Sirolimus-Eluting Stents at Two Years: A Pooled Analysis of SIRIUS, E-SIRIUS, and C-SIRIUS With Emphasis on Late Revascularizations and Stent Thromboses

Schampaert, Erick; Moses, Jeffrey W.; Schofer, Joachim; Schlüter, Michael; Gershlick, Anthony; Cohen, Éric A.; Palisaitis, Donald; Breithardt, Günter; Donohoe, Dennis; Wang, Hong; Popma, Jeffrey J.; Kuntz, Richard E.; Leon, Martin B.

doi:10.1016/j.amjcard.2006.01.049

Cited by 79 publications

(33 citation statements)

References 20 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…This contrasts with observations in porcine models, in which the initial benefits of DES are reported to disappear with time, 18 but mirrors long-term findings of the first DES trials 15,16,19 and the 2-year results of the RESEARCH registry. 11 As evident in Figure 1, the advantage of DES over BMS is largely obtained during the first year and then maintained without apparent loss of efficacy over time; however, the 46% reduction of target-lesion revascularization and the 32% reduction of TVR does not appear as striking as reported in clinical trials.…”

Section: Discussioncontrasting

confidence: 53%

Long-Term Safety and Efficacy of Drug-Eluting Stents

et al. 2007

View full text Add to dashboard Cite

Background-The long-term safety and efficacy of drug-eluting stents (DES) have been questioned recently. Methods and Results-Between July 2002 and June 2005, 10 629 patients undergoing elective percutaneous coronary intervention with either DES (nϭ3064) or bare-metal stents (BMS, nϭ7565) were enrolled in a prospective registry comprising 13 hospitals. We assessed the cumulative incidence of major adverse cardiac events (death, acute myocardial infarction, and target-vessel revascularization) and angiographic stent thrombosis during 2-year follow-up. A propensity score analysis to adjust for different baseline clinical, angiographic, and procedural characteristics was performed. The 2-year unadjusted cumulative incidence of major adverse cardiac events was 17.8% in the DES group and 21.0% in the BMS group (Pϭ0.003 by log-rank test). Angiographic stent thrombosis was 1.0% in the DES group and 0.6% in the BMS group (Pϭ0.09). After adjustment, the 2-year cumulative incidence of death was 6.8% in the DES group and 7.4% in the BMS group (Pϭ0.35), whereas the rates were 5.3% in DES and 5.8% in BMS for acute myocardial infarction (Pϭ0.46), 9.1% in DES and 12.9% in BMS for target-vessel revascularization (PϽ0.00001), and 16.9% in DES and 21.8% in BMS for major adverse cardiac events (PϽ0.0001). Independent predictors of target-vessel revascularization in the DES group were diabetes mellitus (hazard ratio 1.36, 95% confidence interval 1.06 to 1.76), renal failure (hazard ratio 1.69, 95% confidence interval 1.06 to 2.69), and reference vessel diameter (hazard ratio 0.64, 95% confidence interval 0.45 to 0.93). Conclusions-In

show abstract

Section: Discussioncontrasting

confidence: 53%

Long-Term Safety and Efficacy of Drug-Eluting Stents

et al. 2007

View full text Add to dashboard Cite

show abstract

“…(4) The risk of ST after discontinuation of thienopyridine treatment after 6 months, if present, appears to be small. A cumulative 1.9% incidence of ST at 18 months is higher than that reported in the major randomized trials [25][26][27] or in large registries such as e-Cypher. 16 However, considering the longer follow-up, the rate of ST in the present study is comparable to other studies analyzing "real-world" populations.…”

Section: Discussionmentioning

confidence: 63%

“…This calls into question the temporal and causal link between discontinuation and thrombosis after 6 months, and this finding is in agreement with a recent small study. 29 In many pivotal studies and in some registries, 16,26 the relationship between discontinuation of clopidogrel and development of late ST is not clear. We prefer not to speculate about possible mechanisms for ST that occurs after 6 months or about the benefits of extended dual-antiplatelet therapy.…”

