Analysis of 1-Year Clinical Outcomes in the SIRIUS Trial
A Randomized Trial of a Sirolimus-Eluting Stent Versus a Standard Stent in Patients at High Risk for Coronary Restenosis
Background— This study evaluated a large group of patients enrolled in a double-blind randomized trial of the sirolimus-eluting stent to document whether the initial clinical improvement seen in previous smaller series is maintained out to 12 months and to study the potential treatment effect in patient subsets known to be at increased risk of restenosis.
Methods and Results— A total of 1058 patients with de novo native coronary stenosis undergoing clinically indicated percutaneous coronary intervention were randomly assigned to sirolimus-eluting stent (533) or control bare stent (525). Procedural success and in-hospital outcomes were excellent and did not differ between the 2 groups. At 9 months, clinical restenosis, defined as target-lesion revascularization, was 4.1% in the sirolimus limb versus 16.6% in the control limb (P<0.001). At 12 months, the absolute difference in target-lesion revascularization continued to increase and was 4.9% versus 20% (P<0.001). There were no differences in death or myocardial infarction rates. In high-risk patient subsets, defined by vessel size, lesion length, and presence of diabetes mellitus, there was a 70% to 80% reduction in clinical restenosis at 1 year.
Conclusions— Placement of the sirolimus-eluting stent results in continued clinical improvement at 1 year after initial implantation, with significant reduction in clinical restenosis as defined by target-lesion revascularization. Between 9 and 12 months, the absolute reduction of clinical restenosis continues to increase. Even in high-risk subsets of patients, there is a 70% to 80% relative reduction in clinical restenosis at 12 months with this drug-eluting stent.
Received August 14, 2003; revision received October 31, 2003; accepted October 31, 2003.
Compared with other percutaneous techniques, including balloon angioplasty, the unique attribute of coronary stents has been their consistent ability to reduce restenosis rates by producing consistently large target-lesion lumens.1–5 Angiographic binary restenosis rates were reported to be ≈20% or lower during the early stent era of the mid-1990s.6–8 However, as stenting has been applied to more challenging coronary lesions, observed restenosis rates have drifted upward to 30% or even higher, largely because of the increasing prevalence of adverse risk factors for restenosis, including the presence of diabetes mellitus, small-vessel disease, and long lesion lengths.9–11
Attempts at identifying an effective antirestenosis therapy have been disappointing12,13 until the recent demonstration that placement of a drug-eluting coronary stent containing sirolimus (rapamycin) markedly reduces neointimal hyperplasia and the resulting restenosis.14 A subsequent trial of 238 patients at moderate risk of restenosis demonstrated no angiographic restenosis at 6 months.15 Whether this will translate directly into clinical improvement in patients and lesions at higher risk for restenosis or over a longer period of observation is unclear. The purpose of this study was to evaluate the effect of the sirolimus-eluting stent on clinical restenosis in a population of patients and lesions at increased risk for coronary restenosis using a large, blinded, controlled trial of patients randomized to sirolimus-eluting stents compared with standard stents. The large sample size also allowed evaluation of the potential treatment effect of the drug-eluting stent across patient subgroups defined by the known coronary restenosis risk factors.
The primary objective of this study was to compare the 9- to 12-month clinical outcome after coronary stenting with the sirolimus-eluting stent versus a standard stainless steel stent for treatment of patients with de novo coronary artery disease. This randomized, double-blind trial complied with the Declaration of Helsinki regarding investigation in humans and was approved for Investigational Device Exemption by the United States Food and Drug Administration (FDA), and all investigational sites received approval from their local institutional review boards.
