. (Am J Cardiol 2008;101:1560–1566)

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he best revascularization strategy in diabetic patients istill controversial1 because of higher long-term mortalityith balloon or bare-metal stent (BMS) percutaneous cor-nary intervention (PCI) than with bypass surgery,2–6

igher rate of repeated revascularization, and poorer prog-osis with respect to nondiabetic patients.7,8 Only a fewandomized trials with small numbers of patients were de-igned specifically to address drug-eluting stents in diabeticatients.9,10 Data from diabetic subgroups in randomizedontrolled trials11–15 or registry studies16,17 showed that theeneficial effect of drug-eluting stents could be attenuatedn diabetic patients compared with that observed in patients

aDepartment of Cardiology, S. Maria delle Croci Hospital, Ravenna;Degli Infermi Hospital, Rivoli (Torino); cCarlo Poma Hospital, Mantova;S. Salvatore Hospital, Pesaro; eMaggiore Hospital, Bologna; and fDivisionf Cardiology, University of Turin, S. Giovanni Battista-Molinette Hospi-al, Torino, Italy. Manuscript received November 19, 2007; revised manu-cript received and accepted January 25, 2008.

This work was supported by a grant from Cordis Corp., Johnson &ohnson, Warren, New Jersey.

*Corresponding author: Tel: �39-0544-285-388; fax: �39-0544-285-95.

aE-mail address: ra.cardiologia@ausl.ra.it (A. Maresta).

002-9149/08/$ – see front matter © 2008 Elsevier Inc. All rights reserved.oi:10.1016/j.amjcard.2008.01.040

ithout diabetes, with restenosis rates still significantlyigher than in patients without diabetes.

The aim of this study was to compare clinical and an-iographic outcomes between sirolimus-eluting stentsSESs) and matching BMSs for 1- or 2-vessel PCI for deovo coronary stenosis in diabetic patients treated withnsulin and/or oral antidiabetics for �3 months on top of theest medical therapy, including glycoprotein IIb/IIIa inhib-tors during the procedure.

ethods

he Diabetes Drug Eluting Sirolimus Stent Experience inestenosis Trial (DESSERT) was an Italian multicenter,rospective, randomized, single-blind study. Principal investi-ators of the participating centers are listed in the Appendix.he study protocol was approved by local ethic committees atll 11 investigational sites. Written informed consent was ob-ained from all patients before randomization.

Eligibility criteria for the study were (1) diabetes melli-us on insulin and/or oral hypoglycemic agent treatment for

3 months, (2) symptoms or objective evidence of myo-ardial ischemia, and (3) 1 to 3 de novo significant coronaryesions in 1 or 2 coronary arteries. Stenosis had to be

menable for stent implantation after balloon predilation,

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1561Coronary Artery Disease/SES vs BMS in Diabetic Patients

ith target-vessel diameter �2.5 and �3.5 mm and lesionength �13 and �25 mm (assessed visually using angiog-aphy) and baseline Thrombolysis In Myocardial Infarctionow �2. Exclusion criteria included diabetes of recentiagnosis or treated with diet only or drugs for �3 months,24-hour ST-elevation myocardial infarction, non–ST-ele-

ation acute coronary syndrome with creatine kinase-MBwice the upper normal limit at the time of PCI, unprotectedeft main, bypass graft lesion, restenotic lesions, bifurcationesions, chronic total occlusion, left ventricle ejection fraction

30%, Thrombolysis In Myocardial Infarction flow 0 to 1,erum creatinine �3 mg/dl, previous stent �5 mm awayrom the lesion to be treated, other lesion treated �6 monthsefore, known allergy to aspirin and clopidogrel, decreasedife expectancy, and noncompliance with follow-up.

Randomization was accomplished at each site using thenteractive Voice Randomization System. Eligible patientsere centrally randomly assigned to an SES (Cypher andypher Select; Cordis Corp., Johnson & Johnson, Warren,ew Jersey) or BMS (Sonic; Cordis Corp.) in a 1:1 ratio.he randomization sequence was concealed until the inter-ention was assigned.

