http://repub.eur.nl/res/aut/7479/ List of Publications en http://repub.eur.nl/static-eur/img/logo.png http://repub.eur.nl http://repub.eur.nl/res/pub/34687/ 2011-02-01T00:00:00Z Background-The age, creatinine, and ejection fraction (ACEF) score (age/left ventricular ejection fraction+1 if creatinine >2.0 mg/dL) has been established as an effective predictor of clinical outcomes in patients undergoing elective coronary artery bypass surgery; however, its utility in "all-comer" patients undergoing percutaneous coronary intervention is yet unexplored. Methods and Results-The ACEF score was calculated for 1208 of the 1707 patients enrolled in the LEADERS trial. Post hoc analysis was performed by stratifying clinical outcomes at the 1-year follow-up according to ACEF score tertiles: ACEFlow≤1.0225, 1.0225< ACEFmid≤1.277, and ACEFhigh>1.277. At 1-year follow-up, there was a significantly lower number of patients with major adverse cardiac event-free survival in the highest tertile of the ACEF score (ACEFlow=92.1%, ACEFmid=89.5%, and ACEFhigh=86.1%; P=0.0218). Cardiac death was less frequent in ACEFlowthan in ACEFmidand ACEFhigh(0.7% vs 2.2% vs 4.5%; hazard ratio=2.22, P=0.002) patients. Rates of myocardial infarction were significantly higher in patients with a high ACEF score (6.7% for ACEFhighvs 5.2% for ACEFmidand 2.5% for ACEFlow; hazard ratio=1.6, P=0.006). Clinically driven target-vessel revascularization also tended to be higher in the ACEFhighgroup, but the difference among the 3 groups did not reach statistical significance. The rate of composite definite, possible, and probable stent thrombosis was also higher in the ACEFhighgroup (ACEFlow=1.2%, ACEFmid=3.5%, and ACEFhigh=6.2%; hazard ratio=2.04, P=0.001). Conclusions-ACEF score may be a simple way to stratify risk of events in patients treated with percutaneous coronary intervention with respect to mortality and risk of myocardial infarction. http://repub.eur.nl/res/pub/28527/ 2010-05-01T00:00:00Z Objectives: To reassess the reproducibility of the SYNTAX score. Background: The SYNTAX score appears to have an important role to play in the evaluation of patients with complex coronary artery disease undergoing revascularisation. However, the calculation of the SYNTAX score relies on the subjective assessment of lesions using coronary angiography, and therefore is subject to intra-and inter-observer variability. Methods: The SYNTAX score was calculated in 100 patients randomly selected from the SYNTAX trial, on two occasions 8 weeks apart, by a team made up of three interventional cardiologists. The weighted kappa values were compared with values obtained 1 year previously, when core lab analysts assessed the intra-observer reproducibility amongst the same patient cohort. Results: The mean ± standard deviation difference in SYNTAX score was 2.1 ± 7.6. The respective weighted kappa values for the number of lesions, bifurcation lesions, ostial lesions, and total occlusions were 0.62, 0.36, 0.66, and 0.91 compared with 0.59, 0.41, 0.63, and 0.82 in the previous core lab assessment. The weighted kappa for the intra-observer reproducibility of the SYNTAX score grouped into deciles was 0.54, and according to the terciles ≤22, >22-≤32, >32 was 0.51 both indicating a moderate level of agreement beyond the level of chance. In the previous assessment, the comparative kappa values were 0.45 and 0.53. Conclusions: The SYNTAX score has moderate intra-observer reproducibility when assessed by a team of three interventional cardiologists, which is consistent with a prior evaluation performed by core lab analysts. The scoring of bifurcation lesions remains the main source of inconsistency. 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/27783/ 2010-01-08T00:00:00Z Background: Everolimus-eluting and paclitaxel-eluting stents, compared with bare metal stents, reduced the risk of restenosis in clinical trials with strict inclusion and exclusion criteria. We compared the safety and efficacy of the second-generation everolimus-eluting and paclitaxel-eluting stents in real-life practice. Methods: We randomly assigned 1800 consecutive patients (aged 18-85 years) undergoing percutaneous coronary intervention at one centre to treatment with everolimus-eluting or paclitaxel-eluting stents. The primary endpoint was a composite of safety and efficacy (all-cause mortality, myocardial infarction, and target vessel revascularisation) within 12 months. Patients were not told which stent they had been allocated. Analysis was by intention to treat. The trial is registered with ClinicalTrials.gov, number NCT01016041. Findings: Follow-up was completed in 1797 patients. The primary endpoint occurred in 56 (6%) of 897 patients in the everolimus-eluting stent group versus 82 (9%) of 903 in the paclitaxel-eluting stent group (relative risk 0·69 [95% CI 0·50-0·95], p value for superiority=0·02). The difference was attributable to a lower rate of stent thrombosis (6 [<1%] vs 23 [3%], 0·26 [0·11-0-64], p=0·002), myocardial infarction (25 [3%] vs 48 [5%], 0·52 [0·33-0·84], p=0·007), and target vessel revascularisation (21 [2%] vs 54 [6%], 0·39 [0·24-0·64], p=0·0001). Cardiac death, non-fatal myocardial infarction, or target lesion revascularisation occurred in 44 [5%] patients in the everolimus-eluting stent group versus 74 [8%] patients in the paclitaxel-eluting stent group, p value for superiority was 0·005. Interpretation: The everolimus-eluting stent is better than the second generation paclitaxel-eluting stent in unselected patients in terms of safety and efficacy. On the basis of our results, we suggest that paclitaxel-eluting stents should no longer be used in everyday clinical practice. Funding: Unrestricted grants from Abbott Vascular and Boston Scientific. http://repub.eur.nl/res/pub/24893/ 2009-07-01T00:00:00Z Objective: The The Arterial Revascularization Therapies Study (ARTS)-II trial found no differences in survival or overall adverse events between sirolimus-eluting stents (SES) and the surgical arm of ARTS-I. Nevertheless, existing data suggest that patients with disease of the proximal left anterior descending artery (LAD) may derive particular benefit from coronary artery bypass grafting (CABG). We therefore analysed the clinical outcome of patients in ARTS-I and ARTS-II with proximal LAD involvement. Design: Multicentre observational study. Setting: Forty-five European academic hospitals. Patients: Patients with multivessel coronary artery disease. Interventions: Patients in ARTS-II with proximal LAD disease treated with SES (289/607, 48%) were compared with 187/600 (31%) bare metal stent patients (ARTS-I BMS) and 206/605 (34%) surgical patients (ARTS-I CABG) with proximal LAD involvement from ARTS-I. Main outcome measures: Major adverse cardiac and cerebrovascular events after 3 years. Results: The Arterial Revascularization Therapies study part 2 (ARTS-II) subgroup had better survival than both ARTS-I groups (ARTS-II 98.6% vs ARTS-I BMS 95.7%, p = 0.05 and vs ARTS-I CABG 94.7%, p = 0.01) and lower rates of the hard clinical composite endpoint of death or non-fatal myocardial infarction (ARTS-II 3.1% vs ARTS-I BMS 9.6%, p = 0.002 and vs ARTS-I CABG 9.7%, p = 0.002). Although the ARTS-I CABG patients had a lower need for repeat revascularisation than ARTS-II (5.3% vs 13.1%, p = 0.002), the overall composite adverse event rates (death, myocardial infarction, stroke or any repeat revascularisation) were not significantly different between the ARTS-I CABG and ARTS-II patients (15.0% vs 18.0%, p = 0.4). Conclusions: SES are not inferior to CABG or bare metal stents for the treatment of patients with multivessel coronary disease including involvement of the proximal LAD. http://repub.eur.nl/res/pub/24225/ 2009-06-09T00:00:00Z Antiplatelet therapy with clopidogrel has been shown to reduce major adverse cardiac events in acute coronary syndromes and after percutaneous interventions. This effect is not only due to its anti-platelet effect but also possibly due to an anti-inflammatory effect. The effect of clopidogrel cessation after one year of therapy on markers of inflammation has been investigated in diabetics and showed an increase in platelet aggregation as well as hsCRP and surface P-selectin levels. This was an exploratory multicenter prospective open-label single arm study of 98 non-diabetic patients who had received one or more drug eluting stents and were coming to the end of their 12 months course of clopidogrel therapy. The effect of clopidogrel cessation on expression of biomarkers: sCD40L, soluble P-selectin and hsCRP was measured right before clopidogrel cessation (day 0), and subsequently at 1, 2, 3 and 4 weeks after drug withdrawal. A median increase in sCD40L expression from 224 to 324.5 pg/ml was observed between baseline and 4 weeks after clopidogrel cessation, which corresponded to a 39% mean percent change based on an ANCOVA model (P < 0.001). Over the 4 weeks observation period the change in sCD40L expression correlated weakly with soluble P-selectin levels (at 4 weeks Spearman's correlation coefficient = 0.32; P = 0.0024). Increase in P-selectin expression from baseline was statistically significant at week 1 and 2. Conversely, hsCRP level decreased by 21% at 1 week (P = 0.008) and was still reduced by 18% by 4 weeks (P = 0.062). The change in sCD40L expression appeared to vary with the type of drug