Study Design and Eligibility Criteria
The trial was performed at 53 North American centers (see Appendix) between February 2001 and September 2002.16 Selection criteria included patients who were willing and able to comply with the requirements of the protocol who had a history of angina and signs of myocardial ischemia clinically correlated with a de novo target lesion of >50% diameter stenosis, 15 to 30 mm in length, in a native coronary artery of 2.5 to 3.5 mm diameter based on angiographic visual estimates. Major exclusion criteria included (1) myocardial infarction within the previous 24 hours, (2) left ventricular ejection fraction <25%, (3) a target lesion located in an ostial or bifurcation location or one that had a thrombotic or severely calcified appearance, or (4) significant (>50% diameter) stenosis within the target coronary artery proximal or distal to the target lesion.
Before the index stent procedure, eligible patients were randomized with a 1:1 ratio in a double-blind fashion by the Interactive Voice Randomization System to 1 of the 2 treatments: a standard, base metal Bx Velocity balloon-expandable stent or sirolimus-eluting Bx Velocity (CYPHER, Cordis Corporation) balloon-expandable stent. Randomization was performed on a per-site basis to 1 of the 2 treatment arms, labeled respectively treatment A stents or treatment B stents. The investigator, the patient, and the nurse coordinator did not know whether a drug-eluting or standard stent was implanted.
Coronary Stent Procedure
All patients received oral aspirin (325 mg daily) and clopidogrel (loading dose of 300 to 375 mg, followed by a daily dose of 75 mg for 3 months) commencing 24 hours before the index procedure whenever possible. Intraprocedural intravenous heparin was given to maintain an activated clotting time of ≥250 seconds (>200 seconds if a glycoprotein IIb/IIIa inhibitor was used). Direct stenting was not allowed. After successful predilation of the target lesion, patients underwent implantation of either a standard Bx Velocity balloon-expandable stent or a sirolimus-eluting stent. The investigational sirolimus-eluting stent17 was available in 8- and 18-mm lengths and 2.5-, 3.0-, and 3.5-mm diameters and was identical in visual appearance to the control stent. Procedural success was defined as successful implantation of the study device, a final vessel diameter stenosis <50% (by visual inspection), and freedom from in-hospital major adverse cardiac events (MACE), defined as death, Q-wave myocardial infarction, and emergency CABG. Additional stents (using the randomly assigned stent type) were deployed only in the event of incomplete coverage of the lesion or edge dissection.
Data Collection and Follow-Up
Patients were evaluated clinically at 30 days and 6, 9, and 12 months. Detailed case report forms were completed by the clinical coordinators at each site, monitored by independent study monitors, and submitted to the data-coordinating center (CDAC/Harvard Clinical Research Institute, Harvard Medical School, Boston, Mass). An ECG was performed at baseline and was evaluated by an independent ECG core laboratory blinded to the treatment assignment (HCRI ECG Core Laboratory, Boston, Mass).
Angiograms were obtained in multiple views of the target lesion after intracoronary nitrates. All films were submitted to the angiographic core laboratory (Brigham and Women’s Angiographic Core laboratory, Boston, Mass), where they were analyzed with a computer-based system (Medis). Repeat angiography was performed in all patients who developed recurrent signs and symptoms of myocardial ischemia. Protocol-driven repeat angiography was planned after 240±30 days’ follow-up in the first 850 randomized patients.
All clinical end points were adjudicated by an independent Clinical Events Committee blinded to the treatment assignment. An independent Data Safety Monitoring Board reviewed the data to identify potential safety issues related to the conduct of the study. No member of this board was affiliated with the study sponsor or participated in this trial.
