High-dose 7-hexanoyltaxol-eluting stent with polymer sleeves for coronary revascularization: one-year results from the SCORE randomized trial. Randomized study to assess the effectiveness of slow- and moderate-release polymer-based paclitaxel-eluting stents for coronary artery lesions. Inhibition of restenosis with a paclitaxel-eluting, polymer-free coronary stent: the European evaLUation of pacliTaxel Eluting Stent (ELUTES) trial. Clinical efficacy of polymer-based paclitaxel-eluting stents in the treatment of complex, long coronary artery lesions from a multicenter, randomized trial: support for the use of drug-eluting stents in contemporary clinical practice. Maintenance of long-term clinical benefit with sirolimus-eluting coronary stents: three-year results of the RAVEL trial. 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. Sirolimus-eluting stents compared with standard stents in the treatment of patients with primary angioplasty. A polymer-based, paclitaxel-eluting stent in patients with coronary artery disease. Comparison of a polymer-based paclitaxel-eluting stent with a bare metal stent in patients with complex coronary artery disease: a randomized controlled trial.
The Study to COmpare REstenosis Rate between QueST and QuaDDS-QP2 (SCORE) trial was a multicenter, randomized, open-label trial comparing the safety and performance of 13- and 17-mm QuaDDS stents (n = 126) (Quanam Medical Corp., Santa Clara, California/Boston Scientific Corp., Natick, Massachusetts) versus uncoated control stents (n = 140) in focal, de novo coronary lesions.
                The pioneering drug-delivery QuaDDS stent used four to six acrylate polymer sleeves, each loaded with 800 microg of the paclitaxel derivative 7-hexanoyltaxol.
                Clinical end points were assessed at 1, 6, and 12 months post procedure. Quantitative coronary angiography and intravascular ultrasound were performed post procedure and at six-month follow-up.
                In the QuaDDS group, early stent thrombosis and myocardial infarction (MI) rates were significantly higher, leading to premature cessation of enrollment. For the QuaDDS group, the stent thrombosis rate increased from 3.2% to 10.3% between 1 and 12 months, associated with increased non-Q-wave MI and death rates. The angiographic restenosis rate at six months was reduced from 32.7% (control) to 7.4% (p < 0.0001). However, the primary end point was not met with six-month target vessel revascularization (TVR) rate as well as the composite major adverse cardiac event rates (cardiac death, MI, and TVR) comparable between groups.
                Despite angiographic indications of potential anti-restenotic benefit, increased rates of stent thrombosis, MI, and cardiac death associated with the QuaDDS stent show an unacceptable safety profile. Early clinical studies demonstrated the feasibility of local paclitaxel delivery in reducing restenosis after treatment of de novo coronary lesions in small patient populations.
                We conducted a randomized, double-blind trial of 536 patients at 38 medical centers evaluating slow-release (SR) and moderate-release (MR) formulations of a polymer-based paclitaxel-eluting stent (TAXUS) for revascularization of single, primary lesions in native coronary arteries. Cohort I compared TAXUS-SR with control stents, and Cohort II compared TAXUS-MR with a second control group. The primary end point was 6-month percent in-stent net volume obstruction measured by intravascular ultrasound. Secondary end points were 6-month angiographic restenosis and 6- and 12-month incidence of major adverse cardiac events, a composite of cardiac death, myocardial infarction, and repeat revascularization. At 6 months, percent net volume obstruction within the stent was significantly lower for TAXUS stents (7.9% SR and 7.8% MR) than for respective controls (23.2% and 20.5%; P<0.0001 for both). This corresponded with a reduction in angiographic restenosis from 17.9% to 2.3% in the SR cohort (P<0.0001) and from 20.2% to 4.7% in the MR cohort (P=0.0002). The incidence of major adverse cardiac events at 12 months was significantly lower (P=0.0192) in the TAXUS-SR (10.9%) and TAXUS-MR (9.9%) groups than in controls (22.0% and 21.4%, respectively), predominantly because of a significant reduction in repeat revascularization of the target lesion in TAXUS-treated patients.
                Compared with a bare metal stent, paclitaxel-eluting stents reduced in-stent neointimal formation and restenosis and improved 12-month clinical outcome of patients with single de novo coronary lesions. The use of a stent to deliver a drug may reduce in-stent restenosis. Paclitaxel interrupts the smooth muscle cell cycle by stabilizing microtubules, thereby arresting mitosis.
                On the basis of prior animal studies, the European evaLUation of the pacliTaxel Eluting Stent (ELUTES) pilot clinical trial (n=190) investigated the safety and efficacy of V-Flex Plus coronary stents (Cook Inc) coated with escalating doses of paclitaxel (0.2, 0.7, 1.4, and 2.7 microg/mm2 stent surface area) applied directly to the abluminal surface of the stent in de novo lesions compared with bare stent alone. The primary efficacy end point was angiographic percent diameter stenosis at 6 months. At angiographic follow-up, percent diameter stenosis was 33.9+/-26.7% in controls (n=34) and 14.2+/-16.6% in the 2.7-microg/mm2 group (n=31; P=0.006). Late loss decreased from 0.73+/-0.73 to 0.11+/-0.50 mm (P=0.002). Binary restenosis (> or =50% at follow-up) decreased from 20.6% to 3.2% (P=0.056), with no significant benefit from intermediate paclitaxel doses. Freedom from major adverse cardiac events in the highest (effective) dose group was 92%, 89%, and 86% at 1, 6, and 12 months, respectively (P=NS versus control). No late stent thromboses were seen in any treated group despite clopidogrel treatment for 3 months only.
