http://repub.eur.nl/res/aut/17145/ List of Publications en http://repub.eur.nl/static-eur/img/logo.png http://repub.eur.nl http://repub.eur.nl/res/pub/20963/ 2010-07-20T00:00:00Z 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: SXscore ≤8 (SXlow) (n = 464), SXscore >8 and ≤16 (SXmid) (n = 472), and SXscore >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) http://repub.eur.nl/res/pub/20630/ 2010-07-01T00:00:00Z BACKGROUND: New-generation coronary stents that release zotarolimus or everolimus have been shown to reduce the risk of restenosis. However, it is unclear whether there are differences in efficacy and safety between the two types of stents on the basis of prospectively adjudicated end points endorsed by the Food and Drug Administration. METHODS: In this multicenter, noninferiority trial with minimal exclusion criteria, we randomly assigned 2292 patients to undergo treatment with coronary stents releasing either zotarolimus or everolimus. Twenty percent of patients were randomly selected for repeat angiography at 13 months. The primary end point was target-lesion failure, defined as a composite of death from cardiac causes, any myocardial infarction (not clearly attributable to a nontarget vessel), or clinically indicated target-lesion revascularization within 12 months. The secondary angiographic end point was the extent of in-stent stenosis at 13 months. RESULTS: At least one off-label criterion for stent placement was present in 66% of patients. The zotarolimus-eluting stent was noninferior to the everolimus-eluting stent with respect to the primary end point, which occurred in 8.2% and 8.3% of patients, respectively (P<0.001 for noninferiority). There were no significant between-group differences in the rate of death from cardiac causes, any myocardial infarction, or revascularization. The rate of stent thrombosis was 2.3% in the zotarolimus-stent group and 1.5% in the everolimus-stent group (P = 0.17). The zotarolimus-eluting stent was also noninferior regarding the degree (±SD) of in-stent stenosis (21.65±14.42% for zotarolimus vs. 19.76±14.64% for everolimus, P = 0.04 for noninferiority). In-stent late lumen loss was 0.27±0.43 mm in the zotarolimus-stent group versus 0.19±0.40 mm in the everolimusstent group (P = 0.08). There were no significant between-group differences in the rate of adverse events. CONCLUSIONS: At 13 months, the new-generation zotarolimus-eluting stent was found to be noninferior to the everolimus-eluting stent in a population of patients who had minimal exclusion criteria. http://repub.eur.nl/res/pub/18221/ 2010-02-15T00:00:00Z The aim of this analysis was to assess the effect of body mass index (BMI) on 1-year outcomes in patients enrolled in a contemporary percutaneous coronary intervention trial comparing a sirolimus-eluting stent with a durable polymer to a biolimus-eluting stent with a biodegradable polymer. A total of 1,707 patients who underwent percutaneous coronary intervention were randomized to treatment with either biolimus-eluting stents (n = 857) or sirolimus-eluting stents (n = 850). Patients were assigned to 1 of 3 groups according to BMI: normal (<25 kg/m(2)), overweight (25 to 30 kg/m(2)), or obese (>30 kg/m(2)). At 1 year, the incidence of the composite of cardiac death, myocardial infarction, and clinically justified target vessel revascularization was assessed. In addition, rates of clinically justified target lesion revascularization and stent thrombosis were assessed. Cox proportional-hazards analysis, adjusted for clinical differences, was used to develop models for 1-year mortality. Forty-five percent of the patients (n = 770) were overweight, 26% (n = 434) were obese, and 29% (n = 497) had normal BMIs. At 1-year follow-up, the cumulative rate of cardiac death, myocardial infarction, and clinically justified target vessel revascularization was significantly higher in the obese group (8.7% in normal-weight, 11.3% in overweight, and 14.5% in obese patients, p = 0.01). BMI (hazard ratio 1.47, 95% confidence interval 1.02 to 2.14, p = 0.04) was an independent predictor of stent thrombosis. Stent type had no impact on the composite of cardiac death, myocardial infarction, and clinically justified target vessel revascularization at 1 year in the 3 BMI groups (hazard ratio 1.08, 95% confidence interval 0.63 to 1.83, p = 0.73). In conclusion, BMI was an independent predictor of major adverse cardiac events at 1-year clinical follow-up. The higher incidence of stent thrombosis in the obese group may suggest the need for a weight-adjusted dose of clopidogrel. http://repub.eur.nl/res/pub/27668/ 2010-02-01T00:00:00Z Background: Animal models show impairment of arterial healing after drug-eluting stents (DES) compared with bare-metal stents (BMS). Virtual histology intravascular ultrasound (VH-IVUS) offers an opportunity to assess lesion morphology in vivo. Methods: We used VH-IVUS in 80 patients to assess long-term (median = 10 months) native artery vascular responses after 76 implantations of DES compared with 32 BMS. The presence of "necrotic core abutting the lumen" was evaluated at baseline and follow-up. Results: At baseline, necrotic core abutting the lumen through the stent struts was observed in 76% of DES and 75% of BMS. Although the percentage of necrotic core within the plaque behind the stents did not change during follow-up in DES (23% [18%, 28%] to 22% [17%, 27%], P = .57) or BMS (22% [19%, 27%] to 20% [12%, 26%], P = .29), necrotic core abutting the lumen through the stent struts decreased more in BMS (75% to 19%, P < .001) than DES (76% to 61%, P = .036) because of the lack of an overlying, protective neointima in DES-treated lesions. Furthermore, within the adjacent reference segments, the incidence of necrotic core abutting the lumen decreased in BMS-treated lesions (proximal 23% to 0%, P = .023; distal 21% to 0%, P = .023), but not in DES (proximal 22% to 17%, P = .48; distal 23% to 21%, P = .82). Conclusions: Serial VH-IVUS analysis of DES-treated lesions showed a greater frequency of unstable lesion morphometry at follow-up compared with BMS. The apparent mechanism was a suppression of the protective neointimal hyperplasia layer coupled with a lack of vulnerable plaque resolution at reference segments in DES compared with BMS. http://repub.eur.nl/res/pub/14726/ 2008-09-01T00:00:00Z 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.