Study End Points
Although the primary end point for the trial was target-vessel failure, this study focuses on clinical restenosis (target-lesion revascularization [TLR]). Clinical restenosis was defined as TLR, which was any clinically driven repeat percutaneous intervention of the target lesion or bypass surgery of the target vessel that was performed for a clinical indication. Clinically driven revascularizations were those in which the patient had a positive functional study, ischemic ECG changes at rest in a distribution consistent with the target vessel, or ischemic symptoms and an in-lesion diameter stenosis by quantitative coronary angiography of ≥50%. In addition, in the absence of the above-mentioned ischemia, an in-lesion diameter stenosis by quantitative coronary angiography ≥70% was also considered “clinically driven.” The Clinical Events Committee blindly adjudicated all clinically driven revascularizations. Target-vessel revascularization but non-TLR was defined as any clinically driven repeat percutaneous intervention of the target vessel or bypass surgery of the target vessel for a lesion other than the target lesion within the target vessel. Target-vessel failure was defined as target-vessel revascularization, cardiac death, or Q-wave and non–Q-wave myocardial infarction not clearly attributed to a vessel other than the target vessel. Secondary clinical end points included a composite of MACE including death, Q-wave and non–Q-wave infarction, emergent bypass surgery, or repeat TLR at 30 days and 9 and 12 months after the index procedure. A non–Q-wave myocardial infarction was defined as an increase in the creatine kinase level to more than twice the upper limit of the normal range accompanied by an increased level of creatine kinase-MB in the absence of new Q waves on the ECG.
The effectiveness analysis and the safety evaluation were performed on a modified intent-to-treat population; deregistered patients were not included in the analysis because they received neither study treatment (see below). The treatment group differences were evaluated with the ANOVA for continuous variables. Cochran-Mantel-Haenszel or Fisher’s exact statistics, controlling for the site groups, were used for the categorical variables. Event-free composites during a 12-month follow-up period were analyzed by the Kaplan-Meier method. The differences between the 2 survival curves were compared with the log-rank test. A statistical significance was declared if the 2-sided probability value was <0.05. Stepwise logistic regression was used to identify factors related to the occurrence of TLR and MACE. For the stepwise procedure, an entry criterion probability value of 0.20 and a stay criterion of 0.10 were used. All statistical analyses were performed with SAS software (version 6.12).
Baseline Study Characteristics
Between February and August 2001, 1101 patients were enrolled. After blinded randomization, 43 patients (4% overall, 23 in the sirolimus arm and 20 in the control arm) were deregistered from the trial and did not receive the assigned treatment, which resulted in a final sample size of 1058 patients in whom investigational stent deployment was actually attempted. Of these, 533 patients (533 lesions) were assigned to the sirolimus-eluting stent and 525 patients (531 lesions) to the control standard stent.
The 2 groups were well matched, with an average age of 62 years, a 71.2% prevalence of men, and 26.4% prevalence of diabetes (Table 1). Average left ventricular ejection fraction was 55.9%, prior myocardial infarction had occurred in 30.6%, prior percutaneous coronary interventions (PCI) had been performed in 24.7%, and prior coronary bypass surgery had been performed in 9.5%. Percutaneous coronary intervention was indicated for Braunwald class 2 or 3 unstable angina in 42.9%; 41.6% had 2- or 3-vessel coronary artery disease. The target lesion had an average length of 14.4 mm, was classified as B or C according to the American College of Cardiology–American Heart Association classification in 92.4% of cases, and was located in the left anterior descending artery in 43.6% of patients.
Procedural Factors and Acute (In-Hospital) Results
Both groups were treated similarly by conventional interventional modalities, which included glycoprotein IIb/IIIa inhibitors, at the discretion of the investigator, in 59.8% (Table 1). Procedural success was achieved in 97.4% in the sirolimus arm and 98.5% in the placebo arm (P=0.28). In 27.7%, 2 or more stents were used, for an average of 1.4 stents per patient (not different between groups). The final average stent length was 21.4 mm, with a 1.6:1.0 stent-length–to–lesion-length ratio. Both groups had a low incidence of in-hospital adverse events (Table 2), with no difference between the 2 groups. There was only 1 in-hospital death in the entire study, and only 2 Q-wave myocardial infarctions. Stent thrombosis did not occur. The total MACE rate was 2.4% in the sirolimus arm and 1.5% in the control arm (P=0.379).