                Paclitaxel applied directly to the abluminal surface of a bare metal coronary stent, at a dose density of 2.7 microg/mm2, reduced angiographic indicators of in-stent restenosis without short- or medium-term side effects. Intracoronary polymer-based stent delivery of paclitaxel has been shown to be effective in reducing restenosis in simple coronary lesions, but the evidence base for contemporary use in longer, more complex coronary stenoses is lacking.
                TAXUS VI is a prospective, multicenter, double-blind, randomized trial assessing clinical and angiographic outcomes of the TAXUS Moderate Release paclitaxel-eluting stent in the treatment of long, complex coronary artery lesions. Four hundred forty-eight patients at 44 sites were randomized (1:1) between a drug-eluting TAXUS Express2 and an uncoated Express2 control stent. Per protocol, the 9-month follow-up included an angiographic reevaluation in all patients. The primary end point was the rate of target-vessel revascularization 9 months after the study procedure; secondary end points included the rate of target-lesion revascularization and binary restenosis at follow-up. Mean lesion length in the study was 20.6 mm, with a mean stent-covered length of 33.4 mm. Of all lesions, 55.6% were classified as complex lesions (type C of the AHA/ACC classification). At 9 months, target-vessel revascularization was 9.1% in the TAXUS group and 19.4% in the control group (P=0.0027; relative reduction, 53%). Target-lesion revascularization was reduced from 18.9% to 6.8%, respectively (P=0.0001). The incidence of major adverse cardiac events was similar in the 2 groups, 16.4% and 22.5% in TAXUS and control, respectively (P=0.12), including comparable rates for acute myocardial infarction. Binary restenosis in the stented area was reduced from 32.9% in the control group to 9.1% in the TAXUS patients (P<0.0001).
                The finding that the TAXUS Moderate Release stent system is safe and effective in the treatment of long, complex coronary artery lesions provides the evidence base for the more widespread use of drug-eluting stents in contemporary clinical practice. The use of sirolimus-eluting coronary stents has been associated with a nearly complete elimination of restenosis at 6 months and with a very low 1-year incidence of major adverse cardiac events (MACE). This analysis examined whether these beneficial effects persist over the longer term.
                This multicenter trial randomly assigned 238 patients to revascularization of single, de novo, native coronary artery lesions with sirolimus-eluting versus conventional bare-metal stents. Survival free from target lesion revascularization (TLR), target vessel failure (TVF), and MACE up to 3 years of follow-up was compared between the 2 treatment groups. Complete data sets were available in 94.2% of patients treated with sirolimus-eluting stents and in 94.1% of patients randomized to the control group. The cumulative 1-, 2-, and 3-year event-free survival rates were 99.2%, 96.5%, and 93.7% for TLR and 95.8%, 92.3%, and 87.9% for TVF, respectively, in the sirolimus-eluting stent group, versus 75.9%, 75.9%, and 75.0% for TLR and 71.2%, 69.4%, and 67.3% for TVF in the control group (P<0.001 for both comparisons at 3 years). Rates of MACE at 3 years were 15.8% in patients randomly assigned to sirolimus-eluting stents versus 33.1% in patients assigned to bare-metal stents (P=0.002). One patient treated with a sirolimus-eluting stent died of a cardiac cause between 12 and 36 months.
                Treatment of de novo coronary stenosis with sirolimus-eluting stents was associated with a sustained clinical benefit and very low rates of TLR and of other MACE up to 3 years after device implantation. 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.
                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.
                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. Sirolimus-eluting stents have been shown to decrease restenosis and reintervention as compared with standard stents. We evaluated the use of sirolimus-eluting stents in primary percutaneous coronary intervention for acute myocardial infarction with ST-segment elevation.
                We randomly assigned 120 patients to compare sirolimus-eluting stents with uncoated stents in primary percutaneous coronary intervention for acute myocardial infarction with ST-segment elevation. The primary end point was composite: death from cardiac causes, recurrent myocardial infarction, or target-lesion revascularization after 360 days.
                The rate of the primary end point was 6.7% in the sirolimus-eluting stent and 11% in the bare-metal stent group (relative risk 1.75, 95% CI 0.47-6.57, P = .402). The survival free from target-vessel failure showed a higher trend in the sirolimus-eluting stent group than in the bare-metal stent group (0.0% vs 5.7%, P = .064). There was no significant difference between the 2 groups in the rate of death (5% and 3.6%, respectively; P = .736), reinfarction (1.7% and 1.8%, respectively; P = .940), or stent thrombosis (3.4% and 1.8%, respectively; P = .621).