eluting stent. Patients treated with drug eluting stents at 1 year after implantation display significant increase in sCD40L and decrease in hsCRP after clopidogrel cessation. Further studies should elucidate if this increase in sCD40L levels reflects solely the removal of the inhibitory effects of clopidogrel on platelet activity or rather an increase in pro-inflammatory state. The latter hypothesis may be less likely given decrease in hsCRP levels. Randomized studies are urgently needed to establish potential link of clopidogrel discontinuation and vascular outcomes. http://repub.eur.nl/res/pub/24418/ 2009-05-01T00:00:00Z Objectives: This study explored whether an individual or a cluster of risk factors affects the extent of necrotic core (NC) assessed by intravascular ultrasound (IVUS) radiofrequency data (RFD) analysis. Background: Several systemic diseases contribute to the development of coronary artery disease. Methods: The Global Intravascular Radiofrequency Data Analysis Registry was a prospective, multicenter, nonrandomized database that enrolled 990 patients with coronary artery disease in whom 1 major coronary artery was imaged by IVUS-RFD. For the multivariable analysis, the population was divided into 4 classes: young women, young men (both ≤62 years), old women, and old men (>62 years). Mean NC area was categorized as 1: top quartile (≥0.62 mm2) or as 0: lower 3 quartiles. Results: Young patients had less NC compared with older patients (0.40 ± 0.36 mm2of NC vs. 0.50 ± 0.46 mm2in old patients, p = 0.0007). Nondiabetic patients had less NC than diabetic patients (0.43 ± 0.41 mm2of NC vs. 0.51 ± 0.44 mm2in diabetic patients, p = 0.02). The NC area was lower in normotensive patients (0.40 ± 0.36 mm2) than in hypertensive patients (0.48 ± 0.44 mm2) (p = 0.02). In the bivariate analysis, age, hypertension, diabetes, and prior coronary artery bypass graft were statistically significant, however in logistic regression analysis, only age (odds ratio [OR]: 1.023, 95% confidence interval [CI]: 1.009 to 1.037, p = 0.001) and diabetes (OR: 1.636, 95% CI: 1.174 to 2.279, p = 0.004) remained statistically significant. In a per-class logistic regression analyses including only diabetes as covariate, the OR in young women was 2.1 (95% CI: 0.77 to 6.0, p = 0.14), in young men the OR was 1.6 (95% CI: 0.90 to 2.7, p = 0.11), in old women the OR was 2.3 (95% CI: 1.09 to 4.9, p = 0.03), and in old men the OR was 1.6 (95% CI: 0.96 to 2.7, p = 0.07). Further, when only patients with diabetes and hypertension were included, young men (OR: 2.0, p = 0.041), old women (OR: 3.04, p = 0.046), and old men (OR: 2.2, p = 0.025) were significant. Conclusions: Individually and collectively, age and diabetes mellitus are associated with an increase in NC by IVUS-RFD analysis. http://repub.eur.nl/res/pub/29780/ 2008-12-09T00:00:00Z Objectives: The purpose of this study was to assess the 3-year outcome of coronary artery bypass graft surgery (CABG) and percutaneous coronary intervention (PCI) using sirolimus-eluting stents (SES) in patients who had multivessel coronary artery disease with and without diabetes mellitus. Background: The optimal method of revascularization in diabetic patients remains in dispute. Methods: The ARTS-II (Arterial Revascularization Therapies Study-Part II) trial is a single-arm study (n = 607) that included 159 diabetic patients treated with SES whose 3-year clinical outcome was compared with that of the historical diabetic and nondiabetic arms of the randomized ARTS-I trial (n = 1,205, including 96 diabetic patients in the CABG arm and 112 in the PCI arm). Results: At 3 years, among nondiabetic patients, the incidence of the primary composite of death, CVA, myocardial infarction (MI), and repeat revascularization (major adverse cardiac and cerebrovascular events [MACCE]), was significantly lower in ARTS-II than in ARTS-I PCI (adjusted odds ratio [OR]: 0.41; 95% confidence interval [CI]: 0.26 to 0.64) and similar to ARTS-I CABG. The ARTS-II patients were at significantly lower risk for death, CVA, and MI as compared with both the ARTS-I PCI (adjusted OR: 0.55; 95% CI: 0.34 to 0.91) and ARTS-I CABG patients (adjusted OR: 0.56; 95% CI: 0.35 to 0.92). Among diabetic patients, the incidence of MACCE in ARTS-II was similar to that of both PCI and CABG in ARTS-I. Conversely, the incidence of death, CVA, and MI was significantly lower in ARTS-II than in ARTS-I PCI (adjusted OR: 0.67; 95% CI: 0.27 to 1.65) and was similar to that of ARTS-I CABG. Conclusions: At 3 years, PCI using SES for patients with multivessel coronary artery disease seems to be safer and more efficacious than PCI using bare-metal stents, irrespective of the