At 9 months (Table 3), there were significant differences in favor of the sirolimus-eluting stent, almost completely driven by improved rates of TLR. Neither death nor myocardial infarction was different between the 2 groups. Clinical restenosis (TLR) was markedly lower in the sirolimus group at 4.1% versus 16.6% (P<0.001). Target-vessel failure occurred in 47 of the sirolimus stent patients compared with 110 control patients (8.8% versus 21.0%, P<0.001). Stent thrombosis rates were comparable between the 2 groups (0.4% and 0.8% for sirolimus and control, respectively). As previously documented, this dramatic improvement in outcome is largely the result of the marked reduction in restenosis rates with sirolimus. Angiographic binary restenosis within the stent was 3.2% versus 35.4%, respectively, for sirolimus versus control stents; the corresponding rates for in-segment restenosis were 8.9% and 36.3%, respectively.16
At 12 months (Table 3), these significant differences remained. There was still no difference in the end point of death or myocardial infarction, and there was only a minimal increase in these end points in either group. The striking difference in TLR remained and even widened. At 9 months, the TLR rate for the sirolimus-eluting stent was 4.1%, whereas at 12 months, the TLR rate was 4.9%; this contrasts with the control stent group, in which the respective event rates were 16.6% and 20.0% (P<0.001 at both time points). Thus, the 12.5 percentage point absolute incremental benefit with the sirolimus-eluting stent at 9 months increased to 15.1 percentage points (151 per 1000 treated) at 1 year. The indication for TLR was typically recurrent angina (96.2% for sirolimus-eluting and 81.0% for control stent patients). A positive functional test formed part of the decision to proceed with TLR in 15.4% of sirolimus stent patients versus 19.0% of controls. The striking differences in event-free survival based on TLR, MACE, and target-vessel failure at 12 months are shown in Figure 1. In the patients who did not undergo mandated protocol angiographic follow-up, there was also an increase in the magnitude of difference between the TLR in the 2 groups, from 9.2% to 14.0% absolute reduction in TLR (Figure 2).
Factors associated with 12-month TLR were evaluated with a multiple logistic regression analysis in the entire group and in the sirolimus stent group alone (Table 4). In the entire group (Table 4), only 6 factors were associated with TLR, with treatment group being most important, followed by total stent length, postprocedure in-stent minimum lumen diameter, history of diabetes, prior CABG, and Canadian Cardiovascular Society class III or IV. In the sirolimus stent–treated patients (Table 4), only postprocedure in-stent minimum lumen diameter was significantly associated with TLR.
Risk Factor and Treatment Effect Analysis
The interaction of known restenosis risk factors (diabetes mellitus, vessel size, and lesion length) with the sirolimus treatment effect on clinical restenosis was evaluated by multivariable logistic regression modeling of 12-month TLR. Diabetes mellitus (OR 1.74, P=0.007), reference-vessel diameter (OR 0.50, P=0.002), and lesion length (OR 1.04, P=0.006) were significant determinants of TLR. Treatment assignment to sirolimus stents was associated with significant reduction in TLR (OR 0.21, P<0.001). There were no detectable significant treatment interactions that would suggest a lack of clinical antirestenosis benefit for sirolimus-eluting stents in subset patients including diabetes mellitus or variations in vessel diameter or lesion length (Figure 3).
There was a 70% to 80% relative reduction in clinical restenosis rate at 12 months with the sirolimus stent compared with the control stent irrespective of presence or absence of diabetes mellitus, vessel size, and lesion length based on predicted values from multiple logistic regression models (Table 5). Even in the highest-risk group (diabetes mellitus with reference-vessel diameter <2.5 mm and lesion length >15 mm), there was a 71% reduction.
Sirolimus-eluting stents have considerable promise for reducing the rate of restenosis, as assessed by quantitative angiography, intravascular ultrasound, and clinical parameters.14,15,17 The major finding of this SIRIUS analysis is that 12-month clinical restenosis, defined as blindly adjudicated TLR, is dramatically reduced from 20.0% in the control group to 4.9% in sirolimus-eluting stent–treated patients. Furthermore, the reduction in clinical restenosis between the 2 stent groups was concordant among all patient and lesion subsets.