Section: Discussionmentioning

confidence: 99%

Incidence and Predictors of Drug-Eluting Stent Thrombosis During and After Discontinuation of Thienopyridine Treatment

et al. 2007

View full text Add to dashboard Cite

Background-The need for prolonged aspirin and thienopyridine therapy and the risk of stent thrombosis (ST) remain as drawbacks associated with drug-eluting stents. Methods and Results-A prospective observational cohort study was conducted between June 2002 and January 2004 on 3021 patients consecutively and successfully treated in 5389 lesions with drug-eluting stents. Detailed patient information was collected on antiplatelet therapy. We analyzed the incidence of ST throughout the 18-month follow-up period and its relationship with thienopyridine therapy. ST occurred in 58 patients (1.9%) at 18 months. Forty-two patients (1.4%) experienced the event within 6 months of stent implantation. Acute myocardial infarction (fatal or nonfatal) occurred in 46 patients (79%) and death in 23 patients (39%) with ST. The median interval from discontinuation of thienopyridine therapy to ST was 13.5 days (interquartile range 5.2 to 25.7 days) for the first 6 months and 90 days (interquartile range 30 to 365 days) between 6 and 18 months. On multivariable analysis, the strongest predictor for ST within 6 months of stenting was discontinuation of thienopyridine therapy (hazard ratio, 13.74; 95% CI, 4.04 to 46.68; PϽ0.001). Thienopyridine discontinuation after 6 months did not predict the occurrence of ST (hazard ratio, 0.94; 95% CI, 0.30 to 2.98; Pϭ0.92). Conclusions-Discontinuation of thienopyridine therapy was the major determinant of ST within the first 6 months, but insufficient information is available to determine whether there is benefit in continuing a thienopyridine beyond 6 months. (Circulation. 2007;116:745-754.)

show abstract

“…7,8 Follow-up data from SIRIUS, and other recent trials appeared to alleviate these concerns. 9,10 Since the presentation of these findings, however, the concerns regarding these agents enhancing in stent thrombosis resurfaced. An observational study demonstrated a 30% incidence of in stent thrombosis associated with DES and clopidogrel noncompliance.…”

mentioning

confidence: 99%

Antiproliferative Agents Alter Vascular Plasminogen Activator Inhibitor-1 Expression

Muldowney

Stringham

Levy

et al. 2007

ATVB

View full text Add to dashboard Cite

Objectives-Drug eluting stents (DES) reduce the incidence of restenosis after coronary angioplasty. Enthusiasm has been tempered by a possible increased risk of in-stent thrombosis. We examined the effects of paclitaxel and rapamycin on the endothelial transcriptome to identify alterations in gene expression associated with thrombosis. Methods and Results-Gene expression profiling was performed on human coronary artery endothelial cells treated with rapamycin or paclitaxel. Plasminogen activator inhibitor-1 (PAI-1) was the most consistently induced transcript in rapamycin-treated human coronary artery endothelial cells. RT-PCR and ELISA were performed to confirm positive findings. Transgenic mice engineered to express enhanced green fluorescent protein under control of the human PAI-1 promoter were also treated. Rapamycin and paclitaxel treated endothelial cells produced dose-dependent increases in PAI-1. There was a variable effect on endothelial tissue-type plasminogen activator (t-PA) expression. Enhanced expression of PAI-1 and enhanced green fluorescent protein were detected in coronary arteries, the aorta, and kidney of the mice. Key Words: antiproliferative Ⅲ plasminogen activator inhibitor 1 Ⅲ rapamycin paclitaxel gene array Ⅲ endothelial cells Ⅲ gene expression R estenosis is widely recognized as a major factor limiting the long-term clinical efficacy of percutaneous coronary intervention. 1 The 30% to 50% incidence of restenosis associated with balloon angioplasty alone has been reduced in half by the use of bare metal stents. 2 Numerous mechanical and pharmacological strategies have failed to further reduce restenosis until recently. 3,4 The development of drug eluting stents (DES) that release small amounts of antiproliferative agents locally provides an effective strategy for reducing the risk of restenosis after angioplasty to levels below 10%. 5,6 These impressive effects on restenosis were tempered initially by concerns about possible increases in the rate of in stent thrombosis with DES. 7,8 Follow-up data from SIRIUS, and other recent trials appeared to alleviate these concerns. 9,10 Conclusion-Antiproliferative

show abstract

Sirolimus-Eluting Stents at Two Years: A Pooled Analysis of SIRIUS, E-SIRIUS, and C-SIRIUS With Emphasis on Late Revascularizations and Stent Thromboses

Cited by 79 publications

References 20 publications

Long-Term Safety and Efficacy of Drug-Eluting Stents

Long-Term Safety and Efficacy of Drug-Eluting Stents

Incidence and Predictors of Drug-Eluting Stent Thrombosis During and After Discontinuation of Thienopyridine Treatment

Antiproliferative Agents Alter Vascular Plasminogen Activator Inhibitor-1 Expression

Contact Info

Product

Resources

About