Coronary angioplasty was performed according to stan-ard practice. Per-protocol balloon predilation was per-ormed using a balloon shorter than the stent required in anttempt to avoid geographic miss. Allowed stents were 13,8, 23, and 28 mm in length and 2.5, 2.75, 3.0, and 3.5 mmn diameter. Multiple stent implantations for a single lesionere allowed only to cover a proximal or distal dissection

fter initial stent implantation. Postdilation of the stent withigher pressure or larger balloon was performed at theperator’s discretion to obtain �30% visual residual steno-is. When multisegment or multivessel treatment was per-ormed, all implanted stents had to be of the same randomlyssigned type.

All patients were treated with oral aspirin (100 mg/day)nd clopidogrel (loading dose 300 mg, then 75 mg/day).uration of clopidogrel therapy was 2 months in the Sonicroup and in a few initial patients in the Cypher groupccording to the treatment schedule of the Ravel Study.18

n amendment of the protocol thereafter required 6 monthsf clopidogrel therapy for all patients in the Cypher group.uring the procedure, an intravenous 70-IU/kg heparin bolus

nd glycoprotein IIb/IIIa inhibitors (abciximab 0.25-mg/kg bo-us followed by 0.125 �g/kg/min or tirofiban 0.4 �g/kg/min in0 minutes followed by 0.1 �g/kg/min as upfront acute coro-ary syndrome treatment) were administered.

Clinical, procedural, and laboratory analysis data wereollected using a paper case report form and sent to aentralized coordinating center (Mediolanum Cardio Re-earch, Milan, Italy). Clinical baseline and follow-up infor-ation were obtained by the research coordinator at each

ite during hospitalization, at 30 days, and at 9 and 12onths. All clinical end points were adjudicated by an

ndependent clinical events committee that was unaware ofhe treatment assignments.

Laboratory analysis included baseline and 30-day stan-ard examinations plus hemoglobin A1c and C-reactiverotein; baseline and 6-, 12-, and 24-hour creatine ki-ase-MB and troponin monitoring; and 24-hour hemoglobin

nd renal function control. 8

Coronary angiograms, obtained at baseline, end of thetenting procedure, and 8-month follow-up and performedn �2 orthogonal views after intracoronary injection ofitroglycerin using a �6 Fr guiding catheter, were recordedn CD-ROM and submitted to the independent angio-raphic core laboratory (Mediolanum Cardio Research).uantitative angiographic analysis was blinded to treatment

ssignment and done with the use of a computer-basedystem (QCA-CMS 5.2; Medis, Leiden, The Netherlands).ate lumen loss was defined as the difference betweeninimal luminal diameter obtained after the stenting proce-

ure and that measured during follow-up. Binary restenosisas defined as stenosis �50% of the luminal diameter in the

arget lesion at follow-up. Quantitative angiographic mea-urements of the target lesions were made in the “in-stent”one and “in-segment” zone (which included the stentedegment and margins 5 mm proximal and distal to the stent).

The primary end point of the study was in-stent late losst 8-month coronary angiography.

Secondary end points included major adverse cardiacvents (MACEs), defined as death, myocardial infarction (Qave and non–Q wave), emergent bypass surgery, or re-eated target-lesion revascularization at 30 days and 9 and2 months postprocedure; target-vessel failure (TVF), de-ned as cardiac death, treated vessel–related myocardial

nfarction, or target-vessel revascularization since dischargeo 12 months postprocedure; 12-month target-lesion revas-ularization and target-vessel revascularization; angio-raphic binary restenosis (�50% diameter stenosis) at 8onths postprocedure; and in-stent and in-segment minimal

uminal diameter at 8-month follow-up.Myocardial infarction after the procedure was defined as

he occurrence of prolonged typical chest pain and/or eitherhe development of pathological Q waves in �2 contiguouseads or increase in creatine kinase-MB to �3 times thepper limit of normal.