Stent implantation is the dominant form of percutaneous coronary revascularization. This practice pattern has been the result of documented improved outcome compared with conventional coronary dilation because of the dramatic reduction in need for emergency coronary bypass surgery and a moderate but significant reduction in restenosis.18 In the recently completed PRESTO (Prevention of Restenosis with Tranilast and its Outcomes) trial of 11 500 patients, angiographic restenosis was seen in 33%.12 Therefore, although restenosis rates have improved with stent implantation, the restenotic process has not been eliminated. In some patients with unfavorable angiographic characteristics or clinical predictors of restenosis, restenosis has been very recalcitrant to therapy.
The development of drug-eluting stents offers the potential to take advantage of the positive attributes of stenting while further improving the results. With the sirolimus stent, the First In Man experience was confined to 45 patients, none of whom were found to have angiographic restenosis at the time of 4- to 12-month follow-up angiography,14 and was corroborated by the subsequent 238-patient Randomized Study With Sirolimus-Coated BxVelocity Balloon Expandable Stent (RAVEL) trial, which identified no angiographic restenosis at 6 months in the sirolimus stent group compared with 26.6% in the control stent group. Although this early experience with sirolimus was very encouraging and has also been reported with paclitaxel-eluting stents,19 that has not uniformly been the case with other drugs, coatings, or delivery vehicles.20 Although the QuaD DS drug-eluting stent with multiple nonbiodegradable polyacrylate sleeves that release a paclitaxel derivative was initially promising, subsequent studies documented a 10.2% incidence of 30-day MACE. Although the 6-month angiographic restenosis rate was 13.3%, it had increased to 61.5% at 12 months.20 There has also been concern about the potential effect of polymer coating on the vessel wall, because early animal data documented that during polymer degradation, there was marked inflammation with ongoing arterial wall injury.21
The SIRIUS trial provides convincing data in 1058 patients of the initial and, more importantly, sustained clinical improvement when native coronary artery lesions are treated with this specific drug-eluting stent. At 12 months, clinical restenosis defined as clinically driven TLR remained markedly improved with the drug-eluting stent; TLR was required in only 4.9% of patients compared with 20.0% of the control stent group. This was because restenosis rates were significantly decreased from 35.4% to 3.2% within the axial stent and from 36.3% to 8.9% within the stented segment, which includes 5 mm proximal and distal to the stent, at the time of 8-month angiographic assessment.16 Death and myocardial infarction rates were not significantly different between the 2 groups at 12 months. In contrast to studies with some drugs and delivery vehicles in which initial 6-month improvement was negated by 12-month events, the present study with the sirolimus-eluting stents out to 12 months documented that the absolute incremental benefit in TLR rate with the sirolimus-eluting stent actually increased from 12.5% at 9 months to 15.1% at 12 months. There was a concordant increase in freedom from MACE and target-vessel failure at 1 year.
Irrespective of lesion length, diameter of reference vessel, and presence or absence of diabetes, all factors associated with increased restenosis with bare stents, there was a 70% to 80% relative reduction in clinical restenosis with sirolimus stents in each of these groups. Concordant improvement in TLR was seen irrespective of the clinical subset of patients treated with the drug-eluting stent, including those with left anterior descending artery lesion location.
Despite the finding of no restenosis in the RAVEL trial, restenosis did occur with the sirolimus-eluting stent in the present trial. One reason that the restenosis rate might have been higher in the SIRIUS trial compared with RAVEL may relate to the inclusion of patients with more adverse baseline characteristics for restenosis (Table 6). As can be seen, factors known to be associated with restenosis tended to be more frequent in the patients in the SIRIUS study than in those in the RAVEL study. However, in the SIRIUS trial patients who received the sirolimus-eluting stent, these known risk factors for restenosis were not predictors of MACE at 1 year. Only 1 variable was significantly associated with MACE at 1 year, namely, a history of prior myocardial infarction (P=0.011).
