An optical coherence tomography study of a biodegradable vs. durable polymer-coated limus-eluting stent: a LEADERS trial sub-study

Incomplete endothelialization has been found to be associated with late stent thrombosis, a rare but devastating phenomenon, more frequent after drug-eluting stent implantation. Optical coherence tomography (OCT) has 10 times greater resolution than intravascular ultrasound and thus appears to be a valuable modality for the assessment of stent strut coverage. The LEADERS trial was a multi-centre, randomized comparison of a biolimus-eluting stent (BES) with biodegradable polymer with a sirolimus-eluting stent (SES) using a durable polymer. This study sought to evaluate tissue coverage and apposition of stents using OCT in a group of patients from the randomized LEADERS trial.

The twelve-month outcomes of a biolimus eluting stent with a biodegradable polymer compared with a sirolimus eluting stent with a durable polymer

This study reports the 12-month clinical outcomes of the LEADERS clinical trial which compared a biolimus eluting stent with a biodegradable polymer (BES) to a sirolimus eluting stent with a durable polymer (SES).

Value of the SYNTAX score for risk assessment in the all-comers population of the randomized multicenter LEADERS (Limus Eluted from A Durable versus ERodable Stent coating) trial

OBJECTIVES: We aimed to assess the predictive value of the SYNTAX score (SXscore) for major adverse cardiac events in the all-comers population of the LEADERS (Limus Eluted from A Durable versus ERodable Stent coating) trial. BACKGROUND: The SXscore has been shown to be an effective predictor of clinical outcomes in patients with multivessel disease undergoing percutaneous coronary intervention. METHODS: The SXscore was prospectively collected in 1,397 of the 1,707 patients enrolled in the LEADERS trial (patients after surgical revascularization were excluded). Post hoc analysis was performed by stratifying clinical outcomes at 1-year follow-up, according to 1 of 3 SXscore tertiles. RESULTS: The 1,397 patients were divided into tertiles based on the SXscore in the following fashion: SXscore8 and 16 (SXhigh) (n=461). At 1-year follow-up, there was a significantly lower number of patients with major cardiac event-free survival in the highest tertile of SXscore (SXlow=92.2%, SXmid=91.1%, and SXhigh=84.6%; p<0.001). Death occurred in 1.5% of SXlow patients, 2.1% of SXmid patients, and 5.6% of SXhigh patients (hazard ratio [HR]: 1.97, 95% confidence interval [CI]: 1.29 to 3.01; p=0.002). The myocardial infarction rate tended to be higher in the SXhigh group. Target vessel revascularization was 11.3% in the SXhigh group compared with 6.3% and 7.8% in the SXlow and SXmid groups, respectively (HR: 1.38, 95% CI: 1.1 to 1.75; p=0.006). Composite of cardiac death, myocardial infarction, and clinically indicated target vessel revascularization was 7.8%, 8.9%, and 15.4% in the SXlow, SXmid, and SXhigh groups, respectively (HR: 1.47, 95% CI: 1.19 to 1.81; p<0.001). CONCLUSIONS: The SXscore, when applied to an all-comers patient population treated with drug-eluting stents, may allow prospective risk stratification of patients undergoing percutaneous coronary intervention. (LEADERS Trial Limus Eluted From A Durable Versus ERodable Stent Coating; NCT00389220).

The outcome of bifurcation lesion stenting using a biolimus-eluting stent with a bio-degradable polymer compared to a sirolimus-eluting stent with a durable polymer

This study investigated the differences in clinical outcomes between patients with bifurcation lesions (BL) treated with a biolimus-eluting stent (BES) with a biodegradable polymer, and a sirolimus-eluting stent (SES) with a durable polymer.