Stent thrombosis was defined according the Academicesearch Consortium recommendations19 and divided intocute (0 to 1 day), subacute (2 to 30 days) and late (31 dayso 1 year) and into definite, probable, and possible.

At the time of study design, a planned sample size of 250atients (125 for each group) was calculated to provide 80%tatistical power to detect a 30% difference in the primarynd point (from in-stent late loss of 1 mm in the BMS groupo 0.70 mm in the SES group with an SD of 0.7 mm and a-sided 5% � error) and account for �70% compliance with-month angiographic follow-up. Quantitative variablesere presented as mean � SD, and categorical variables, asercentages. The effectiveness analysis and safety evalua-ion were performed on an intent-to-treat population. Treat-ent group difference was evaluated using analysis of vari-

nce or Wilcoxon’s rank-sum scores for continuousariables. The Cochran-Mantel-Haenszel statistic was usedor categorical variables. The 95% confidence intervalsCIs) for the mean difference for treatment groups and the5% CIs of the risk and difference were provided for reste-osis rate, 12-month TVF rate, and each of the adverse-vent parameters presented. Mean differences and 95% CIsf differences between treatment groups were provided for

-month in-stent late loss. Occurrence of TVF and other

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1562 The American Journal of Cardiology (www.AJConline.org)

dverse-event composites during a 12-month follow-up wasnalyzed using the actuarial life table method. The differ-nce between the 2 survival curves was compared usingog-rank and Wilcoxon’s tests. To identify factors thatight be related to angiographic outcome and the occur-

ence of adverse events, linear and logistic regressions weresed, with the variables age, gender, diabetes type, hyper-ension, dyslipidemia, smoking status, admission diagnosis,

Figure 1. Study flowchart.

able 1aseline clinical characteristics

linical Characteristics SES Group(n � 75)

BMS Group(n � 75)

p Value

ge (yrs) 71 � 9 69 � 9 0.384en 47 (63%) 37 (49%) 0.137ody mass index (kg/m2) 28 � 4 27 � 3 0.052revious myocardial infarction 27 (36%) 19 (25%) 0.157revious coronary angioplasty 11 (15%) 8 (11%) 0.584revious coronary bypass 5 (7%) 3 (44%) 0.485revious cerebrovascular attack 4 (5%) 4 (5%) 0.672ypertension 58 (77%) 56 (75%) 0.246yperlipidemia 35 (47%) 39 (52%) 0.513moking history 32 (43%) 29 (39%) 0.614ype 1 diabetes mellitus 5 (7%) 8 (11%) 0.356

nsulin treatment in the last 3 mo 18 (24%) 20 (27%) 0.193ral hypoglycemics in the last 3 mo 67 (89%) 56 (75%) 0.019emoglobin A1c (g/dl) 7.5 � 1 8 � 2 0.039emoglobin A1c �7 g/dl 46 (61%) 49 (65%) 0.611bnormal C-reactive protein 45 (60%) 48 (64%) 0.676erum creatinine �2 mg/dl 27 (36%) 11 (15%) 0.022ndicationStable angina pectoris 22 (29%) 21 (28%) 0.228Unstable angina pectoris 35 (47%) 36 (48%)Recent myocardial infarction 12 (16%) 9 (12%)Silent myocardial ischemia 6 (8%) 9 (12%)eft ventricle ejection fraction (%) 59 � 15 62 � 12 0.095o. of coronary arteries narrowed1 21 (28%) 26 (35%) 0.6752 29 (38%) 26 (34%)

t3 25 (34%) 23 (31%)

aseline serum creatinine, hemoglobin A1c, C-reactive pro-ein, left ventricular ejection fraction, number of diseasedoronary vessels, glycoprotein IIb/IIIa use, and allocationroup tested. A statistical significance was declared for-sided p �0.05.

esults

rom January 2004 to April 2006, a total of 150 eligibleatients were included in the study. After a blinded interimnalysis that showed significantly better than expected re-ults with the Cypher stent, the trial was stopped. Seventy-ve patients with 109 treated lesions were allocated to theES group and 75 patients with 109 lesions were included

n the BMS group. The flow chart of the study is shown inigure 1.