This study confirms and extends the results observed in the RAVEL trial with the sirolimus-eluting stent in a group of patients and lesions at increased risk of restenosis. It also demonstrates that the large treatment effect observed is consistent across all subgroups studied and that the efficacy continues to improve out to 1 year without any evidence of untoward effects, even in patients with increased risk of restenosis. Although these results are very encouraging, it remains to be determined definitively whether a similar marked improvement in outcomes with the sirolimus-eluting stent will be observed in other patient groups at even higher risk of restenosis, including those with in-stent restenosis, total occlusions, and multivessel stenting.
The following investigators and institutions participated in the SIRIUS trial: Sponsor—Cordis, a Johnson and Johnson company, Warren, NJ, D. Donohoe (Medical Director), J. Jaeger (Program Director), E. Keim, L. Lonzetta, L. Reynolds, J. Batiller, C. Hill. Data and Safety Monitoring Board—B. Gersh (Chairperson), Rochester, Minn; M. Farkouh, New York, NY; R. Bonow, Chicago, Ill; R. D’Agostino (Biostatistician), Boston, Mass; G. Mintz, Washington, DC; A. Schwartz, New York, NY. Data Management—Harvard Clinical Research Institute, Boston, Mass. Coordination—E. Catapane. Clinical Events Committee— D. Cohen (Chairman), L. Epstein, J. Kannam, W. Manning, J. Markis; ECG Core Laboratory—P. Zimetbaum, M. Josephson. Core Angiographic Laboratory—Brigham and Women’s Hospital, Boston, Mass, J. Popma (Director). Core Intravascular Ultrasound Laboratory—Stanford University Medical Center, Stanford, Calif, P. Fitzgerald (Director). Clinical Sites—J. Carrozza, P. Rooney, Beth Israel Deaconess Medical Center, Boston, Mass; S. Ellis, A. Robakowski, The Cleveland Clinic Foundation, Cleveland, Ohio; J. Douglas, P. Hyde, Emory University Hospital, Atlanta, Ga; J. Moses, M. Leon, V. Laroche, Lenox Hill Hospital, New York, NY; P. Teirstein, E. Anderson, Scripps Clinic, La Jolla, Calif; E. Perin, M. Harlan, Texas Heart Institute, Houston, Tex; R. Wilensky, M. Walsh, Hospital of the University of Pennsylvania, Philadelphia, Pa; L. Satler, J. Lavoie, Washington Hospital Center, Washington, DC; M. Cleman, C. Roberts, Yale University Hospital, New Haven, Conn; S. DeMaio, L. Rogers, Baylor Medical Center, Dallas, Tex; E. Fry, A. Taylor, M. Potrikus, Saint Vincent’s Hospital, Indianapolis, Ind; A. Yeung, C. McWard, Stanford University Medical Center, Stanford, Calif; J. Zidar, S. Dickerson, Duke University Medical Center, Durham, NC; W. O’Neill, K. Dimick, William Beaumont Hospital, Royal Oak, Mich; G. Mishkel, J. Daniels, P. Sullivan, Saint John’s Hospital, Springfield Ill; D. McCormick, L. Mark, B. Connor, Hahnemann Hospital, Philadelphia, Pa; D. Roberts, B. Seiler, Sutter Memorial General Hospital, Sacramento, Calif; D. Holmes, D. Shelstad, Saint Mary’s Hospital, Rochester, Minn; F. Kiernan, D. Murphy, Hartford Hospital, Hartford, Conn; M. Midei, E. Yaker, Saint Joseph’s Hospital, Baltimore, Md; D. Williams, J. Muratori, T. Chaffee, Rhode Island Hospital, Providence, RI; T. Fischell, S. Baskerville, Borgess Medical Center, Kalamazoo, Mich; S. Oesterle, I. Palacios, C. Cothern, Massachusetts General Hospital, Boston, Mass; S. Yakubov, C. Gilliland, P. Vieira, Riverside Methodist Hospital, Columbus, Ohio; D. Kereiakes, R. Lengerich, The