                Among selected patients with acute myocardial infarction and ST-segment elevation, the use of sirolimus-eluting stents shows a trend to reduce the rate of target-vessel revascularization in comparison with bare-metal stent. Restenosis after coronary stenting necessitates repeated percutaneous or surgical revascularization procedures. The delivery of paclitaxel to the site of vascular injury may reduce the incidence of neointimal hyperplasia and restenosis.
                At 73 U.S. centers, we enrolled 1314 patients who were receiving a stent in a single, previously untreated coronary-artery stenosis (vessel diameter, 2.5 to 3.75 mm; lesion length, 10 to 28 mm) in a prospective, randomized, double-blind study. A total of 652 patients were randomly assigned to receive a bare-metal stent, and 662 to receive an identical-appearing, slow-release, polymer-based, paclitaxel-eluting stent. Angiographic follow-up was prespecified at nine months in 732 patients.
                In terms of base-line characteristics, the two groups were well matched. Diabetes mellitus was present in 24.2 percent of patients; the mean reference-vessel diameter was 2.75 mm, and the mean lesion length was 13.4 mm. A mean of 1.08 stents (length, 21.8 mm) were implanted per patient. The rate of ischemia-driven target-vessel revascularization at nine months was reduced from 12.0 percent with the implantation of a bare-metal stent to 4.7 percent with the implantation of a paclitaxel-eluting stent (relative risk, 0.39; 95 percent confidence interval, 0.26 to 0.59; P<0.001). Target-lesion revascularization was required in 3.0 percent of the group that received a paclitaxel-eluting stent, as compared with 11.3 percent of the group that received a bare-metal stent (relative risk, 0.27; 95 percent confidence interval, 0.16 to 0.43; P<0.001). The rate of angiographic restenosis was reduced from 26.6 percent to 7.9 percent with the paclitaxel-eluting stent (relative risk, 0.30; 95 percent confidence interval, 0.19 to 0.46; P<0.001). The nine-month composite rates of death from cardiac causes or myocardial infarction (4.7 percent and 4.3 percent, respectively) and stent thrombosis (0.6 percent and 0.8 percent, respectively) were similar in the group that received a paclitaxel-eluting stent and the group that received a bare-metal stent.
                As compared with bare-metal stents, the slow-release, polymer-based, paclitaxel-eluting stent is safe and markedly reduces the rates of clinical and angiographic restenosis at nine months.
                Copyright 2004 Massachusetts Medical Society Compared with bare metal stents, drug-eluting stents reduce restenosis in noncomplex lesions. The utility of drug-eluting stents has not been evaluated in more difficult stenoses.
                To investigate the safety and efficacy of the polymer-based, slow-release paclitaxel-eluting stent in a patient population with more complex lesions than previously studied.
                Prospective, placebo-controlled, double-blind, multicenter randomized trial conducted from February 2003 to March 2004 at 66 academic and community-based institutions with 1156 patients who underwent stent implantation in a single coronary artery stenosis (vessel diameter, 2.25-4.0 mm; lesion length, 10-46 mm), including 664 patients (57.4%) with complex or previously unstudied lesions (requiring 2.25-mm, 4.0-mm, and/or multiple stents) and 9-month clinical and angiographic follow-up.
                Patients were randomly assigned to receive 1 or more bare metal stents (n = 579) or identical-appearing paclitaxel-eluting stents (n = 577).
                Ischemia-driven target vessel revascularization at 9 months.
                Baseline characteristics were well matched. Diabetes was present in 31% of patients. The mean (SD) reference vessel diameter was 2.69 (0.57) mm, the reference lesion length was 17.2 (9.2) mm, and 78% of lesions were type B2/C. A mean (SD) of 1.38 (0.58) stents (total mean [SD] length, 28.4 [13.1] mm) were implanted per lesion; 33% of lesions required multiple stents. Stents that were 2.25 mm and 4.0 mm in diameter were used in 18% and 17% of lesions, respectively. Compared with bare metal stents, paclitaxel-eluting stents reduced the 9-month rate of target lesion revascularization from 15.7% to 8.6% (P<.001) and target vessel revascularization from 17.3% to 12.1% (P = .02). Similar rates were observed for cardiac death or myocardial infarction (5.5% for bare metal stent group vs 5.7% for paclitaxel-eluting stent group) and stent thrombosis (0.7% in both groups). Angiographic restenosis was reduced from 33.9% to 18.9% in the entire study cohort (P<.001), including among patients receiving 2.25-mm stents (49.4% vs 31.2%; P = .01), 4.0-mm stents (14.4% vs 3.5%; P = .02), and multiple stents (57.8% vs 27.2%; P<.001).
                Compared with a bare metal stent, implantation of the paclitaxel-eluting stent in a patient population with complex lesions effectively reduces clinical and angiographic restenosis.
Drug-eluting stents releasing sirolimus, paclitaxel, dexamethasone and zotarolimus reduce composite cardiac events. However, this reduction is due largely to reductions in repeat revascularisation rates as there is no evidence of a significant effect on rates of death, MI or thrombosis. The increased cost of drug-eluting stents and lack of evidence of their cost-effectiveness means that various health funding agencies are having to limit or regulate their use in relation to price premium.