Baseline characteristics are listed in Table 1. Globally,% of patients had insulin-dependent diabetes and 25%eceived insulin treatment in the last 3 months. The 2 groupsere well balanced for most coronary risk factors, cardiacistory, stable or unstable symptoms, left ventricle ejectionraction, and degree of coronary disease. Although the per-entage of patients with abnormal hemoglobin A1c was notifferent between the 2 groups, the mean value was highern patients treated with a BMS than with an SES, whichhowed more use of oral hypoglycemic agents.

Angiographic and procedural data were not significantlyifferent between the 2 groups (Table 2). Multivessel PCIas performed in 26.5% of patients. Lesions were predom-

nantly of type B2/C (62%), 59% had a reference vesseliameter �2.75 mm, and 22% had a length �20 mm. Sixatients in each group (8%) received upfront treatment withirofiban. All other patients were treated with abciximab at

able 2ngiographic and procedural characteristics

ariable SES Group(n � 109)

BMS Group(n � 109)

p Value

reated coronary artery/patientLeft anterior descending 45 (60%) 43 (57%) 0.731Left circumflex 27 (36%) 23 (31%) 0.591Right coronary artery 25 (33%) 29 (39%) 0.481o. of treated lesions/patient1 48 (65%) 50 (67%) 0.9522 23 (30%) 20 (27%)3 4 (5%) 5 (6%)esion typeA 4 (3%) 9 (8%) 0.407B1 36 (33%) 36 (33%)B2 52 (48%) 48 (44%)C 17 (16%) 16 (15%)tents implanted/lesion1 96 (88%) 101 (93%) 0.2022 12 (12%) 8 (7%)tent diameter (mm) 3.0 � 0.4 3.0 � 0.3 0.884tent length (mm) 20.3 � 5.0 19.4 � 4.4 0.166tent dilation pressure (atm) 13.8 � 1.9 13.8 � 2.3 0.829ostdilation after stenting 11 (10%) 20 (18%) 0.065ressure for postdilation (atm) 15.5 � 4.8 16.3 � 4.3 0.624

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1563Coronary Artery Disease/SES vs BMS in Diabetic Patients

In-hospital MACEs occurred in 9.3% of patients with noifference between the 2 groups. One patient in the BMSroup experienced a Q-wave myocardial infarction andcute renal failure and died of cardiogenic shock. Anotheratient in the same group experienced a cerebrovascularttack. Non–Q-wave postprocedural myocardial infarctionccurred in 7 (9.3%) and 6 patients (8.0%) treated withMSs and SESs, respectively. No case of urgent repeatedCI, bypass surgery, or acute or subacute stent thrombosisas observed. Only 1 major bleeding episode occurred afterES placement, treated using transfusion. Mean hospitaltay was 5.8 � 5.1 days, with no difference between the 2roups. Therapy at discharge included � blockers in 61.2%f patients, angiotensin-converting enzyme inhibitors in2.7%, statins in 64%, oral hypoglycemic agents in 68.3%,nd insulin in 36% of patients, with no difference betweenhe 2 groups.

At 30-day follow-up, 3 additional non–Q-wave myocar-ial infarctions occurred, 1 in the BMS group and 2 in theES group, with 2 target-vessel revascularizations in eachroup and 1 subacute stent thrombosis 6 days postprocedureor the SES group. Total MACEs were 12% in the SESroup and 13.9% in the BMS group (odds ratio [OR] 1.18,5% CI 0.41 to 3.43, p � 0.733). Only baseline C-reactiverotein was an independent predictor of 30-day TVF inultivariate analysis (OR 1.14, 95% CI 1.01 to 1.28, p �

.031). The reinforced antidiabetic therapy resulted in loweremoglobin A1c and lower percentage of patients withbnormal hemoglobin A1c in respect to predischarge data,ith no difference between groups (7.3 � 1.2% vs 7.2 �

able 3aseline post–percutaneous intervention and 8-month follow-up per lesion

ariable

n-segment baseline minimal luminal diameter (mm)n-segment baseline reference vessel diameter (mm)aseline lesion length (mm)aseline diameter stenosis (%)

n-stent post minimal luminal diameter (mm)n-segment post minimal luminal diameter (mm)n-segment post reference vessel diameter (mm)n-stent post diameter stenosis (%)n-segment post diameter stenosis (%)n-stent follow-up minimal luminal diameter (mm)n-segment follow-up minimal luminal diameter (mm)roximal edge follow-up minimal luminal diameter (mm)istal edge follow-up minimal luminal diameter (mm)

n-segment follow-up reference vessel diameter (mm)n-stent follow-up diameter stenosis (%)n-segment follow-up diameter stenosis (%)n-segment follow-up length of restenosis (mm)n-stent late loss (mm)n-segment late loss (mm)roximal edge late loss (mm)istal edge late loss (mm)

n-stent binary restenosis (%)roximal edge binary restenosis (%)istal edge binary restenosis (%)

.2% in the SES vs BMS groups, p � 0.577; hemoglobin �

1c �7% in 51% vs 57.7% of patients in the SES vs BMSroups, p � 0.501).

Acute results did not differ between the 2 groups (Table 3).he 8-month angiographic follow-up was performed as perrotocol in 76% of enrolled patients at mean times from thendex procedure of 8.2 � 1.5 months in the SES group and.5 � 1.8 months in the BMS group (p � 0.032) because ofore symptomatic patients in the latter group. Early clini-

ally driven angiographic follow-up was performed in 12%f the BMS group and 2.7% of the SES group (p � 0.028).esults of per-lesion bivariate quantitative coronary angiog-

aphy analysis are listed in Table 3. All angiographic pa-ameters were significantly better for the SES group atollow-up. Although overall binary angiographic restenosisas significantly higher in the BMS group (p �0.001), the

elative occurrence of restenosis patterns following the clas-ification of Mehran et al20 was not significantly associatedith stent type (1 lesion with type I, type II, and type III

estenosis in the SES group; 11 lesions with type I, 13 withype II, 6 with type III, and 1 with type IV restenosis in theMS group; p � 0.938).

Multivariate analysis showed that baseline in-segmentiameter stenosis and stent type were independent predic-ors of follow-up in-segment minimal luminal diameter andn-segment late loss. Baseline in-segment reference vesseliameter (OR 0.14, 95% CI 0.04 to 0.55, p � 0.035) andtent type (OR 25.3, 95% CI 6.58 to 97.64, p �0.001) werendependent predictors of follow-up in-segment binary re-tenosis. The SES beneficial effect on binary restenosis inespect to BMSs was present in men and women, patientsith previous and no previous insulin use, vessels �2.75 or

graphic results

ES Group(n � 84)

BMS Group(n � 80)

p Value

.77 � 0.35 0.80 � 0.36 0.577

.65 � 0.49 2.67 � 0.36 0.7364.7 � 7.1 15.1 � 7.0 0.69271 � 11.5 70 � 12.0 0.726.52 � 0.40 2.44 � 0.36 0.122.15 � 0.51 2.17 � 0.42 0.852.75 � 0.45 2.75 � 0.40 0.95611 � 7.5 12 � 6 0.60722 � 11 21 � 10 0.428.37 � 0.52 1.48 � 0.74 �0.001.12 � 0.49 1.44 � 0.71 �0.001.55 � 0.61 2.40 � 0.65 0.127.25 � 0.49 2.05 � 0.56 0.015.83 � 0.48 2.62 � 0.45 0.00321 � 13 46 � 23 �0.00126 � 11.5 46 � 23 �0.0015.8 � 3.4 12.0 � 7.4 �0.001.14 � 0.33 0.96 � 0.61 �0.001.05 � 0.36 0.75 � 0.66 �0.001.02 � 0.37 0.13 � 0.47 0.001.07 � 0.34 0.13 � 0.38 0.026