Christ Hospital/The Lindner Center, Cincinnati, Ohio; C. Davidson, L. Eckman, Northwestern Memorial Hospital, Chicago, Ill; C. Brown, K. Reid, Piedmont Hospital, Atlanta, Ga; C. Lambert, T. Watts, N. Parker, Health First Institute, Melbourne, Fla; D. Baim, R. Monboquette, Brigham and Women’s Hospital, Boston, Mass; A. Raizner, R. Benfield, The Methodist Hospital, Houston, Tex; B. Cohen, R. Lao, Morristown Memorial Hospital, Morristown, NJ; N. Laufer, M. Balfour, Good Samaritan Regional Medical Center, Phoenix, Ariz; S. Raible, B. J. Henehan, Jewish Hospital Heart & Lung Institute, Louisville, Ky; P. Coleman, A. Nofi, Northern California Medical Association, Santa Rosa, Calif; S. Sorenson, K. Robinson, Latter Day Saints Hospital, Salt Lake City, Utah; M. Mooney, P. Demmer, Abbott Northwestern Hospital, Minneapolis, Minn; T. Feldman, J. Lopez, L. Loftis, University of Chicago Hospitals, Chicago, Ill; J. Lasala, K. Zuchowski, S. Aubuchon, Barnes Jewish Hospital, Saint Louis, Mo; R. Caputo, C. Lastinger, Saint Joseph’s Hospital, Syracuse, NY; C. O’Shaughnessy, T. Julio, L. St. Marie, L. Barr, North Ohio Heart Center, Elyria, Ohio; H. Madyoon, T. Weaver, Saint Joseph’s Medical Center, Stockton, Calif; J. Midwall, L. Herlan, JFK Memorial Hospital, Atlantis, Fla; M. Bates, L. Lukhart, Charleston Area Medical Center, Charleston, WV; M. Clark, L. Pennington, Integris Oklahoma Heart Institute, Oklahoma City, Okla; T. Vellinga, K. McCormick, S. Congemi, Saint Luke’s Medical Center, Milwaukee, Wis; C. Simonton, C. Dellinger, G. Schwartz, Sanger Clinic, Charlotte NC; F. Leya, D. Jednachowski, Loyola University Medical Center, Maywood, Ill; G. Chapman, D. Gargus, University of Alabama, Birmingham, Ala; M. Reisman, F. Clouarte, Swedish Heart Hospital, Seattle, Wash; S. Wong, D. Reynolds, Cornell University New York Presbyterian Hospital, New York, NY; T. Bass, G. Morris, V. Brooks, University of Florida Health Science Center, Jacksonville, Fla; B. Bachinsky, A. Todd, C. Schaeffer, R. Yost, Harrisburg Hospital, Wormleysburg, Pa; M. Buchbinder, J. Logan, The Foundation for Cardiovascular Medicine, La Jolla, Calif.
Dr Fischell has served as a consultant for Cordis/Johnson & Johnson, is a shareholder in Johnson & Johnson, and is a coinventor of the Bx Velocity stent. Dr Moses owns common stock in and has served as a consultant to and speaker for Cordis/Johnson & Johnson. Dr Popma has received research grants for angiographic core laboratory activities. Dr Leon owns equity in, has received research grants from, and serves as a consultant to Johnson & Johnson. Dr Snead is an employee of Cordis.
The 1-year clinical outcome was assessed in 1058 patients enrolled in a randomized trial of a sirolimus-eluting stent or a control bare stent (SIRIUS). Clinical restenosis was defined as target-lesion revascularization, which was any clinically driven repeat percutaneous intervention of the target lesion or bypass surgery of the target vessel. At 9 months, the target-lesion revascularization rate for the sirolimus-eluting stent was 4.1% versus 16.6% in the control bare stent (P<0.001). At 12 months, this difference had widened to 4.9% versus 20.0% (P<0.001). Even in high-risk patient and lesion subsets, there was a 70% to 80% relative reduction in clinical restenosis at 12 months with the drug-eluting stent.
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