A clinical risk score for the prediction of very late stent thrombosis in drug eluting stent patients.

AIMS: Very late stent thrombosis (VLST; >1 year) is an infrequent but potentially serious complication, whose risk factors have not been fully elucidated. This investigation sought to develop a clinically useful risk stratification score for VLST following drug eluting stent (DES) placement. METHODS AND RESULTS: A Cox proportional hazards multivariate model of VLST was developed based on follow-up into a second year of patients enrolled in the ARRIVE registries, utilising readily available baseline clinical and angiographic characteristics. ST predictors between one and two years were identified among 7,459 consecutively enrolled patients who received a TAXUS® Express2™ (Boston Scientific, Natick, MA, USA) DES. Six significant predictors were found: presence of renal disease, prior myocardial infarction, multiple stenting, bifurcation lesions, prior CABG, and smoking at baseline. Each predictor was assigned a score, then summed for a maximum possible score of 10. Stratification into low and high risk groups revealed that VLST developed in 0.5% of 6,759 patients with scores<5, and 2.6% of 700 patients with scores≥5. CONCLUSIONS: We defined a VLST risk score for patients during the second year post DES-placement that provides a useful tool for risk stratification.

Drug-eluting stent thrombosis in routine clinical practice: two-year outcomes and predictors from the TAXUS ARRIVE registries.

BACKGROUND: Stent thrombosis (ST) is an uncommon but serious complication of drug-eluting and bare metal stents. To assess drug-eluting stent ST in contemporary practice, we analyzed 2-year data from the 7492-patient ARRIVE registry. METHODS AND RESULTS: Patients were enrolled at the initiation of percutaneous coronary intervention with no inclusion/exclusion criteria beyond use of the paclitaxel-eluting TAXUS stent. Two-year follow-up was 94% with independent adjudication of major cardiac events. A second, autonomous committee adjudicated Academic Research Consortium (ARC) definite/probable ST. Cumulative 2-year ARC-defined ST was 2.6% (1.0% early ST [<30 days], 0.7% late ST [31 to 365 days], and 0.8% very late ST [>1 year]). Simple-use (single-vessel and single-stent) cases had lower rates than expanded use (broader patient/lesion characteristics, 2-year cumulative: 1.4% versus 3.3%, P<0.001; early ST: 0.4% versus 1.4%, P<0.001; late ST: 0.5% versus 0.8%, P=0.14; very late ST: 0.4% versus 1.0%, P=0.008). Within 7 days of ST, 23% of patients died; 28% suffered Q-wave myocardial infarction. Mortality was higher with early ST (39%) than late ST (12%, P<0.001) or very late ST (13%, P<0.001). Multivariate analysis showed anatomic factors increased early ST (lesion >28 mm, lesion calcification) and late ST (vessel <3.0 mm); biological factors increased very late ST (renal disease, prior brachytherapy). Although early ST (71.4%) and very late ST (23.1%) patients had dual antiplatelet therapy at the time of ST, premature thienopyridine discontinuation was a strong independent predictor of both. CONCLUSIONS: The relative risks of early and late ST differ. Knowledge of ST risk for specific subgroups may guide revascularization options until the completion of randomized trials in these broad populations.

Expanded use of the TAXUS Express Stent: two-year safety insights from the 7,500 patient ARRIVE Registry programme.

AIMS: We report 2-year outcomes in a large unselected drug-eluting stent population (N=7,492) in the TAXUS Express2 ARRIVE post-market surveillance programme (101 U.S. sites). METHODS AND RESULTS: No specific inclusion/exclusion criteria were mandated; patients enrolled at procedure initiation. Two-year follow-up was 94%, with independent adjudication of major cardiac events, monitoring of patients with cardiac events and an additional 10-20% sample by site. Most ARRIVE cases (64%, n=4,794) typified expanded use based on patient/lesion characteristics outside the simple use (single vessel/stent) pivotal trial populations. These expanded use patients had higher 2-year rates than simple use patients for mortality (7.8% vs. 4.2%, P<0.001), myocardial infarction (MI, 3.9% vs. 2.2%, P<0.001), target lesion revascularisation (TLR, 9.2% vs. 5.4%, P<0.001), and stent thrombosis (3.3% vs. 1.4%, P<0.001). Among subgroups with renal disease, chronic total occlusion (CTO), lesion >28 mm, reference vessel diameter (RVD) <2.5 mm, multivessel stenting, acute MI, bifurcation, vein graft, or in-stent restenosis, TLR ranged from 3.8% to 8.9% in year one, and from 1.3% to 6.0% during year two. CONCLUSIONS: Mortality and stent-related events were higher in expanded use than simple use patients in the pivotal trials. ARRIVE provides a detailed estimate of procedural and 2-year outcomes in such real-world patients.

TAXUS VI final 5-year results: a multicentre, randomised trial comparing polymer-based moderate-release paclitaxel-eluting stent with a bare metal stent for treatment of long, complex coronary artery lesions.