A "Beyond WTO" Scenario for Swiss Agriculture: Consequences for Income Generation and the Provision of Public Goods

The conclusion of the Doha Round negotiations is likely to influence Swiss agricultural policy substantially. The same goes for a free trade agreement in agriculture and food with the European Communities. Even though neither of them will bring about duty-free and quota-free market access, or restrict domestic support measures to green box compatible support, both would represent a big step in that direction. There is no empirical evidence on the effect of such a counterfactual scenario for Swiss agriculture. We therefore use a normative mathematical programming model to illustrate possible effects for agricultural production and the corresponding agricultural income. Moreover, we discuss the results with respect to the provision of public goods under the assumption of continuing green box-compatible direct payments. The aim of our article is to bring more transparency into the discussion on the effects of freer and less distorted trade on the income generation by a multifunctional agriculture. The article will be organized as follows. In the first Section we specify the background of our study. In the second section, we focus on the problem statement and our research questions. In Section 3, we describe in detail a counterfactual scenario of “duty-free, quota-free and price support-free” agriculture from an economic as well as a legal perspective. Our methodology and the results are presented in Section 4 and 5 respectively. In Section 6, we discuss our results with respect to economic and legal aspects of multifunctional agriculture.

Long-term clinical outcomes of biodegradable polymer biolimus-eluting stents versus durable polymer sirolimus-eluting stents in patients with coronary artery disease (LEADERS): 4 year follow-up of a randomised non-inferiority trial

Background The effectiveness of durable polymer drug-eluting stents comes at the expense of delayed arterial healing and subsequent late adverse events such as stent thrombosis (ST). We report the 4 year follow-up of an assessment of biodegradable polymer-based drug-eluting stents, which aim to improve safety by avoiding the persistent inflammatory stimulus of durable polymers. Methods We did a multicentre, assessor-masked, non-inferiority trial. Between Nov 27, 2006, and May 18, 2007, patients aged 18 years or older with coronary artery disease were randomly allocated with a computer-generated sequence to receive either biodegradable polymer biolimus-eluting stents (BES) or durable polymer sirolimus-eluting stents (SES; 1:1 ratio). The primary endpoint was a composite of cardiac death, myocardial infarction, or clinically-indicated target vessel revascularisation (TVR); patients were followed-up for 4 years. Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00389220. Findings 1707 patients with 2472 lesions were randomly allocated to receive either biodegradable polymer BES (857 patients, 1257 lesions) or durable polymer SES (850 patients, 1215 lesions). At 4 years, biodegradable polymer BES were non-inferior to durable polymer SES for the primary endpoint: 160 (18·7%) patients versus 192 (22·6%) patients (rate ratios [RR] 0·81, 95% CI 0·66–1·00, p for non-inferiority <0·0001, p for superiority=0·050). The RR of definite ST was 0·62 (0·35–1·08, p=0·09), which was largely attributable to a lower risk of very late definite ST between years 1 and 4 in the BES group than in the SES group (RR 0·20, 95% CI 0·06–0·67, p=0·004). Conversely, the RR of definite ST during the first year was 0·99 (0·51–1·95; p=0·98) and the test for interaction between RR of definite ST and time was positive (pinteraction=0·017). We recorded an interaction with time for events associated with ST but not for other events. For primary endpoint events associated with ST, the RR was 0·86 (0·41–1·80) during the first year and 0·17 (0·04–0·78) during subsequent years (pinteraction=0·049). Interpretation Biodegradable polymer BES are non-inferior to durable polymer SES and, by reducing the risk of cardiac events associated with very late ST, might improve long-term clinical outcomes for up to 4 years compared with durable polymer SES. Funding Biosensors Europe SA, Switzerland.

Two-year clinical follow-up from the randomized comparison of biolimus-eluting stents with biodegradable polymer and sirolimus-eluting stents with durable polymer in routine clinical practice