diabetic status of the patient. Hence, PCI using SES appears to be a valuable alternative to CABG for both diabetic and nondiabetic patients. http://repub.eur.nl/res/pub/35528/ 2007-03-15T00:00:00Z According to pathologic studies, the content of a necrotic core increases in a "linear fashion" as plaque enlarges. In addition, these 2 plaque characteristics have been associated with plaque vulnerability. This study assessed the relation between plaque cross-sectional area (CSA) and content of necrotic core (NC). Twenty-five patients (75 arteries) with acute coronary syndrome were studied. In total, 7,834 CSAs were analyzed. An analysis of plaque CSA in percentiles was performed (median 5.5 mm2, interquartile range 3.7 to 7.8); subsequently, plaque CSA values were categorized as small (≤3.7 mm2), medium (>3.7 to ≤7.8 mm2), and large (>7.8 mm2). There was a difference in content of the NC between arteries within each plaque CSA category. This observation was confirmed in a multivariate analysis in which only 2 variables remained statistically significant, plaque CSA (estimate 1.34, SE 0.05, p <0.0001) and studied artery (left anterior descending coronary artery, estimate 0.29, SE 0.08, p = 0.0003; left circumflex coronary artery, estimate 0.23, SE 0.07, p = 0.0014; and these vs the right coronary artery). In conclusion, the NC and plaque increase in patients with acute coronary syndromes. http://repub.eur.nl/res/pub/13314/ 2004-03-23T00:00:00Z BACKGROUND: The factors associated with the occurrence of restenosis after sirolimus-eluting stent (SES) implantation in complex cases are currently unknown. METHODS AND RESULTS: A cohort of consecutive complex patients treated with SES implantation was selected according to the following criteria: (1) treatment of acute myocardial infarction, (2) treatment of in-stent restenosis, (3) 2.25-mm diameter SES, (4) left main coronary stenting, (5) chronic total occlusion, (6) stented segment >36 mm, and (7) bifurcation stenting. The present study population was composed of 238 patients (441 lesions) for whom 6-month angiographic follow-up data were obtained (70% of eligible patients). Significant clinical, angiographic, and procedural predictors of post-SES restenosis were evaluated. Binary in-segment restenosis was diagnosed in 7.9% of lesions (6.3% in-stent, 0.9% at the proximal edge, 0.7% at the distal edge). The following characteristics were identified as independent multivariate predictors: treatment of in-stent restenosis (OR 4.16, 95% CI 1.63 to 11.01; P<0.01), ostial location (OR 4.84, 95% CI 1.81 to 12.07; P<0.01), diabetes (OR 2.63, 95% CI 1.14 to 6.31; P=0.02), total stented length (per 10-mm increase; OR 1.42, 95% CI 1.21 to 1.68; P<0.01), reference diameter (per 1.0-mm increase; OR 0.46, 95% CI 0.24 to 0.87; P=0.03), and left anterior descending artery (OR 0.30, 95% CI 0.10 to 0.69; P<0.01). CONCLUSIONS: Angiographic restenosis after SES implantation in complex patients is an infrequent event, occurring mainly in association with lesion-based characteristics and diabetes mellitus. http://repub.eur.nl/res/pub/8304/ 2004-01-01T00:00:00Z AIMS: To investigate the effect on risk of major adverse cardiac events (MACE) of lipid lowering treatment with fluvastatin 80 mg/day after a first percutaneous coronary intervention in patients with stable and unstable angina. METHOD AND RESULTS: This prespecified subgroup analysis of the LIPS (Lescol intervention prevention study) analysed 1658 patients with documented diagnosis; 824 had unstable angina (417 randomly assigned to fluvastatin, 407 to placebo) and 834 had stable angina (including silent ischaemia; fluvastatin, 418; placebo, 416). Median follow up was 3.9 years. There was no significant effect of anginal status on long term risk of MACE. Fluvastatin treatment reduced the risk of MACE by 28% compared with placebo (p = 0.03) among patients with unstable angina, with no difference between patients with stable and patients with unstable angina (relative risk 1.07, 95% confidence interval 0.87 to 1.30, p = 0.53). Fluvastatin reduced coronary atherosclerotic events (MACE excluding restenosis) by 36% (p = 0.006) among patients with unstable angina and 31% (p = 0.02) among patients with stable angina. Fluvastatin caused similar reductions in total cholesterol and low density lipoprotein cholesterol concentrations in both patient groups. CONCLUSION: Treatment with fluvastatin 80 mg/day produced significant reductions in MACE and coronary atherosclerotic events after percutaneous coronary intervention in patients with average cholesterol concentrations. The beneficial effects of fluvastatin are observed in patients with unstable or stable angina alike.