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1564 The American Journal of Cardiology (www.AJConline.org)

n regard to 9-month MACEs, the SES group showedetter results than the BMS group in men and patientsith no previous insulin use, multiple stenting per patient,essel diameter �2.75 mm. and lesion length �20 mm (all�0.05).Table 4 lists 12-month clinical events. From 30 days to

2 months, there were 3 deaths in the SES group (2 fromevere heart failure and 1 sudden death at 239 days) and 1udden death 190 days after the procedure in the BMSroup. A total of 59% of patients with target-lesion revas-ularization within 12 months in the BMS group and 66% inhe SES group were symptomatic. This translated to a symp-om-driven target-lesion revascularization rate of 17.0%ersus 4.4% (p � 0.016) and target-lesion revascularizationn asymptomatic patients of 12.9% versus 1.5% (p �.017). One patient in the BMS group experienced a latetent thrombosis that led to Q-wave myocardial infarctionnd urgent repeated PCI 4 months after the index procedure.

Multivariate analysis showed that hemoglobin A1c andtent type were independent predictors of TVF (hemoglobin1c OR 1.40, 95% CI 1.05 to 1.87, p � 0.024; stent typeR 2.97, 95% CI 1.29 to 6.84, p � 0.010), whereas only

tent type was an independent predictor of 12-month MACEOR 2.35, 95% CI 1.12 to 4.98, p � 0.024).

iscussion

his study allowed a direct randomized comparison be-ween BMSs and SESs in diabetic patients and confirmedES safety and efficacy with a significant decrease in 12-onth angiographic and clinical end points. Other small

andomized studies9,10 had similar results. At the time oftudy protocol definition, few data for drug-eluting stentafety and efficacy were available. Consequently, the studyesign contained many exclusion criteria comprehensive ofype of lesions still considered “off label,” but frequentlyncountered in diabetic patients. From the registry of alliabetic patients treated using PCI in the primary investi-ator’s center, where the highest number of patients werenrolled (n � 74), it was possible to infer that only 34% of

able 4er-patient bivariate analysis of 12-month clinical events

ariable BMS Group(n � 70)

ACEs 28 (40%)VF 24 (34.3%)eath 2 (2.9%)otal myocardial infarction 14 (20%)Q wave 3 (4.3%)Non–Q wave 11 (15.7%)oronary artery bypass graft 0 (0%)arget-lesion revascularization 21 (30%)arget-vessel revascularization 21 (30%)tent thrombosis 1 (1.4%)Acute 0 (0%)Subacute 0 (0%)Late 1 (1.4%)

ll-comers diabetic patients were enrolled in this study. The 0

nvestigated population had medium- to high-risk clinicalnd angiographic characteristics. Exclusion of such a par-icularly complex lesion subset as total chronic occlusions,ifurcations, ostial lesions, very long lesions, or lesions inery small vessels could partly explain the more importantbsolute and relative gain of SESs versus BMSs (MACEecrease of 43% and target-vessel revascularization decreasef 75%) observed in this study compared with the recentlyeported results in diabetic patients in registry data.16,17

To our knowledge, this is the only study of diabeticatients that required routine glycoprotein IIb/IIIa antago-ist therapy. Abciximab was shown to be effective in de-reasing early and long-term mortality in diabetic patientsreated with BMSs,21 and similar effects were common tother antagonists.22

Regarding safety, there was a single case of definiteubacute stent thrombosis in the SES group 6 days after therocedure and a case of definite late thrombosis (4 months)n the BMS group. Although dual antiplatelet treatment wastopped at 6 months, it is noteworthy to mention that thereas no late definite stent thrombosis in the SES group �6onths, confirming the midterm safety and effectiveness ofESs. If the 2 cases of sudden death are included, according

o the Academic Research Consortium definition of possibletent thrombosis,19 the total incidence of definite plus pos-ible stent thrombosis reached 2.6% in both groups, a rela-ively high figure, but not related to stent type.