Objectives This study sought to investigate safety and efficacy of biolimus-eluting stents (BES) with biodegradable polymer as compared with sirolimus-eluting stents (SES) with durable polymer through 2 years of follow-up. Background BES with a biodegradable polymer provide similar efficacy and safety as SES with a durable polymer at 9 months. Clinical outcomes beyond the period of biodegradation of the polymer used for drug release and after discontinuation of dual antiplatelet therapy are of particular interest. Methods A total of 1,707 patients were randomized to unrestricted use of BES (n = 857) or SES (n = 850) in an all-comers patient population. Results At 2 years, BES remained noninferior compared with SES for the primary endpoint, which was a composite of cardiac death, myocardial infarction, or clinically indicated target vessel revascularization (BES 12.8% vs. SES 15.2%, hazard ratio [HR]: 0.84, 95% confidence interval [CI]: 0.65 to 1.08, pnoninferiority < 0.0001, psuperiority = 0.18). Rates of cardiac death (3.2% vs. 3.9%, HR: 0.81, 95% CI: 0.49 to 1.35, p = 0.42), myocardial infarction (6.3% vs. 5.6%, HR: 1.12, 95% CI: 0.76 to 1.65, p = 0.56), and clinically indicated target vessel revascularization (7.5% vs. 8.6%, HR: 0.86, 95% CI: 0.62 to 1.20, p = 0.38) were similar for BES and SES. The rate of definite stent thrombosis through 2 years was 2.2% for BES and 2.5% for SES (p = 0.73). For the period between 1 and 2 years, event rates for definite stent thrombosis were 0.2% for BES and 0.5% for SES (p = 0.42). After discontinuation of dual antiplatelet therapy, no very late definite stent thrombosis occurred in the BES group. Conclusions At 2 years of follow-up, the unrestricted use of BES with a biodegradable polymer maintained a similar safety and efficacy profile as SES with a durable polymer. (Limus Eluted From a Durable Versus Erodable Stent Coating [LEADERS]; NCT00389220)

Biolimus-eluting stent with biodegradable polymer versus sirolimus-eluting stent with durable polymer for coronary revascularisation (LEADERS): a randomised non-inferiority trial

BACKGROUND: A novel stent platform eluting biolimus, a sirolimus analogue, from a biodegradable polymer showed promising results in preliminary studies. We compared the safety and efficacy of a biolimus-eluting stent (with biodegradable polymer) with a sirolimus-eluting stent (with durable polymer). METHODS: We undertook a multicentre, assessor-blind, non-inferiority study in ten European centres. 1707 patients aged 18 years or older with chronic stable coronary artery disease or acute coronary syndromes were centrally randomised by a computer-generated allocation sequence to treatment with either biolimus-eluting (n=857) or sirolimus-eluting (n=850) stents. The primary endpoint was a composite of cardiac death, myocardial infarction, or clinically-indicated target vessel revascularisation within 9 months. Analysis was by intention to treat. 427 patients were randomly allocated to angiographic follow-up, with in-stent percentage diameter stenosis as principal outcome measure at 9 months. The trial is registered with ClinicalTrials.gov, number NCT00389220. FINDINGS: We analysed all randomised patients. Biolimus-eluting stents were non-inferior to sirolimus-eluting stents for the primary endpoint at 9 months (79 [9%] patients vs 89 [11%], rate ratio 0.88 [95% CI 0.64-1.19], p for non-inferiority=0.003, p for superiority=0.39). Frequency of cardiac death (14 [1.6%] vs 21 [2.5%], p for superiority=0.22), myocardial infarction (49 [5.7%] vs 39 [4.6%], p=0.30), and clinically-indicated target vessel revascularisation (38 [4.4%] vs 47 [5.5%], p=0.29) were similar for both stent types. 168 (79%) patients in the biolimus-eluting group and 167 (78%) in the sirolimus-eluting group had data for angiographic follow-up available. Biolimus-eluting stents were non-inferior to sirolimus-eluting stents in in-stent percentage diameter stenosis (20.9%vs 23.3%, difference -2.2% [95% CI -6.0 to 1.6], p for non-inferiority=0.001, p for superiority=0.26). INTERPRETATION: Our results suggest that a stent eluting biolimus from a biodegradable polymer represents a safe and effective alternative to a stent eluting sirolimus from a durable polymer in patients with chronic stable coronary artery disease or acute coronary syndromes. FUNDING: Biosensors Europe SA, Switzerland.