AIMS: To assess the long-term safety and efficacy of the paclitaxel-eluting TAXUS moderate-release (MR) investigation-only stent for the treatment of long, complex coronary artery lesions. METHODS AND RESULTS: TAXUS VI was a prospective, double-blind, multicentre trial wherein 446 patients were randomised between a TAXUS Express MR stent and an uncoated Express Control stent. At 5-years, the overall rate of major adverse cardiac events (MACE) was similar in the two groups at 27.8% in control and 31.3% in TAXUS (P = 0.61), including similar rates for stent thrombosis. The target vessel revascularisation (TVR) rate was 23.7% in control and 22.2% in TAXUS (P = 0.45) with a non-target lesion revascularisation (non-TLR) rate of 5.1% in control and 10.9% in TAXUS (P = 0.0274) and a TLR rate of 21.4% in control and 14.6% in TAXUS (relative reduction, 32%; P = 0.0325). Furthermore, subgroup analysis revealed that the TLR benefit of TAXUS was preserved among study groups including small vessels, long lesions and patients receiving multiple overlapping stents. CONCLUSIONS: Treatment of complex coronary lesions with the TAXUS MR stent demonstrated similar MACE, similar TVR, and reduced TLR rates compared with control through five years. Based on these positive results, the aetiology of increased non-TLR TVR rate in TAXUS remains unclear.

One-year outcomes with the Taxus Liberté stent in the real world: the Taxus Olympia registry (phase I).

BACKGROUND: The Taxus Olympia registry is a prospective, postapproval registry collecting clinical outcomes data on patients receiving the Taxus Liberté paclitaxel-eluting stent during routine interventional cardiology practice. METHODS: Between February and July 2005, 529 patients receiving the Taxus Liberté stent at 16 centers in the Middle East, South/Central America, and Asia/Pacific regions were enrolled in Phase I of Olympia. The primary end-point was Taxus Liberté stent-related cardiac events (cardiac death, MI, and revascularization) at 30 days postimplant. Additional clinical assessment was conducted at 6 and 12 months. Olympia phases II and III are in clinical follow-up and will be reported separately. RESULTS: One-year clinical follow-up is available for 98% of patients. Complex patients and lesions were prevalent, including: 50% diabetes mellitus, 49% multivessel disease, 30% multiple stenting, 48% AHA/ACC type B2/C lesions, 19% long lesions (>26 mm), and 40% small vessels (30 days postprocedure. One-year cardiac event rates among complex subpopulations (diabetics 5.0%, multiple stents 3.8%, long lesions 3.1%, and small vessels 2.9%) were comparable to the overall study population. CONCLUSIONS: In conclusion, this first report of real-world experience with the Taxus Liberté stent demonstrates the safety and clinical utility of this stent in the broader spectrum of coronary disease treated in everyday practice.

A clinical risk score for prediction of stent thrombosis.

The aim was to develop a clinically useful patient risk score predictive for stent thrombosis (ST). Using readily available baseline clinical and angiographic characteristics, a Cox proportional hazards multivariate model was used to identify significant (p <0.10) predictors of ST through 1 year in 2,487 patients receiving a TAXUS Express (Boston Scientific Corp., Natick, Massachusetts) drug-eluting stent (DES) in the ARRIVE 1 registry. Hazard ratios of significant predictors were rounded to an integer value ranging from 2 to 5. These values were summed for a maximum possible score of 24. The model was validated using 1-year data from a similar DES data set (ARRIVE 2, n = 4,820 patients). The 8 significant predictors found were thienopyridine therapy discontinuation before 6 months, insulin-requiring diabetes, smoker at baseline, left main stent placement, multiple stent placement, lesion length >28 mm, moderate to severe lesion calcification, and reference vessel diameter <3 mm. Model discrimination was high, indicated by an area under the receiver-operator characteristic curve of 0.819. Stratification of patients into low-, medium-, and high-risk groups showed that ST developed in 0.8% of patients with a score <6, 3.6% of patients with a score of 7 to 13, and 12.6% of patients with a score >or=14. In conclusion, using 8 readily available clinical and angiographic characteristics, we defined an ST risk score for patients receiving a DES during the first year. Analysis of patients from ARRIVE 1 and 2 showed that most (73%) were in the lowest risk category, with 25% in the moderate risk category. Less than 2% were at highest risk of developing ST.

Off-label use: an industry perspective on expanding use beyond approved indications.

The use of a medical device outside of its approved label is commonly referred to as "off-label use." Off-label use arises when physicians see the opportunity to leverage an approved therapy for an unmet patient need. This practice typically occurs on a case by case basis without clear documentation of indication, frequency, or outcomes. Sponsors have a responsibility to consider formal indication expansion depending on the actual use, how well the therapy fits the unmet need, product iteration cycles, adoption speed, resource demands, and the clinical risk to benefit ratio. This responsibility is particularly relevant for breakthrough technologies where adoption patterns can span a variety of uses. For Boston Scientific's drug-eluting stent program, a surveillance program was developed in collaboration with the FDA to compile information on practice patterns and safety outcomes for the TAXUS Express2 Paclitaxel-Eluting Coronary Stent System. The ARRIVE program has used a Web-based format to collect real-time data on TAXUS stent use. This >7,000 patient registry documents both on-label and off-label use and key safety measures for the TAXUS stent. This real-world registry has successfully provided a data-driven approach to BSC's product development strategy, including the initiation of formal label expansion programs. For complex or combination products, more innovative ways of capturing risk to benefit data are needed to define off-label use and to maximize the potential therapeutic utility as supported by safety data.