Optimized glycemic control was shown to have a pro-ective effect in patients with diabetes.23 An uncontrolled

etabolic situation represented by hemoglobin A1c �7%ecreased from 63% of patients at the time of enrollment to4% at 30 days, and insulin-treated patients increased from5% to 36%. Whether these good results are reproducible inorse metabolic conditions commonly seen in daily clinicalractice remains to be proved. Patients in the BMS groupad worse metabolic control, notwithstanding an ameliora-ion at 30 days, and this could have contributed to theirorse clinical results. Notwithstanding the limited sample

ize of our study, hemoglobin A1c together with stent typeas the only independent predictor of 12-month TVF atultivariate analysis (OR 1.40, 95% CI 1.05 to 1.87, p �

ES Group(n � 68)

OR (95% CI) p Value

5 (22.1%) 2.36 (1.05–5.33) 0.0230 (14.7%) 3.03 (1.23–7.59) 0.0083 (4.4%) 0.64 (0.07–4.89) 0.6781 (16.2%) 1.30 (0.50–3.38) 0.5591 (1.5%) 3.00 (0.27–76.03) 0.6200 (14.7%) 1.08 (0.39–3.01) 0.8690 (0%) — 1.04 (5.9%) 6.86 (2.04–25.37) �0.0015 (7.4%) 5.4 (1.76–17.72) �0.0011 (1.5%) 0.97 (0.03–36.37) 1.00 (0%) — 1.01 (1.5%) 0.01 (0.00–17.00) 0.4930 (0%) — 1.0

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1565Coronary Artery Disease/SES vs BMS in Diabetic Patients

Quantitative coronary angiography results at follow-uponfirmed the optimal performance of SESs already shownn other studies of diabetic patients in terms of minimaluminal diameter, late loss, focal pattern of intimal hyper-lasia (when present), and absence of negative edge effectsoth proximally and distally to the stent. Great attention wasosed on an accurate technique of stent deployment in bothhe SES and BMS groups. In the BMS group, the prevalencef postdilation was even higher, probably because of aware-ess of the thick-strut stent’s employment bias and with thentention to optimize as much as possible the initial result.hick-strut stents were shown to be more susceptible to

estenosis than BMSs with thin struts.24

This study had the same limitations of all randomizedtudies dealing with precise enrollment criteria that cannote applied to all diabetic patients encountered in everydaylinical practice. However, the recent alarms for DES safetyn so-called off-label (not confirmed by randomized studies)linical and angiographic situations, such as bifurcations orotal chronic occlusions, emphasize the significance of theptimal results obtained in our diabetic population.

Use of a stainless steel BMS not of the latest generationould have led to worse results in the BMS group withoutffecting the very good results obtained with SESs. How-ver, it is recognized that thin-strut BMSs are the standardf care nowadays.

Because of the type of stents used and the impossibilityo render them undistinguishable, this study was not doublelind. However, primary and secondary angiographic endoints were analyzed by a blinded independent core labo-atory and clinical events were adjudicated by the indepen-ent events committee in a blinded manner.

ppendix

rincipal investigators and participating centers: Aleardoaresta, S. Maria delle Croci Hospital, Ravenna; Ferdinandoarbella, degli Infermi Hospital, Rivoli (TO); Roberto Zanini,arlo Poma Hospital, Mantova; Lucia Uguccioni, S. Salvatoreospital, Pesaro; Pietro Sangiorgio, Maggiore Hospital, Bo-

ogna; Antonino Nicosia, M.P. Arezzo Hospital, Ragusa;ilvio Klugmann, Niguarda Ca’Granda Hospital, Milano;rancesco Della Rovere, Galliera Hospital, Genova; Anto-io Manari, S. Maria Nuova Hospital, Reggio Emilia;chille Bravi, Le Scotte Hospital, Siena; Sergio Repetto,ircolo Fondazione Macchi Hospital, Varese.

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